Bladder Cancer

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Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"


Condition: Upper Tract Urothelial Carcinoma

Intervention:

  • Procedure: RNU
  • Drug: Gemcitabine/Cisplatin
  • Drug: M-VAC Protocol

Purpose: The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC) treatments based in real world data in various European countries. The study will allow to gain insight in the true proportion of patients that fit to receive complete cisplatin-based neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients with poor prognostic factors (PS and renal function) who receive only standard treatment (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic and treatment protocol.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02969083

Sponsor: The European Uro-Oncology Group

Primary Outcome Measures:

  • Measure: Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
  • Time Frame: 6 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Disease Free Survival (DFS)
  • Time Frame: 1-2 years
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: 1-2 years
  • Safety Issue:
  • Measure: Cancer-Specific Survival (CSS)
  • Time Frame: 1-2 years
  • Safety Issue:

Estimated Enrollment: 210

Study Start Date: May 28, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Written informed consent
  • Age > 18 years
  • Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification)
  • Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception
  • Patients without bladder cancer or with concomitant non muscle invasive bladder cancer
  • Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF 55 ml/min: Electrolytes: potassium, magnesium and calcium: within normal limits.
  • CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis Exclusion Criteria:
  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
  • History of cardiovascular conditions within the past 6 months.
  • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an

Exclusion Criteria:

  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
  • History of cardiovascular conditions within the past 6 months.
  • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment.
  • Any major contraindication to a surgical procedure.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Active infection contraindicating chemotherapy
  • Concomitant diseases that are a formal exclusion to platinum-based chemotherapy (deafness, grade II neuropathy).
  • Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, Prostate specific antigen (PSA) <10. Patients with past medical history of cancer can be included if diagnosed at least 5 years ago.
  • Concomitant muscle invasive bladder cancer
  • Patients who have been or still are on methotrexate treatment.

Contact:

  • Cristina Alvarez, MSc, PhD
  • +31(0)715264109

Location:

  • Leiden University Medical Centre
  • Leiden South Holland Netherlands

View trial on ClinicalTrials.gov


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Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing


Condition: Bladder Cancer

Intervention:

  • Drug: Nivolumab
  • Drug: Gemcitabine
  • Drug: Cisplatin

Purpose: This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03558087

Sponsor: Matthew Galsky

Primary Outcome Measures:

  • Measure: Determine the clinical complete response rate (cT0 or cTa) with gemcitabine, cisplatin, plus nivolumab
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.
  • Time Frame: 24 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Assess Adverse Events
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Bladder intact overall survival
  • Time Frame: 24 Months
  • Safety Issue:
  • Measure: Recurrence-free survival
  • Time Frame: 24 months
  • Safety Issue:
  • Measure: Pathologic complete response rate in patients undergoing cystectomy
  • Time Frame: 24 Months
  • Safety Issue:
  • Measure: Determine the association between a prespecified panel of genomic biomarkers and benefit from treatment in patients achieving a clinical complete response.
  • Time Frame: 24 months
  • Safety Issue:

Estimated Enrollment: 63

Study Start Date: July 13, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • ECOG Performance Status of ≤ 1 within 28 days prior to registration.
  • Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder (i.e., ct2-4n0m0). candidate for cystectomy as per treating physician.
  • Demonstrate adequate organ function per listed criteria:
  • Absolute Neutrophil Count (ANC): ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb): ≥ 9 g/dL
  • Platelets: ≥ 100 x 10^9/L
  • Calculated creatinine clearance: Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) : ≤ 3 × ULN
  • Alanine aminotransferase (ALT) : ≤ 3 × ULN
  • All subjects must have adequate archival tissue submitted prior to registration (i.e., at least 15 unstained slides or paraffin block).
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.
  • Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to C1D1.
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy for muscle-invasive urothelial cancer of the bladder
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Grade ≥ 2 neuropathy (NCI CTCAE version 4).
  • Prior radiation therapy for bladder cancer
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Solid organ or allogeneic stem cell transplant

Contact:

  • Matthew Galsky, MD
  • 212-659-5599

Location:

  • Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center
  • New York New York 10029 United States

View trial on ClinicalTrials.gov


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A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy


Condition: Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B, Bladder Cancer TNM Staging Regional Lymph Node (N) N0, Bladder Cancer TNM Staging Regional Lymph Node (N) N1, Bladder Cancer TNM Staging Distant Metastasis (M) M0

Intervention:

  • Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200
  • Drug: Nivolumab Injection [Opdivo]

Purpose: The purpose of this study is to determine if TAR-200, an investigational drug delivery system, in combination with nivolumab is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) during an 84-day dosing cycle induction period comprised of four consecutive 21-day dosing cycles.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03518320

Sponsor: Taris Biomedical LLC

Primary Outcome Measures:

  • Measure: Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 in combination with Nivolumab as assessed by CTCAE V4.0.
  • Time Frame: Study Day 0 to Study Day 180
  • Safety Issue:
  • Measure: Number of participants that do not require treatment discontinuation prior to the scheduled end date due to meeting any of the Subject Stopping Safety criteria or other drug or device related AE
  • Time Frame: Study Day 0 to Study Day 180
  • Safety Issue:

Estimated Enrollment: 25

Study Start Date: November 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed. 2. Subjects with a total tumor size of ≤2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ≤2 cm to be eligible for treatment. 3. Adequate bone marrow, liver, and renal function, as documented by the following laboratory assessments conducted within 28 days prior to dosing:
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count (ANC) ≥1,500/mm3
  • Platelet count ≥100,000/mm3
  • Total bilirubin ≤1.5x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN
  • Glomerular filtration rate (GFR) ≥30 ml/min/1.73 m2 (assessed using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) 4. Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination. 5. Deemed eligible for and willing to undergo RC by the attending urologist. 6. Subjects must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
  • GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
  • Common Terminology Criteria for Adverse Events (CTCAE) v4 Grade ≥2 audiometric hearing loss
  • CTCAE v4 Grade ≥2 peripheral neuropathy 7. Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (National Cancer Institute CTCAE version 4.03) or baseline before administration of study drug. Participants with toxicities attributed to prior anti cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are permitted to enroll. 8. Written informed consent and authorization for release of personal health information obtained according to local laws. 9. Age ≥18 years at the time of consent. 10. Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception (hormonal or intrauterine device [IUD] method of birth control with a failure rate of <1% when used consistently and correctly; or abstinence) for the duration of treatment with TAR-200 in combination with nivolumab plus 5 half-lives of study treatment, plus 30 days (duration of ovulatory cycle), for a total of 5 months post treatment completion. Note: WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this protocol. 11. WOCBP must have a negative pregnancy test within 24 hours prior to Study Day 0. 12. Males must be willing to use an effective method of contraception to avoid seminal transfer (double barrier method) or abstinence for the duration of treatment with TAR 200 in combination with nivolumab plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover), for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. 13. Azoospermic males should also use double barrier contraceptive methods to avoid contamination of the non-treatment sexual partner. Exclusion Criteria: 1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome. 2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder. 3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways. 4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis. 5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 200. 8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder. 9. Indwelling catheters are not permitted. 10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing. 11. Bladder post-void residual volume of >500 mL. 12. History of diagnosis of neurogenic bladder requiring intermittent catheterization. 13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study. 14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection. 15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally. 16. Uncontrolled adrenal insufficiency. 17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1). 18. Eastern Cooperative Oncology Group (ECOG) performance status ≥2. 19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. 20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation. 21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. 22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day 0. 23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine. 24. History of allergy or hypersensitivity to the device constituent or Inserter materials. 25. History of allergy or hypersensitivity to nivolumab drug components. 26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception. 27. Difficulty providing blood samples. 28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0. 30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.) 31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/

Exclusion Criteria:

  1. Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome.
  2. Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
  3. Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
  4. Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
  5. Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  6. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  7. Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 2
  8. Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder.
  9. Indwelling catheters are not permitted.
  10. Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing.
  11. Bladder post-void residual volume of >500 mL.
  12. History of diagnosis of neurogenic bladder requiring intermittent catheterization.
  13. Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
  14. Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  15. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally.
  16. Uncontrolled adrenal insufficiency.
  17. New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1).
  18. Eastern Cooperative Oncology Group (ECOG) performance status ≥
  19. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
  20. Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
  21. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  22. Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day
  23. History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine.
  24. History of allergy or hypersensitivity to the device constituent or Inserter materials.
  25. History of allergy or hypersensitivity to nivolumab drug components.
  26. Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception.
  27. Difficulty providing blood samples.
  28. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  29. Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day
  30. Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.)
  31. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness Other protocol defined inclusion/exclusion criteria could apply.

Contact:

  • TARIS Biomedical LLC
  • +1-781-676-7750

Locations:

  • DuPage Medical Group
  • Hinsdale Illinois 60521 United States
  • University of Rochester Medical Center
  • Rochester New York 14642 United States
  • Duke University Medical Center
  • Durham North Carolina 27710 United States
  • The University of Oklahoma Stephenson Cancer Center
  • Oklahoma City Oklahoma 73104 United States
  • Thomas Jefferson University
  • Philadelphia Pennsylvania 19107 United States
  • Vanderbilt University Medical Center
  • Nashville Tennessee 37232 United States

View trial on ClinicalTrials.gov


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Phase II Study of Pembrolizumab (MK-3475) as First-Line Therapy for High Risk T1 Non-Muscle-Invasive Bladder Cancer


Condition: Bladder Cancer

Intervention:

  • Drug: Pembrolizumab (MK-3475)

Purpose: The purpose of this study is to find out what effects, good and/or bad, pembrolizumab has on the participant and urothelial cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03504163

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

  • Measure: The proportion of patients who are disease-free
  • Time Frame: 6 months
  • Safety Issue:

Estimated Enrollment: 37

Study Start Date: June 27, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial.
  • Histologically confirmed urothelial cancer by TURBT performed at MSKCC.
  • TURBT within 6 weeks of protocol entry with complete resection of all papillary lesions.
  • Patients with high risk, BCG-naïve non-muscle-invasive urothelial cancer defined as having one of the following disease states:
  • T1 on restaging biopsy, plus cis
  • Multiple (≥ 1) T1 recurrences, plus cis
  • Multifocal T1 plus cis
  • T1b, plus cis
  • T1 with lymphovascular invasion plus cis
  • Patient refusal of cystectomy and bilateral pelvic lymphadenectomy
  • No prior intravesical therapy.
  • No prior radiation therapy for bladder cancer. Prior radiation therapy for prostate cancer is allowed.
  • ECOG performance status 0 or 1.
  • Age ≥ 18 years of age
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of the study medication (reference section 9.5.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Patients must not have other invasive malignancies within the past 5 years (with the exception of non-melanoma skin cancers, localized prostate cancer, and carcinoma in situ of the cervix).
  • Required Initial Laboratory Values:
  • Absolute neutrophil count ≥ 1.5 x 10E9/L
  • Platelets ≥ 100 x 10E9/L
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 times the upper limit of normal (x ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN
  • Calculated creatinine clearance ≥ 30 using the CKD-Epi formula

Exclusion Criteria:

  • Prior treatment with systemic chemotherapy
  • Unstable angina
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • History of myocardial infarction within 6 months
  • History of stroke within 6 months
  • Evidence of bleeding diathesis or coagulopathy
  • Presence of any systemic metastases (ie, nodal, visceral, or central nervous system)
  • Major surgical procedure (other than TURBT) within 28 days prior to the study
  • Pregnant (positive pregnancy test) or lactating
  • Serious, non-healing wound, ulcer, or bone fracture
  • Inability to comply with study and/or follow-up procedures
  • Prior therapy with an anti-PD-1 agent, anti-PD-L1 agent, or other inhibitory or stimulatory agent oriented towards a T-cell receptor
  • Active infection requiring systemic therapy
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or Hepatitis C
  • Received live attenuated vaccines within 30 days prior to start of study treatment. Patients must also agree to avoid live attenuated vaccines during study treatment.
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents. Subjects with vitiligo, diabetes Type I, or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjøgren's syndrome will not be excluded from the study.

Contact:

  • Dean Bajorin, MD
  • 646-422-4333

Location:

  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States

View trial on ClinicalTrials.gov


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An Open-Label, Multi-Center Trial of INO-5401 + INO-9012 in Combination With Atezolizumab in Subjects With Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma


Condition: Urothelial Carcinoma

Intervention:

  • Biological: INO-5401
  • Biological: INO-9012
  • Drug: Atezolizumab
  • Device: CELLECTRA® 2000

Purpose: This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of INO-5401 + INO-9012 delivered by intramuscular (IM) injection followed by electroporation (EP), in combination with atezolizumab in participants with locally advanced unresectable or metastatic/recurrent Urothelial Carcinoma (UCa). The trial population is divided into two cohorts: Cohort A: Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with anti-Programmed Death receptor-1/Programmed Death receptor Ligand-1 (anti-PD-1/PD-L1) therapy; Cohort B: Participants with locally advanced unresectable or metastatic/recurrent UCa, who are treatment naïve and ineligible for cisplatin-based chemotherapy. A safety run-in will be performed with up to six participants (safety analysis participants) from cohort A.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03502785

Sponsor: Inovio Pharmaceuticals

Primary Outcome Measures:

  • Measure: Number of Adverse Events
  • Time Frame: From baseline up to 90 days after last dose of study medication (up to approximately 2 years and 3 months)
  • Safety Issue:
  • Measure: Antigen-Specific Cellular Immune Response
  • Time Frame: At baseline, Weeks 3, 6, 9, 12 and every 12 weeks thereafter up to end of study (up to approximately 2 years)
  • Safety Issue:
  • Measure: Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator Review in Cohort A
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: ORR by RECIST version 1.1 by Investigator Review in Cohort B
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: ORR by Immune RECIST (iRECIST)
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Duration of Response (DoR)
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Progression Free Survival (PFS) as Assessed by RECIST version 1.1 and iRECIST
  • Time Frame: From Baseline to disease progression or death, whichever occurs first (up to approximately 2 years)
  • Safety Issue:
  • Measure: Overall Survival (OS)
  • Time Frame: : From Baseline to the time of death from any cause (up to approximately 2 years)
  • Safety Issue:

Estimated Enrollment: 85

Study Start Date: May 24, 2018

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Sign an Informed Consent Form (ICF);
  • Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
  • For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy;
  • For Cohort B: No prior chemotherapy for inoperable locally advanced or metastatic or recurrent UCa and ineligible ("unfit") for cisplatin-based chemotherapy;
  • Have measurable disease, as defined by RECIST version 1.1;
  • Have a performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Performance Scale;
  • Have life expectancy of >/= 3 months;
  • Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of proinflammatory and immunosuppressive factors;
  • Have electrocardiogram (ECG) with no clinically significant findings as assessed by the investigator performed within 28 days prior to first dose;
  • Demonstrate adequate hematological, renal, hepatic, and coagulation function;
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment;
  • For male subjects: agreement not to father a child. Participants must be surgically sterile (e.g, vasectomy) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of study treatment.

Exclusion Criteria:

  • Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0 as well as current participation or recipient of treatment on a clinical trial within 28 days prior to Day 0;
  • Documented active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis;
  • Malignancies other than UCa within 3 years prior to Day 0, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome;
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies;
  • Treatment with systemic immunostimulatory agents;
  • Treatment with systemic immunosuppressive medication;
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
  • Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation;
  • Active or history of autoimmune disease or immune deficiency;
  • History or any evidence of interstitial lung disease;
  • History of human immunodeficiency virus (HIV);
  • Active hepatitis B or active hepatitis C;
  • Severe infections within 4 weeks prior to enrollment;
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0;
  • History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the trial; interfere with the subject's participation for the full duration of the trial, or is negatively impacted by EP treatment, or is not in the best interest of the subject to participate in the opinion of the treating investigator;
  • Prior allogeneic stem cell or solid organ transplant;
  • Uncontrolled tumor-related pain; pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures; or, hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.

Contact:

  • Inovio Call Center
  • 267-440-4237

Locations:

  • Alaska Clinical Research Center, LLC
  • Anchorage Alaska 99503 United States
  • Clinical Trials Office - All Mayo Clinic Locations
  • Tucson Arizona 85724 United States
  • H. Lee Moffitt Cancer Center & Research Institute, Inc.
  • Tampa Florida 33612 United States
  • Indiana University Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • Johns Hopkins University School of Medicine
  • Baltimore Maryland 21287 United States
  • Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Washington University School of Medicine in St. Louis
  • Saint Louis Missouri 63110 United States
  • New York University Langone Medical Center - Perlmutter Cancer Center
  • New York New York 10016 United States
  • Columbia University, Herbert Irving Comprehensive Cancer Center
  • New York New York 10032 United States
  • University of North Carolina School of Medicine
  • Chapel Hill North Carolina 27599 United States
  • University of Pittsburgh Medical Center
  • Pittsburgh Pennsylvania 15232 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29615 United States
  • Inova Melanoma and Skin Cancer Center
  • Fairfax Virginia 22031 United States
  • Hospital de la Santa Creu i Sant Pau
  • Barcelona 08025 Spain
  • Hospital Universitario 12 de Octubre
  • Madrid 28041 Spain
  • Centro Integral Oncológico Clara Campal (CIOCC)
  • Madrid 28050 Spain

View trial on ClinicalTrials.gov


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A Phase II Study of Dose-Dense Gemcitabine Plus Cisplatin (ddGC) in Patients With Muscle-Invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations


Condition: Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma

Intervention:

  • Drug: Gemcitabine Hydrochloride
  • Drug: Cisplatin
  • Biological: Pegfilgrastim
  • Procedure: Conventional Surgery
  • Procedure: Radical Cystectomy
  • Other: Chemoradiotherapy

Purpose: This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03609216

Sponsor: Alliance for Clinical Trials in Oncology

Primary Outcome Measures:

  • Measure: Proportion of patients who are recurrence-free within the DDR mutated group who undergo the bladder sparing approach
  • Time Frame: At 3 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Clinical response rate for patients harboring deleterious DDR gene alterations
  • Time Frame: After 6 courses (84 days)
  • Safety Issue:
  • Measure: Bladder-intact survival in DDR-altered patients with < cT1 responses who selected the bladder sparing approach
  • Time Frame: Time from registration up to 5 years
  • Safety Issue:
  • Measure: Overall survival
  • Time Frame: Time from study registration up to 5 years
  • Safety Issue:
  • Measure: Pathologic response (pT0) rate at cystectomy in participants without DDR gene alterations
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Recurrence-free survival
  • Time Frame: Time from study registration up to 5 years
  • Safety Issue:
  • Measure: The rate of cystectomies in patients with a DDR alteration and with a cT0/CIS/Ta response
  • Time Frame: Within 3 years
  • Safety Issue:
  • Measure: Proportion of patients in the bladder-sparing group who undergo local therapy
  • Time Frame: Up to 5 years
  • Safety Issue:

Estimated Enrollment: 271

Study Start Date: August 1, 2018

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Step 1 Patient Registration Eligibility Criteria
  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration

Eligibility Criteria:

  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
  • 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
  • Clinical stage T2-T4aN0/xM0 disease
  • Medically appropriate candidate for radical cystectomy as assessed by surgeon
  • No concomitant multifocal carcinoma in situ; a single focus is allowed
  • One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
  • No clinical or radiographic evidence for locally advanced or metastatic disease
  • No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6 treatments; BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed)
  • No prior radiation therapy to the bladder
  • No major surgery or radiation therapy =< 4 weeks of registration
  • Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Calculated creatinine clearance >= 55 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • No hydronephrosis refractory to urinary diversion
  • No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
  • No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
  • No pre-existing sensory grade >= 2 neuropathy
  • No pre-existing grade >= 2 hearing loss
  • No serious intercurrent medical or psychiatric illness, including serious active infection
  • None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
  • No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
  • No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
  • No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
  • Step 2 Patient Registration Eligibility Criteria
  • Patients must have completed 4 or more cycles of protocol-directed chemotherapy
  • Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
  • Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
  • Cystoscopy and imaging performed to determine stage/treatment assignment

Contact:

  • Gopa Iyer, MD
  • 646-888-4737

Locations:

  • CHI Saint Vincent Cancer Center Hot Springs
  • Hot Springs Arkansas 71913 United States
  • Fremont - Rideout Cancer Center
  • Marysville California 95901 United States
  • University of California Davis Comprehensive Cancer Center
  • Sacramento California 95817 United States
  • Penrose-Saint Francis Healthcare
  • Colorado Springs Colorado 80907 United States
  • Rocky Mountain Cancer Centers-Penrose
  • Colorado Springs Colorado 80907 United States
  • Porter Adventist Hospital
  • Denver Colorado 80210 United States
  • Mercy Medical Center
  • Durango Colorado 81301 United States
  • Southwest Oncology PC
  • Durango Colorado 81301 United States
  • Mountain Blue Cancer Care Center
  • Golden Colorado 80401 United States
  • Rocky Mountain Cancer Centers-Lakewood
  • Lakewood Colorado 80228 United States
  • Saint Anthony Hospital
  • Lakewood Colorado 80228 United States
  • Littleton Adventist Hospital
  • Littleton Colorado 80122 United States
  • Longmont United Hospital
  • Longmont Colorado 80501 United States
  • Rocky Mountain Cancer Centers-Longmont
  • Longmont Colorado 80501 United States
  • Parker Adventist Hospital
  • Parker Colorado 80138 United States
  • Rocky Mountain Cancer Centers-Parker
  • Parker Colorado 80138 United States
  • Saint Mary Corwin Medical Center
  • Pueblo Colorado 81004 United States
  • Rocky Mountain Cancer Centers - Pueblo
  • Pueblo Colorado 81008 United States
  • Rocky Mountain Cancer Centers-Thornton
  • Thornton Colorado 80260 United States
  • Saint Alphonsus Cancer Care Center-Boise
  • Boise Idaho 83706 United States
  • Saint Alphonsus Cancer Care Center-Caldwell
  • Caldwell Idaho 83605 United States
  • Kootenai Medical Center
  • Coeur d'Alene Idaho 83814 United States
  • Walter Knox Memorial Hospital
  • Emmett Idaho 83617 United States
  • Idaho Urologic Institute-Meridian
  • Meridian Idaho 83642 United States
  • Saint Alphonsus Medical Center-Nampa
  • Nampa Idaho 83686 United States
  • Kootenai Cancer Center
  • Post Falls Idaho 83854 United States
  • Kootenai Cancer Clinic
  • Sandpoint Idaho 83864 United States
  • Illinois CancerCare-Bloomington
  • Bloomington Illinois 61704 United States
  • Illinois CancerCare-Canton
  • Canton Illinois 61520 United States
  • Memorial Hospital of Carbondale
  • Carbondale Illinois 62902 United States
  • SIH Cancer Institute
  • Carterville Illinois 62918 United States
  • Illinois CancerCare-Carthage
  • Carthage Illinois 62321 United States
  • Centralia Oncology Clinic
  • Centralia Illinois 62801 United States
  • Cancer Care Specialists of Illinois - Decatur
  • Decatur Illinois 62526 United States
  • Decatur Memorial Hospital
  • Decatur Illinois 62526 United States
  • Crossroads Cancer Center
  • Effingham Illinois 62401 United States
  • Illinois CancerCare-Eureka
  • Eureka Illinois 61530 United States
  • Illinois CancerCare-Galesburg
  • Galesburg Illinois 61401 United States
  • Western Illinois Cancer Treatment Center
  • Galesburg Illinois 61401 United States
  • Illinois CancerCare-Kewanee Clinic
  • Kewanee Illinois 61443 United States
  • Illinois CancerCare-Macomb
  • Macomb Illinois 61455 United States
  • Illinois CancerCare-Ottawa Clinic
  • Ottawa Illinois 61350 United States
  • Illinois CancerCare-Pekin
  • Pekin Illinois 61554 United States
  • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
  • Pekin Illinois 61554 United States
  • Illinois CancerCare-Peoria
  • Peoria Illinois 61615 United States
  • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
  • Peoria Illinois 61615 United States
  • Methodist Medical Center of Illinois
  • Peoria Illinois 61636 United States
  • OSF Saint Francis Medical Center
  • Peoria Illinois 61637 United States
  • Illinois CancerCare-Peru
  • Peru Illinois 61354 United States
  • Valley Radiation Oncology
  • Peru Illinois 61354 United States
  • Illinois CancerCare-Princeton
  • Princeton Illinois 61356 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States
  • Springfield Clinic
  • Springfield Illinois 62702 United States
  • Memorial Medical Center
  • Springfield Illinois 62781 United States
  • Cancer Care Specialists of Illinois-Swansea
  • Swansea Illinois 62226 United States
  • Southwest Illinois Health Services LLP
  • Swansea Illinois 62226 United States
  • Reid Health
  • Richmond Indiana 47374 United States
  • Medical Oncology and Hematology Associates-West Des Moines
  • Clive Iowa 50325 United States
  • Mercy Cancer Center-West Lakes
  • Clive Iowa 50325 United States
  • Alegent Health Mercy Hospital
  • Council Bluffs Iowa 51503 United States
  • Greater Regional Medical Center
  • Creston Iowa 50801 United States
  • Iowa Methodist Medical Center
  • Des Moines Iowa 50309 United States
  • Medical Oncology and Hematology Associates-Des Moines
  • Des Moines Iowa 50309 United States
  • Broadlawns Medical Center
  • Des Moines Iowa 50314 United States
  • Medical Oncology and Hematology Associates-Laurel
  • Des Moines Iowa 50314 United States
  • Mercy Medical Center - Des Moines
  • Des Moines Iowa 50314 United States
  • Iowa Lutheran Hospital
  • Des Moines Iowa 50316 United States
  • Trinity Regional Medical Center
  • Fort Dodge Iowa 50501 United States
  • Methodist West Hospital
  • West Des Moines Iowa 50266-7700 United States
  • Mercy Medical Center-West Lakes
  • West Des Moines Iowa 50266 United States
  • Flaget Memorial Hospital
  • Bardstown Kentucky 40004 United States
  • Commonwealth Cancer Center-Corbin
  • Corbin Kentucky 40701 United States
  • Saint Joseph Radiation Oncology Resource Center
  • Lexington Kentucky 40504 United States
  • Saint Joseph Hospital East
  • Lexington Kentucky 40509 United States
  • Saint Joseph London
  • London Kentucky 40741 United States
  • Jewish Hospital
  • Louisville Kentucky 40202 United States
  • Saints Mary and Elizabeth Hospital
  • Louisville Kentucky 40215 United States
  • Jewish Hospital Medical Center Northeast
  • Louisville Kentucky 40245 United States
  • Jewish Hospital Medical Center South
  • Shepherdsville Kentucky 40165 United States
  • East Jefferson General Hospital
  • Metairie Louisiana 70006 United States
  • Louisiana State University Health Science Center
  • New Orleans Louisiana 70112 United States
  • University Medical Center New Orleans
  • New Orleans Louisiana 70112 United States
  • Ochsner Medical Center Jefferson
  • New Orleans Louisiana 70121 United States
  • Mercy Medical Center
  • Springfield Massachusetts 01104 United States
  • Saint Joseph Mercy Hospital
  • Ann Arbor Michigan 48106 United States
  • IHA Hematology Oncology Consultants-Brighton
  • Brighton Michigan 48114 United States
  • Saint Joseph Mercy Brighton
  • Brighton Michigan 48114 United States
  • IHA Hematology Oncology Consultants-Canton
  • Canton Michigan 48188 United States
  • Saint Joseph Mercy Canton
  • Canton Michigan 48188 United States
  • Caro Cancer Center
  • Caro Michigan 48723 United States
  • IHA Hematology Oncology Consultants-Chelsea
  • Chelsea Michigan 48118 United States
  • Saint Joseph Mercy Chelsea
  • Chelsea Michigan 48118 United States
  • Hematology Oncology Consultants-Clarkston
  • Clarkston Michigan 48346 United States
  • Newland Medical Associates-Clarkston
  • Clarkston Michigan 48346 United States
  • Ascension Saint John Hospital
  • Detroit Michigan 48236 United States
  • Great Lakes Cancer Management Specialists-Doctors Park
  • East China Township Michigan 48054 United States
  • Genesee Cancer and Blood Disease Treatment Center
  • Flint Michigan 48503 United States
  • Genesee Hematology Oncology PC
  • Flint Michigan 48503 United States
  • Genesys Hurley Cancer Institute
  • Flint Michigan 48503 United States
  • Hurley Medical Center
  • Flint Michigan 48503 United States
  • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
  • Grosse Pointe Woods Michigan 48236 United States
  • Lymphoma Clinic of Michigan
  • Grosse Pointe Woods Michigan 48236 United States
  • Michigan Breast Specialists-Grosse Pointe Woods
  • Grosse Pointe Woods Michigan 48236 United States
  • Sparrow Hospital
  • Lansing Michigan 48912 United States
  • Hope Cancer Clinic
  • Livonia Michigan 48154 United States
  • Saint Mary Mercy Hospital
  • Livonia Michigan 48154 United States
  • Great Lakes Cancer Management Specialists-Macomb Medical Campus
  • Macomb Michigan 48044 United States
  • Michigan Breast Specialists-Macomb Township
  • Macomb Michigan 48044 United States
  • Saint Mary's Oncology/Hematology Associates of Marlette
  • Marlette Michigan 48453 United States
  • 21st Century Oncology-Pontiac
  • Pontiac Michigan 48341 United States
  • Hope Cancer Center
  • Pontiac Michigan 48341 United States
  • Newland Medical Associates-Pontiac
  • Pontiac Michigan 48341 United States
  • Saint Joseph Mercy Oakland
  • Pontiac Michigan 48341 United States
  • Great Lakes Cancer Management Specialists-Rochester Hills
  • Rochester Hills Michigan 48309 United States
  • Saint Mary's of Michigan
  • Saginaw Michigan 48601 United States
  • Oncology Hematology Associates of Saginaw Valley PC
  • Saginaw Michigan 48604 United States
  • Bhadresh Nayak MD PC-Sterling Heights
  • Sterling Heights Michigan 48312 United States
  • Saint Joseph Health System-Tawas City
  • Tawas City Michigan 48764 United States
  • Advanced Breast Care Center PLLC
  • Warren Michigan 48088 United States
  • Great Lakes Cancer Management Specialists-Macomb Professional Building
  • Warren Michigan 48093 United States
  • Macomb Hematology Oncology PC
  • Warren Michigan 48093 United States
  • Michigan Breast Specialists-Warren
  • Warren Michigan 48093 United States
  • Saint John Macomb-Oakland Hospital
  • Warren Michigan 48093 United States
  • Saint Mary's Oncology/Hematology Associates of West Branch
  • West Branch Michigan 48661 United States
  • Huron Gastroenterology PC
  • Ypsilanti Michigan 48106 United States
  • IHA Hematology Oncology Consultants-Ann Arbor
  • Ypsilanti Michigan 48197 United States
  • Sanford Joe Lueken Cancer Center
  • Bemidji Minnesota 56601 United States
  • Fairview Ridges Hospital
  • Burnsville Minnesota 55337 United States
  • Mercy Hospital
  • Coon Rapids Minnesota 55433 United States
  • Fairview-Southdale Hospital
  • Edina Minnesota 55435 United States
  • Unity Hospital
  • Fridley Minnesota 55432 United States
  • Fairview Maple Grove Medical Center
  • Maple Grove Minnesota 55369 United States
  • Minnesota Oncology Hematology PA-Maplewood
  • Maplewood Minnesota 55109 United States
  • Saint John's Hospital - Healtheast
  • Maplewood Minnesota 55109 United States
  • Abbott-Northwestern Hospital
  • Minneapolis Minnesota 55407 United States
  • Hennepin County Medical Center
  • Minneapolis Minnesota 55415 United States
  • Health Partners Inc
  • Minneapolis Minnesota 55454 United States
  • Monticello Cancer Center
  • Monticello Minnesota 55362 United States
  • New Ulm Medical Center
  • New Ulm Minnesota 56073 United States
  • North Memorial Medical Health Center
  • Robbinsdale Minnesota 55422 United States
  • Park Nicollet Clinic - Saint Louis Park
  • Saint Louis Park Minnesota 55416 United States
  • Regions Hospital
  • Saint Paul Minnesota 55101 United States
  • United Hospital
  • Saint Paul Minnesota 55102 United States
  • Saint Francis Regional Medical Center
  • Shakopee Minnesota 55379 United States
  • Lakeview Hospital
  • Stillwater Minnesota 55082 United States
  • Sanford Thief River Falls Medical Center
  • Thief River Falls Minnesota 56701 United States
  • Ridgeview Medical Center
  • Waconia Minnesota 55387 United States
  • Rice Memorial Hospital
  • Willmar Minnesota 56201 United States
  • Minnesota Oncology Hematology PA-Woodbury
  • Woodbury Minnesota 55125 United States
  • Sanford Cancer Center Worthington
  • Worthington Minnesota 56187 United States
  • Fairview Lakes Medical Center
  • Wyoming Minnesota 55092 United States
  • Parkland Health Center-Bonne Terre
  • Bonne Terre Missouri 63628 United States
  • Saint Francis Medical Center
  • Cape Girardeau Missouri 63703 United States
  • Southeast Cancer Center
  • Cape Girardeau Missouri 63703 United States
  • Siteman Cancer Center at West County Hospital
  • Creve Coeur Missouri 63141 United States
  • Capital Region Southwest Campus
  • Jefferson City Missouri 65109 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Siteman Cancer Center-South County
  • Saint Louis Missouri 63129 United States
  • Missouri Baptist Medical Center
  • Saint Louis Missouri 63131 United States
  • Sainte Genevieve County Memorial Hospital
  • Sainte Genevieve Missouri 63670 United States
  • Missouri Baptist Sullivan Hospital
  • Sullivan Missouri 63080 United States
  • Missouri Baptist Outpatient Center-Sunset Hills
  • Sunset Hills Missouri 63127 United States
  • Community Hospital of Anaconda
  • Anaconda Montana 59711 United States
  • Billings Clinic Cancer Center
  • Billings Montana 59101 United States
  • Bozeman Deaconess Hospital
  • Bozeman Montana 59715 United States
  • Benefis Healthcare- Sletten Cancer Institute
  • Great Falls Montana 59405 United States
  • Great Falls Clinic
  • Great Falls Montana 59405 United States
  • Saint Peter's Community Hospital
  • Helena Montana 59601 United States
  • Kalispell Regional Medical Center
  • Kalispell Montana 59901 United States
  • Community Medical Hospital
  • Missoula Montana 59804 United States
  • CHI Health Saint Francis
  • Grand Island Nebraska 68803 United States
  • Heartland Hematology and Oncology
  • Kearney Nebraska 68845 United States
  • CHI Health Good Samaritan
  • Kearney Nebraska 68847 United States
  • Saint Elizabeth Regional Medical Center
  • Lincoln Nebraska 68510 United States
  • Alegent Health Immanuel Medical Center
  • Omaha Nebraska 68122 United States
  • Hematology and Oncology Consultants PC
  • Omaha Nebraska 68122 United States
  • Alegent Health Bergan Mercy Medical Center
  • Omaha Nebraska 68124 United States
  • Alegent Health Lakeside Hospital
  • Omaha Nebraska 68130 United States
  • Creighton University Medical Center
  • Omaha Nebraska 68131 United States
  • Midlands Community Hospital
  • Papillion Nebraska 68046 United States
  • Englewood Hospital and Medical Center
  • Englewood New Jersey 07631 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Southeastern Medical Oncology Center-Clinton
  • Clinton North Carolina 28328 United States
  • Southeastern Medical Oncology Center-Goldsboro
  • Goldsboro North Carolina 27534 United States
  • Wayne Memorial Hospital
  • Goldsboro North Carolina 27534 United States
  • Onslow Memorial Hospital
  • Jacksonville North Carolina 28546 United States
  • Southeastern Medical Oncology Center-Jacksonville
  • Jacksonville North Carolina 28546 United States
  • Sanford Bismarck Medical Center
  • Bismarck North Dakota 58501 United States
  • Sanford South University Medical Center
  • Fargo North Dakota 58103 United States
  • Sanford Medical Center Fargo
  • Fargo North Dakota 58104 United States
  • Roger Maris Cancer Center
  • Fargo North Dakota 58122 United States
  • Sanford Broadway Medical Center
  • Fargo North Dakota 58122 United States
  • Indu and Raj Soin Medical Center
  • Beavercreek Ohio 45431 United States
  • Dayton Physicians LLC-Miami Valley South
  • Centerville Ohio 45459 United States
  • Miami Valley Hospital South
  • Centerville Ohio 45459 United States
  • Good Samaritan Hospital - Cincinnati
  • Cincinnati Ohio 45220 United States
  • Oncology Hematology Care Inc-Kenwood
  • Cincinnati Ohio 45236 United States
  • Bethesda North Hospital
  • Cincinnati Ohio 45242 United States
  • TriHealth Cancer Institute-Westside
  • Cincinnati Ohio 45247 United States
  • TriHealth Cancer Institute-Anderson
  • Cincinnati Ohio 45255 United States
  • Good Samaritan Hospital - Dayton
  • Dayton Ohio 45406 United States
  • Miami Valley Hospital
  • Dayton Ohio 45409 United States
  • Dayton Physicians LLC-Samaritan North
  • Dayton Ohio 45415 United States
  • Miami Valley Hospital North
  • Dayton Ohio 45415 United States
  • Armes Family Cancer Center
  • Findlay Ohio 45840 United States
  • Blanchard Valley Hospital
  • Findlay Ohio 45840 United States
  • Orion Cancer Care
  • Findlay Ohio 45840 United States
  • Atrium Medical Center-Middletown Regional Hospital
  • Franklin Ohio 45005-1066 United States
  • Dayton Physicians LLC-Atrium
  • Franklin Ohio 45005 United States
  • Dayton Physicians LLC-Wayne
  • Greenville Ohio 45331 United States
  • Wayne Hospital
  • Greenville Ohio 45331 United States
  • Greater Dayton Cancer Center
  • Kettering Ohio 45409 United States
  • First Dayton Cancer Care
  • Kettering Ohio 45420 United States
  • Kettering Medical Center
  • Kettering Ohio 45429 United States
  • Springfield Regional Cancer Center
  • Springfield Ohio 45504 United States
  • Springfield Regional Medical Center
  • Springfield Ohio 45505 United States
  • Dayton Physicians LLC-Upper Valley
  • Troy Ohio 45373 United States
  • Upper Valley Medical Center
  • Troy Ohio 45373 United States
  • University of Oklahoma Health Sciences Center
  • Oklahoma City Oklahoma 73104 United States
  • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Tulsa Oklahoma 74146 United States
  • Saint Alphonsus Medical Center-Baker City
  • Baker City Oregon 97814 United States
  • Saint Alphonsus Medical Center-Ontario
  • Ontario Oregon 97914 United States
  • Lehigh Valley Hospital-Cedar Crest
  • Allentown Pennsylvania 18103 United States
  • Lehigh Valley Hospital - Muhlenberg
  • Bethlehem Pennsylvania 18017 United States
  • Pocono Medical Center
  • East Stroudsburg Pennsylvania 18301 United States
  • Lehigh Valley Hospital-Hazleton
  • Hazleton Pennsylvania 18201 United States
  • Greenville Health System Cancer Institute-Laurens
  • Clinton South Carolina 29325 United States
  • Greenville Health System Cancer Institute-Easley
  • Easley South Carolina 29640 United States
  • Greenville Health System Cancer Institute-Butternut
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Faris
  • Greenville South Carolina 29605 United States
  • Greenville Memorial Hospital
  • Greenville South Carolina 29605 United States
  • Greenville Health System Cancer Institute-Eastside
  • Greenville South Carolina 29615 United States
  • Greenville Health System Cancer Institute-Greer
  • Greer South Carolina 29650 United States
  • Greenville Health System Cancer Institute-Seneca
  • Seneca South Carolina 29672 United States
  • Greenville Health System Cancer Institute-Spartanburg
  • Spartanburg South Carolina 29307 United States
  • Sanford Cancer Center Oncology Clinic
  • Sioux Falls South Dakota 57104 United States
  • Sanford USD Medical Center - Sioux Falls
  • Sioux Falls South Dakota 57117-5134 United States
  • Memorial Hospital
  • Chattanooga Tennessee 37404 United States
  • Pulmonary Medicine Center of Chattanooga-Hixson
  • Hixson Tennessee 37343 United States
  • Memorial GYN Plus
  • Ooltewah Tennessee 37363 United States
  • Saint Joseph Regional Cancer Center
  • Bryan Texas 77802 United States
  • Harrison HealthPartners Hematology and Oncology-Bremerton
  • Bremerton Washington 98310 United States
  • Harrison Medical Center
  • Bremerton Washington 98310 United States
  • Highline Medical Center-Main Campus
  • Burien Washington 98166 United States
  • Saint Elizabeth Hospital
  • Enumclaw Washington 98022 United States
  • Saint Francis Hospital
  • Federal Way Washington 98003 United States
  • Saint Clare Hospital
  • Lakewood Washington 98499 United States
  • Harrison HealthPartners Hematology and Oncology-Poulsbo
  • Poulsbo Washington 98370 United States
  • Franciscan Research Center-Northwest Medical Plaza
  • Tacoma Washington 98405 United States
  • Northwest Medical Specialties PLLC
  • Tacoma Washington 98405 United States
  • United Hospital Center
  • Bridgeport West Virginia 26330 United States
  • WVUH-Berkely Medical Center
  • Martinsburg West Virginia 25401 United States
  • West Virginia University Healthcare
  • Morgantown West Virginia 26506 United States
  • Camden Clark Medical Center
  • Parkersburg West Virginia 26101 United States
  • Cancer Center of Western Wisconsin
  • New Richmond Wisconsin 54017 United States
  • Billings Clinic-Cody
  • Cody Wyoming 82414 United States
  • Welch Cancer Center
  • Sheridan Wyoming 82801 United States

View trial on ClinicalTrials.gov


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A Multicenter Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of the Combination of Rogaratinib and Copanlisib in Patients With FGFR-positive, Locally Advanced or Metastatic Solid Tumors


Condition: Advanced or Metastatic Solid Tumor

Intervention:

  • Drug: Rogaratinib (BAY1163877)
  • Drug: Copanlisib (BAY80-6946)

Purpose: The primary objective of this study is to determine the safety, tolerability, maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) and efficacy of rogaratinib in combination with copanlisib in patients with locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype. The secondary objectives of this study are to characterize the pharmacokinetics (PK) of rogaratinib and copanlisib alone and in combination, and to assess the anti-tumor efficacy of rogaratinib in combination with copanlisib locally advanced or metastatic solid tumors that are mRNA-positive for at least one FGFR1-4 subtype.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03517956

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Incidence of treatment-emergent adverse events (TEAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of drug-related TEAEs
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of treatment-emergent serious adverse events (TESAEs)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Incidence of Dose-limiting toxicities (DLTs)
  • Time Frame: Approximately 10 months
  • Safety Issue:
  • Measure: Objective response rate (ORR) at recommended dose
  • Time Frame: Up to 22 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Maximum plasma concentration of Copanlisib (Cmax)
  • Time Frame: 0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve of Copanlisib (AUC (0-48))
  • Time Frame: 0 (pre-dose), 0.5, 1 (end of infusion), 2, 4, 8, 24, 48 hours after drug administration (Days 1, 2, 3) and 0, 0.5, 1, 2, 4, 8, 24, 48 hours after drug administration (Days 15, 16, 17) in dose escalation
  • Safety Issue:
  • Measure: Area under the plasma concentration versus time curve of Rogaratinib (AUC (0-8))
  • Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Safety Issue:
  • Measure: Maximum plasma concentration of Rogaratinib (Cmax)
  • Time Frame: 0 (pre-dose), 0.5, 1, 2, 4, 6, 8 hours after drug (Day 14) and 0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 24, 48 hours after drug (Days 15 to 17) in dose escalation; 0 (pre-dose) and 1 hour after drug on Day 1 of dose expansion
  • Safety Issue:
  • Measure: Objective response rate (ORR)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Disease control rate (DCR)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Duration of response (DOR) for Partial Response and Complete Response
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Progression-free survival (PFS)
  • Time Frame: Up to 32 months
  • Safety Issue:
  • Measure: Overall survival (OS)
  • Time Frame: Up to 32 months
  • Safety Issue:

Estimated Enrollment: 65

Study Start Date: July 25, 2018

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • High FGFR mRNA expression levels (RNAscope score of ≥3; measurement is part of this protocol) in archival or fresh tumor biopsy specimen.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in contrast enhanced (unless contraindicated) CT or MRI.
  • Adequate bone marrow, liver and renal function.
  • Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula.
  • Left ventricular ejection fraction (LVEF) equal to or above the lower limit of normal (LLN) at the institution.
  • Life expectancy of at least 3 months.
  • For the dose escalation part: Patients with histologically confirmed, locally advanced or metastatic solid tumors who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anti-cancer treatment is no longer effective, excluding primary brain or spinal tumors. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.
  • For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective. Patients who have been advised with all standard treatment options and still refuse them must be documented and can be allowed to enter the trial.

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct from tumor for which the patient is enrolled in study, with exceptions
  • Ongoing or previous anti-cancer treatment within 4 weeks of study treatment start (or 6 weeks for mitomycin C, nitrosoureas and monoclonal antibodies); with exceptions.
  • Prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation (previous exposure is allowed in other circumstances). If prior toxicity to anti-FGFR-directed or anti-PI3K-directed therapies leading to treatment discontinuation is different from the known safety profile of rogaratinib or copanlisib, enrollment is allowed.
  • Symptomatic brain or meningeal metastatic tumors unless the patient is >6 months from definitive therapy, has no evidence of tumor growth on an imaging study and is clinically stable with respect to the tumor at the start of study treatment. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies).
  • History or current condition of an uncontrolled cardiovascular disease including congestive heart failure NYHA > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
  • Active hepatitis B (HBV) or C (HCV) infection.
  • Active clinically serious infections (≥ CTCAE v4.03 Grade 2).

Contact:

  • Bayer Clinical Trials Contact
  • (+)1-888-84 22937

Locations:

  • USC Norris Hospital and Clinics
  • Los Angeles California 90033 United States
  • Northwestern University
  • Chicago Illinois 60611 United States
  • University of Maryland
  • Baltimore Maryland 12101 United States
  • Dana-Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • Barbara Ann Karmanos Cancer Institute
  • Detroit Michigan 48201 United States
  • Comprehensive Cancer Centers of Nevada
  • Las Vegas Nevada 89169 United States
  • Memorial Sloan-Kettering Cancer Center
  • New York New York 10065 United States
  • Greenville Health System
  • Greenville South Carolina 29605 United States
  • Texas Oncology- Austin Midtown
  • Austin Texas 78705 United States
  • Tyler Cancer Center
  • Tyler Texas 75702 United States
  • CU Saint-Luc/UZ St-Luc
  • Bruxelles - Brussel 1200 Belgium
  • UZ Antwerpen
  • Edegem 2650 Belgium
  • CHU de Liège
  • Liege 4000 Belgium
  • Centre Oscar Lambret - Lille
  • LILLE cedex 59020 France
  • Centre Léon Bérard
  • Lyon Cedex 69008 France
  • Krankenhaus Nordwest
  • Frankfurt Hessen 60488 Germany
  • Universitätsklinikum Köln
  • Köln Nordrhein-Westfalen 50937 Germany
  • Universitätsklinikum Hamburg Eppendorf (UKE)
  • Hamburg 20246 Germany
  • Klinikum der Universität Würzburg
  • Würzburg 97080 Germany
  • Asan Medical Center
  • Seoul 05505 Korea, Republic of
  • Samsung Medical Center
  • Seoul 06351 Korea, Republic of
  • Yonsei University College of Medicine
  • Seoul 120-752 Korea, Republic of
  • National University Hospital
  • Singapore 119074 Singapore
  • National Cancer Center
  • Singapore 169610 Singapore
  • Ciutat Sanitària i Universitaria de la Vall d'Hebron
  • Barcelona 08035 Spain
  • Hospital Clínic i Provincial de Barcelona
  • Barcelona 08036 Spain
  • Hospital General Universitario Gregorio Marañón
  • Madrid 28007 Spain
  • MD Anderson International Espanya, S.A.
  • Madrid 28033 Spain
  • Hospital Clínico Universitario de Valencia
  • Valencia 46010 Spain

View trial on ClinicalTrials.gov


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