Testicular Cancer

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A Randomized Phase III Trial Comparing Conventional-Dose Chemotherapy Using Paclitaxel, Ifosfamide, and Cisplatin (TIP) With High-Dose Chemotherapy Using Mobilizing Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin and Etoposide (TI-CE) as First Salvage Treatment in Relapsed or Refractory Germ Cell Tumors


Condition: Germ Cell Tumor, Teratoma, Choriocarcinoma, Germinoma, Mixed Germ Cell Tumor, Yolk Sac Tumor, Childhood Teratoma, Malignant Germ Cell Neoplasm, Extragonadal Seminoma, Non-seminomatous Germ Cell Tumor, Seminoma

Intervention:

  • Drug: paclitaxel
  • Drug: ifosfamide
  • Drug: cisplatin
  • Drug: pegylated G-CSF
  • Drug: G-CSF
  • Drug: carboplatin
  • Drug: etoposide phosphate
  • Procedure: stem cell reinfusion

Purpose: This randomized phase III trial studies how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumors that have returned after a period of improvement or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, 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. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumors.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02375204

Sponsor: Alliance for Clinical Trials in Oncology

Primary Outcome Measures:

  • Measure: overall survival
  • Time Frame: Up to 36 months post-treatment
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: progression free survival
  • Time Frame: Up to 36 months post-treatment
  • Safety Issue:
  • Measure: proportion of patients achieving either a complete response (CR) or partial response
  • Time Frame: Up to 3 months post-registration
  • Safety Issue:
  • Measure: treatment related mortality
  • Time Frame: Up to 30 days post-treatment
  • Safety Issue:
  • Measure: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
  • Time Frame: Up to 3 months post-registration
  • Safety Issue:
  • Measure: Validation of International Prognostic Factor Study Group stratification system (eg, primary site, prior response, progression free interval)
  • Time Frame: Up to 3 years post-registration
  • Safety Issue:

Estimated Enrollment: 420

Study Start Date: March 2015

Phase: Phase 3

Eligibility:

  • Age: minimum 14 Years maximum N/A
  • Gender: Male

Eligibility Criteria:

  • (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy).
  • Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse. Patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy.
  • No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue)
  • No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process. Only one cycle is allowed.
  • No concurrent treatment with other cytotoxic drugs or targeted therapies.
  • No radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy.
  • No previous chemotherapy within 17 days prior to enrollment. A minimum of three weeks after the last day of the start of the previous chemotherapy regimen before the first day of chemotherapy on study protocol.
  • Must have adequate recovery from prior surgery (eg, healed scar, resumption of diet) 4. Age ≥ 14 years (≥ 18 years in Germany) 5. ECOG Performance Status 0 to 2 6. Male gender 7. Required Initial Laboratory Values:
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
  • Platelet Count ≥ 100,000/mm^3
  • Calculated creatinine clearance ≥ 50 mL/min
  • Bilirubin ≤ 2.0 x upper limits of normal (ULN)
  • AST/ALT ≤ 2.5 x upper limits of normal (ULN) 8. No concurrent malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or pTis) TCC of the bladder, contralateral GCT, or intratubular germ cell neoplasia. Patients with a prior malignancy, but at least 2 years since any evidence of disease are allowed. 9. Negative Serology (antibody test) for the following infectious diseases:
  • Human Immunodeficiency Virus (HIV) type 1 and 2
  • Human T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in Canada and Europe)
  • Hepatitis B surface antigen
  • Hepatitis C antibody 10. No late relapse with completely surgically resectable disease. Patients with late relapses (defined as relapse ≥ 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable are not eligible. Patients with late relapses who have unresectable disease are eligible. 11. No large (≥ 2 cm) hemorrhagic or symptomatic brain metastases until local treatment has been administered (radiation therapy or surgery). Treatment may begin ≥ 7 days after completion of local treatment. Patients with small (< 2 cm) and asymptomatic brain metastases are allowed and may be treated with radiation therapy and/or surgery concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically indicated. Radiation therapy should not be given concurrently with high-dose carboplatin or etoposide. 12. No secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression.

Contact:

  • Darren Feldman, MD
  • 646 422-4491

Locations:

  • Loma Linda University Medical Center
  • Loma Linda California 92354 United States
  • USC / Norris Comprehensive Cancer Center
  • Los Angeles California 90033 United States
  • Stanford Cancer Institute Palo Alto
  • Palo Alto California 94304 United States
  • UCSF Medical Center-Mission Bay
  • San Francisco California 94158 United States
  • University of Florida Health Science Center - Gainesville
  • Gainesville Florida 32610 United States
  • Nicklaus Children's Hospital
  • Miami Florida 33155 United States
  • Johns Hopkins All Children's Hospital
  • Saint Petersburg Florida 33701 United States
  • Emory University Hospital/Winship Cancer Institute
  • Atlanta Georgia 30322 United States
  • Northwestern University
  • Chicago Illinois 60611 United States
  • Rush University Medical Center
  • Chicago Illinois 60612 United States
  • University of Chicago Comprehensive Cancer Center
  • Chicago Illinois 60637 United States
  • Cancer Center of Kansas - Wichita
  • Wichita Kansas 67214 United States
  • Via Christi Regional Medical Center
  • Wichita Kansas 67214 United States
  • Dana-Farber Cancer Institute
  • Boston Massachusetts 02215 United States
  • University of Michigan Comprehensive Cancer Center
  • Ann Arbor Michigan 48109 United States
  • Spectrum Health at Butterworth Campus
  • Grand Rapids Michigan 49503 United States
  • Metro Health Hospital
  • Wyoming Michigan 49519 United States
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • Minneapolis Minnesota 55404 United States
  • Mayo Clinic
  • Rochester Minnesota 55905 United States
  • Washington University School of Medicine
  • Saint Louis Missouri 63110 United States
  • Nebraska Methodist Hospital
  • Omaha Nebraska 68114 United States
  • Memorial Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Memorial Sloan Kettering Monmouth
  • Middletown New Jersey 07748 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • Memorial Sloan Kettering Commack
  • Commack New York 11725 United States
  • Memorial Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Memorial Sloan Kettering Rockville Centre
  • Rockville Centre New York 11570 United States
  • UNC Lineberger Comprehensive Cancer Center
  • Chapel Hill North Carolina 27599 United States
  • Carolinas Medical Center/Levine Cancer Institute
  • Charlotte North Carolina 28203 United States
  • Cincinnati Children's Hospital Medical Center
  • Cincinnati Ohio 45229 United States
  • Ohio State University Comprehensive Cancer Center
  • Columbus Ohio 43210 United States
  • University of Oklahoma Health Sciences Center
  • Oklahoma City Oklahoma 73104 United States
  • Children's Hospital of Philadelphia
  • Philadelphia Pennsylvania 19104 United States
  • University of Pennsylvania/Abramson Cancer Center
  • Philadelphia Pennsylvania 19104 United States
  • University of Pittsburgh Cancer Institute (UPCI)
  • Pittsburgh Pennsylvania 15232 United States
  • Saint Francis Hospital
  • Greenville South Carolina 29601 United States
  • Saint Francis Cancer Center
  • Greenville South Carolina 29607 United States
  • St. Jude Children's Research Hospital
  • Memphis Tennessee 38105 United States
  • Vanderbilt University/Ingram Cancer Center
  • Nashville Tennessee 37232 United States
  • M D Anderson Cancer Center
  • Houston Texas 77030 United States
  • Froedtert and the Medical College of Wisconsin
  • Milwaukee Wisconsin 53226 United States
  • Princess Alexandra Hospital
  • Woolloongabba Queensland 4102 Australia
  • Peter MacCallum Cancer Centre
  • Melbourne Victoria 3000 Australia
  • University Hospital Saint Luc
  • Brussels 1200 Belgium
  • Institut Jules Bordet
  • Bruxelles 1000 Belgium
  • Rigshospitalet University Hospital
  • Copenhagen 2100 Denmark
  • Centre Leon Berard
  • Lyon 69373 France
  • Institut Paoli Calmettes
  • Marseille 13273 France
  • CHRU Strasbourg - Hospital Civil
  • Strasbourg 67091 France
  • Center Claudius Regaud
  • Toulouse 31052 France
  • Gustave Roussy
  • Villejuif 94805 France
  • University of Dusseldorf
  • Dusseldorf 40225 Germany
  • Saint James Hospital
  • Dublin 8 Ireland
  • Istituto Nazionale Tumori
  • Milano 20133 Italy
  • San Matteo Hospital
  • Pavia 27100 Italy
  • The Netherlands Cancer Institute
  • Amsterdam 1066 CX Netherlands
  • University Medical Center Groningen
  • Groningen 9700 GZ Netherlands
  • Radboud University Nijmegen Medical Centre
  • Nijmegen 6500 HB Netherlands
  • Hospital De La Santa Creu I Sant Pau
  • Barcelona 08025 Spain
  • Hospital General Universitario Morales Meseguer
  • Murcia 30008 Spain
  • Inselspital
  • Bern 3010 Switzerland
  • University Hospital Zurich
  • Zurich 8091 Switzerland
  • Weston Park Hospital
  • Sheffield England S10 2SJ United Kingdom
  • Southampton General Hospital
  • Southampton England SO16 6YD United Kingdom
  • Saint James's University Hospital
  • West Yorkshire England LS9 7TF United Kingdom
  • Beatson Oncology Center
  • Glasgow Scotland G12 0YN United Kingdom
  • The Royal Marsden NHS Foundation Trust - Sutton
  • Surrey SM2 5PT United Kingdom

View trial on ClinicalTrials.gov


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A Multicenter Phase II Study of Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors


Condition: Germ Cell Tumors, Testis Cancer, Testicular Cancer, Embryonal Carcinoma, Nonseminomatous Germ Cell Tumor

Intervention:

  • Drug: Brentuximab Vedotin

Purpose: This is a Phase II study to evaluate the activity of brentuximab vedotin in relapsed/refractory non-seminomatous germ cell tumors (NSGCT).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02689219

Sponsor: Costantine Albany

Primary Outcome Measures:

  • Measure: Objective response (proportion of patients who achieve either a partial or complete response)
  • Time Frame: Before cycle 3 (i.e., at +43 days)
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression free survival
  • Time Frame: From date of initiation of therapy until the time of disease progression or death (which ever comes first) up to 2 years
  • Safety Issue:
  • Measure: Toxicity
  • Time Frame: Every cycle (i.e. at +22 days, +43 days, etc.)
  • Safety Issue:

Estimated Enrollment: 58

Study Start Date: March 9, 2016

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Subject must meet all of the following applicable inclusion criteria to participate in this study: 1. Age ≥ 18 years at the time of informed consent. 2. Patients with histologically or serologically confirmed relapsed/refractory non-seminoma germ cell tumor, (i.e., embryonal carcinoma, choriocarcinoma, or yolk sac tumors) including female GCT and primary mediastinal NSGCT. 3. Patients must have progressed after prior high dose chemotherapy (HDCT) treatment, been deemed not to be a candidate for high dose chemotherapy or refused high-dose chemotherapy, and be considered incurable by other standard therapies including further chemotherapy or surgery. There is no maximum allowable number of previous therapies. "Failure" of prior therapy is defined as: 1. A >25% increase in the products of perpendicular diameters of measurable tumor masses during prior therapy which are not amenable to surgical resection. 2. The presence of new tumors which are not amenable to surgical resection. 3. An increase in AFP or beta-hCG (two separate determinations at least one week apart are required if rising tumor markers are the only evidence of failure). NOTE: Patients with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery. 4. Patients must have evidence of recurrent or metastatic carcinoma by one or more of the following: i) The appearance of metastatic disease by standard imaging techniques ii) The appearance of rising serum tumor marker, AFP or beta-hCG NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed. Patients with only evidence of disease is rising tumor marker AFP and beta-hCG will be provided alternate causes of increased serum levels of these markers are not present, such as cross reaction with luteinizing Hormone (LH) (that can be tested if needed by testosterone suppression of LH), hepatitis, use of marijuana or second primary tumor, etc. 5. Patients with primary medistinal non seminomatous germ cell tumor are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician expert opinion. 6. Patients with late relapse (>2 years) of non seminomatous germ cell tumors are eligible if they have received first line platinum based chemotherapy and their recurrence is not amenable to surgical resection based on the treating physician expert opinion. 7. Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician. 8. Patients with ECOG performance status of 0-2. 9. Adequate organ and marrow function as defined below: 1. Hemoglobin ≥ 8 g/dL 2. Absolute neutrophil count ≥ 1,000/mm3 3. Platelet count ≥ 75,000/mm3 4. Total bilirubin ≤ 1.5 × ULN except patients with documented Gilbert's syndrome (≤ 3 × ULN) 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5 × ULN 6. Calculated creatinine clearance ≥ 30 mL/min as determined by the Cockcroft-Gault equation. 10. Patients who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy for tumor cells before therapy to assess for CD30 status (unless archival tumor tissue from orchiectomy or other previous sample is not obtainable despite efforts to do so and a fresh tumor biopsy is not feasible). 11. Females of childbearing potential must not be pregnant or breast-feeding. Male and female patients of reproductive potential must agree to use two forms of highly effective contraception from the screening visit through 28 days after the last dose of study drug. Acceptable forms of effective contraception include:
  • Oral, injected or implanted hormonal methods of contraception.
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS).
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
  • Male sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
  • True abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.] Pregnancy tests for females of childbearing potential are required; must be serum at screening and the post treatment safety assessment visit. A positive urine pregnancy test must be confirmed by a serum pregnancy test and a pelvic US since some NSGCT may secrete beta-hCG and cause a false positive pregnancy. A pelvic US does not need to be repeated with each cycle unless the treating physician thinks it is necessary to do so. 12. Potential subject must have the ability to understand (as judged by the treating physician) and willingness to provide written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Written informed consent must be obtained from a potential subject prior to the conduct of any study-specific procedures.

Exclusion Criteria:

  1. Subjects meeting any of the criteria below may not participate in the study:
  2. Patients with pure seminoma.
  3. Patients with pure teratoma.
  4. Chemotherapy within 2 weeks of initiating study treatment. There is no maximum allowable number of previous therapies.
  5. Major surgery within 3 weeks of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
  6. Radiation within 2 weeks of starting study treatment.
  7. ≥ Grade 3 neuropathy at the time of enrollment.
  8. Pregnancy or breast-feeding.
  9. Previous treatment with any anti-CD30 directed therapy.

Contact:

  • Yvonne LaFary, RN
  • 317-278-5613

Locations:

  • USC/Norris Comprehensive Cancer Center
  • Los Angeles California 90033 United States
  • Indiana University Health Hospital
  • Indianapolis Indiana 46202 United States
  • Indiana University Health Melvin and Bren Simon Cancer Center
  • Indianapolis Indiana 46202 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States
  • Intermountain Precision Genomics Cancer Research Clinic
  • Murray Utah 84107 United States

View trial on ClinicalTrials.gov


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A Single-arm, Phase II Study of Durvalumab (MEDI4736) and Tremelimumab for Relapsed/Refractory Germ Cell Tumors


Condition: Germ Cell Tumor, Nonseminomatous Germ Cell Tumor, Seminoma, Germinomatous Germ Cell Tumor, Dysgerminoma, Pineal Germ Cell Tumor

Intervention:

  • Drug: Durvalumab
  • Drug: Tremelimumab

Purpose: The purpose of this study is to test the safety and effectiveness of durvalumab with tremelimumab in patients with relapsed or refractory germ cell tumors.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03158064

Sponsor: Memorial Sloan Kettering Cancer Center

Primary Outcome Measures:

  • Measure: Best confirmed overall response
  • Time Frame: 1 year
  • Safety Issue:

Estimated Enrollment: 29

Study Start Date: May 15, 2017

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Age ≥ 18 years at time of informed consent
  • Body weight > 30 kg
  • Histologically confirmed diagnosis of GCT (nonseminoma or seminoma in men; non-dysgerminomas, dysgerminomas, or germinomas in women or patients with pineal gland GCT) at MSKCC of any primary site (includes female GCT and intracranial GCT).
  • Evidence of measurable disease either by RECIST 1.1 or elevation of serum tumor markers (AFP > 15 ng/mL or HCG >2.2 mIU/ml).
  • Patients must have progressed after at least one prior systemic therapy for GCT and meet one of the following criteria: a. Patients with evidence of progressive or recurrent GCT after progression prior high dose chemotherapy (HDCT) treatment, defined as meeting at least on of the following criteria: i. Tumor biopsy of new or growing or unresectable lesions demonstrating viable GCT. In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for this study. ii. Consecutive elevated serum tumor markers (HCG or AFP) that are increasing. Increase of an elevated LDH alone does not constitute progressive disease. iii. Development of new or enlarging lesions in the the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to rise. b. Patients deemed not to be a candidate for or benefit from potentially curative HDCT or other curative treatment options defined as follows: i. Patients with inadequate renal function for HDCT. ii. Patients who have had 3 or more lines of prior chemotherapy as this patient population has historically not benefitted from HDCT. iii. Patients with late relapse (relapse > 2 years after last therapy) as this patient population has historically not benefitted from HDCT. iv. Patient with inadequate stem cell collection to move forward with HDCT. v. Patients with significant medical or psychosocial comorbidities that are felt to be a contraindication to HDCT by the treating investigator. NOTE: There is no maximum number of prior treatments allowed "Progression" after prior therapy is defined as any one of the following: NOTE: Patients with clinically growing "teratoma" (normal declining tumor markers and radiographic or clinical progression) should be considered for surgery. In patients with rising tumor markers as their only evidence of disease progression where AFP is <30 or HCG is <15, alternate causes of increased levels of these markers should be ruled out. (e.g., hypogonadism by testosterone suppression of LH, hepatitis, use of marijuana).
  • Patients with brain metastases are allowed onto the study as long as patients have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (> 1000 per mm3)
  • Platelet count ≥ 100 x 109/L (>100,000 per mm3)
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (≤ 3 x institutional ULN in patient's with Gilbert's syndrome)
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN
  • Calculated creatinine clearance >30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply.
  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women >/= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • A positive serum pregnancy test must be confirmed by a pelvic US since some NSGCT may secrete beta-hCG and cause a false positive pregnancy. A pelvic US does not need to be repeated with each cycle unless the treating physician thinks it is necessary to do so.
  • Female patients of reproductive potential, defined as not surgical sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal (see above for definition) and non-sterilized males who are sexually active with a female partner of reproductive potential must be willing to adhere to the following restrictions:
  • Females of childbearing potential who are sexually active with a non-sterilized male partner must agree to use at least 1 highly effective method of contraception from the time of screening until 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. It is strongly recommended that non-sterilized male partners of a female patient must use male condom plus spermicide throughout this period Not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice.
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Not engaging in sexual activity is an acceptable practice. Male patients should refrain from sperm donation throughout this period. It is strongly recommended that female partners (of childbearing potential) of male patients to also use a highly effective method of contraception throughout this period.
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Previous enrolment in the present study
  • Participation in another clinical study with an investigational product during the last 14 days
  • Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
  • Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab
  • Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 14 days prior to the first dose of study drug
  • Major surgery within 28 days of starting study treatment. There is no minimum time requirement for minor procedures such as biopsy or vascular access placement.
  • Radiation within 14 days of starting study treatment
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., alopecia, hearing loss, peripheral neuropathy).
  • History of pulmonary fibrosis by imaging or biopsy (including secondary to bleomycin), pneumonitis (including drug induced) requiring steroids ≥ 3 weeks, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan with associated symptoms.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis, celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc)). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with diverticulosis
  • Patients with celiac disease controlled by diet alone
  • History of primary immunodeficiency
  • History of allogeneic organ transplant
  • History of hypersensitivity to durvalumab, tremelimumab or any excipient
  • Uncontrolled intercurrent illness including, but not limited to, on-going or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known history of previous clinical diagnosis of tuberculosis
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab. Inactivated vaccines, such as the injectable influenza vaccine, are permitted.
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g. prostate cancer with Gleason score 6, and prostate-specific antigen (PSA) 10 mg/mL, etc).
  • Patients should agree to not donate blood while participating in this study or for at least 90 days following the last infusion of durvalumab or tremelimumab
  • Female patients who are pregnant or breastfeeding

Contact:

  • Samuel Funt, MD
  • 646-422-4558

Locations:

  • Memoral Sloan Kettering Basking Ridge
  • Basking Ridge New Jersey 07920 United States
  • Memorial Sloan Kettering Monmouth
  • Middletown New Jersey 07748 United States
  • Memoral Sloan Kettering Westchester
  • Harrison New York 10604 United States
  • Memorial Sloan Kettering Cancer Center
  • New York New York 10065 United States

View trial on ClinicalTrials.gov


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Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer


Condition: Adult Solid Tumor, Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Adult Central Nervous System Germ Cell Tumor, Adult Teratoma, Benign Teratoma, Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, Familial Testicular Germ Cell Tumor, HER2-negative Breast Cancer, HER2-positive Breast Cancer, Male Breast Cancer, Ovarian Immature Teratoma, Ovarian Mature Teratoma, Ovarian Monodermal and Highly Specialized Teratoma, Progesterone Receptor-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Recurrent Breast Cancer, Recurrent Colon Cancer, Recurrent Extragonadal Germ Cell Tumor, Recurrent Extragonadal Non-seminomatous Germ Cell Tumor, Recurrent Extragonadal Seminoma, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Melanoma, Recurrent Ovarian Germ Cell Tumor, Recurrent Rectal Cancer, Stage III Extragonadal Non-seminomatous Germ Cell Tumor, Stage III Extragonadal Seminoma, Stage III Malignant Testicular Germ Cell Tumor, Stage III Ovarian Germ Cell Tumor, Stage IV Breast Cancer, Stage IV Colon Cancer, Stage IV Extragonadal Non-seminomatous Germ Cell Tumor, Stage IV Extragonadal Seminoma, Stage IV Melanoma, Stage IV Ovarian Germ Cell Tumor, Stage IV Rectal Cancer, Testicular Immature Teratoma, Testicular Mature Teratoma

Intervention:

  • Drug: PD-0332991
  • Other: pharmacological study

Purpose: RATIONALE: PD 0332991 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and how well PD 0332991 works in treating patients with refractory solid tumors.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01037790

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Primary Outcome Measures:

  • Measure: Response rates
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Safety and tolerability
  • Time Frame: 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Pharmacodynamic effects on tumor and non-tumor tissue
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Relationship between selected biomarkers, pharmacokinetics, and/or efficacy and safety outcomes
  • Time Frame: 5 years
  • Safety Issue:
  • Measure: Population pharmacokinetic for PD 0332991 and correlation with efficacy outcomes
  • Time Frame: 5 years
  • Safety Issue:

Estimated Enrollment: 205

Study Start Date: October 2009

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

    Disease Characteristics:

    • All Subjects: All subjects treated under this protocol will have histologically documented cancer of one of the following types: A. Metastatic breast cancer (7 triple negative, 23 ER+ after the first 15 patients are enrolled on the non-CCND1cohort; in addition 10 HER2+ for combination trastuzumab and PD0332991 therapy) up to 55 total enrollment slots B. Metastatic colorectal cancer that harbors the Kras or BRAF mutation (15-30 enrollment slots) C. Advanced or metastatic esophageal and/or gastric cancer (15-30 enrollment slots) D. Cisplatin-refractory, unresectable germ cell tumors (15-30 enrollment slots) E. Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other functional alteration at the G1/S checkpoint. (15-30 enrollment slots)
    • Biopsy Requirements: For Subjects with accessible disease amenable to biopsy: A biopsy will be obtained pre-treatment and in during cycle 1 (while patient is receiving drug) for molecular markers of the cell cycle, and its inhibition.
    • Subjects will be > 18 years old
    • The subject has disease that is assessable by tumor marker, physical, or radiologic means.
    • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    • The subject has adequate organ function, defined as follows A. Bilirubin ≤ 1.5 x the upper limit of normal (ULN) B. Serum creatinine ≤ 1.5 x UNL or calculated creatinine clearance ≥ 60 mL/min, and C. For subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN D. For subjects with liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase ≤ 5 x ULN
    • All tumors must test positive for Rb expression except: A. ER positive metastatic breast tumors (data now shows all to be Rb positive.) B. Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other functional alteration at the G1/S checkpoint.
    • The subject has adequate marrow function, defined as follows: A. Absolute neutrophil count (ANC) >1500/mm3 B. Platelets >100,000/mm3, and C. Hemoglobin > 9 g/dL
    • The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
    • Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s).
    • Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months.
    • However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, or ovarian suppression.

    Exclusion Criteria:

    • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of PD 0332991. . Patients with HER2-overexpressing tumors may receive trastuzumab up to the date of starting therapy, and may continue to receive trastuzumab while receiving PD0332991.
    • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
    • The subject has not recovered from clinically-meaningful toxicity due to prior therapy (i.e., back to baseline or Grade ≤ 1), with the exception of neurotoxicity and alopecia.
    • The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease unless the subject has a teratoma in which case s/he may be eligible if all other

    Eligibility Criteria:

    • are met
    • The subject has uncontrolled intercurrent illness including, but not limited to: 1. ongoing or active infection 2. diabetes mellitus 3. hypertension 4. symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
    • The subject has a baseline corrected QT interval (QTc) > 470 ms.
    • The subject is pregnant or breastfeeding.
    • The subject is known to be positive for the human immunodeficiency virus (HIV). Note: baseline HIV screening is not required
    • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

    Contact:

    • Peter O Dwyer, MD
    • 855-216-0098

    Location:

    • Abramson Cancer Center of The University of Pennsylvania
    • Philadelphia Pennsylvania 19104 United States

    View trial on ClinicalTrials.gov


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