Kidney/Renal Cancer

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A Phase II of Single Agent Cabozantinib in Patients With Locally Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma Post Immunotherapy or Who Are Unsuitable for Immunotherapy (ANZUP1802)


Condition: Renal Cell Carcinoma, Papillary Renal Cell Carcinoma Type 1, Papillary Renal Cell Carcinoma Type 2, Chromophobe Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Xp11.2 Translocation-Related Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03685448

Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed un-resectable, locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic non-clear cell renal cell histology (comprising greater than 50% of the tumour) including: 1. Papillary renal cell carcinoma (type 1) 2. Papillary renal cell carcinoma (type 2) 3. Other subtypes: including chromophobe renal cell carcinoma, sarcomatoid renal cell carcinoma, Xp11 translocation (TFE3+ IHC) carcinoma, other renal carcinoma NOS
  • Patient is either; 1. Ineligible for checkpoint inhibitor immunotherapy due to pre-existing autoimmune disorder in the opinion of the investigator, or 2. Has progressed following treatment with checkpoint inhibitor immunotherapy
  • Be greater than 18 years of age on the day of signing informed consent
  • At least 1 target lesion according to RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (refer to Appendix 1)
  • Adequate bone marrow function (performed within 14 days prior to registration and with values within the ranges specified below): 1. Haemoglobin ≥ 90g/L 2. Platelets ≥ 100x109/L 3. Neutrophil count ≥ 1.5x109/L
  • Adequate liver function (performed within 14 days prior to registration and with values within the ranges specified below): 1. Bilirubin ≤ 1.5 x upper limit of normal (ULN) except for participants with known Gilbert's syndrome who can have total bilirubin < 3.0 mg/dL 2. AST or ALT ≤ 3.0 x ULN (or ≤ 5.0x ULN in the presence of liver metastases)
  • Adequate renal function (performed within 14 days prior to registration and with values within the ranges specified below): 1. Creatinine ≤ 1.5x ULN, or Creatinine clearance (CrCl) ≥ 30mL/min (use Cockcroft-Gault Formula, refer to Appendix 2) 2. Urinalysis (dipstick) negative for protein, or for those with positive protein detected on urinalysis (≥2+), urine protein-to-creatinine ratio (UPCR) ≤ 1mg/mg (≤ 113.2mg/mmol)
  • Negative pregnancy test for female participants of childbearing potential within 72 hours prior to registration. If urine test cannot be confirmed as negative, a negative serum pregnancy test is required.
  • Female participants of childbearing potential must be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year.
  • Male participants with sexual partners of childbearing age must agree to use an adequate method of contraception, must agree to use a condom during intercourse and must agree to refrain from sperm donation starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Able to provide a formalin-fixed paraffin embedded (FFPE) tumour block, representative of the participant's primary or metastatic disease (preferred), which must be forwarded to the Centre for Biostatistics and Clinical Trials (BaCT) within 10 working days post registration (if not previously collected for the UNISoN study). Note: If FFPE tumour tissue block is not obtainable, then unstained slides are also acceptable. If archival tissue is not available, patient must be willing to provide a fresh tumour biopsy.
  • Willing and able to start treatment within 14 days of registration, and to comply with all study requirements, including the timing and/or nature of the required treatment and assessments
  • Has provided signed, written informed consent.

Exclusion Criteria:

  • Patients with urothelial or transitional cell carcinoma of the renal pelvis or ureter
  • Predominant clear cell renal cell carcinoma. A minority of clear cell histology (<50%) is acceptable, but there must be >50% non-clear cell histology predominant.
  • Untreated brain or leptomeningeal metastases or current clinical or radiological progression of known brain metastases or requirement for steroid therapy for brain metastases. Participants with treated brain metastases are eligible if metastases have been shown to be stable on repeat imaging post treatment and steroid treatment has been ceased for ≥ 3 weeks.
  • Serious Cardiovascular disorders: 1. Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. 2. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment. 3. Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before randomization.
  • Active infection requiring systemic therapy within 14 days before registration.
  • Concurrent treatment with strong CYP3A4 inducers or inhibitors (such as ketoconazole and rifampicin), P-glycoprotein substrates (such as fexofenadine, ambrisentan, dabigatran etexilate, digoxin, colchicine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol and tolvaptan), MRP2 inhibitors (such as cyclosporine, efavirenz and emtricitabine), or direct oral anticoagulants such as thrombin inhibitors or factor Xa inhibitors. Use of low molecular weight heparin (LMWH) is permitted.
  • Life expectancy of less than 3 months.
  • Prior systemic therapy, surgery or radiation therapy within 4 weeks before registation. Note: If the participant has undergone major surgery, complete wound healing must have occurred 1 month prior to registration. Patients must not have received prior targeted therapy or chemotherapy, but may have received previous checkpoint immunotherapy, for example, via the UNISoN trial (NCT03177239)
  • History of another active malignancy except for locally curable cancers that have been apparently cured, such as low-grade thyroid carcinoma, prostate cancer not requiring treatment (Gleason grade ≤ 6), basal or squamous cell skin cancer, superficial bladder cancer, melanoma in situ or carcinoma in situ of the prostate, cervix, or breast. Participants who have been treated for other malignancies and have a <5% chance of relapse according to the investigator are eligible for this study.
  • Other significant active infection, including hepatitis B, hepatitis C and HIV. Hepatitis and HIV testing is not mandatory unless clinically indicated.
  • Participants should be excluded if they have a history of allergy to study drug components or problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption
  • Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
  • Patient is pregnant or breastfeeding.

View trial on ClinicalTrials.gov


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PD-Inhibitor (Nivolumab) and Ipilimumab Followed by Nivolumab Vs. VEGF TKI Cabozantinib With Nivolumab: A Phase III Trial in Metastatic Untreated REnal Cell CancEr [PDIGREE]


Condition: Clear Cell Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Lymph Nodes, Metastatic Malignant Neoplasm in the Soft Tissues, Metastatic Malignant Neoplasm in the Viscera, Sarcomatoid Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03793166

Sponsor: National Cancer Institute (NCI)

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • STEP I REGISTRATION CRITERIA
  • Histologically documented renal cell carcinoma with clear cell component, including patients who have sarcomatoid or rhabdoid features
  • Any metastatic disease, including visceral, lymph node, other soft tissue and bone, measurable per RECIST 1.1.
  • Measurable disease as defined in the protocol.
  • Must be intermediate or poor risk patient per International Metastatic Renal Cell Carcinoma Database (IMDC) criteria (1 or more of the following): Karnofsky performance status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN], corrected calcium concentration greater than upper limit of normal [ULN], absolute neutrophil count greater than ULN, platelet count > ULN).
  • Central nervous system (CNS) disease permitted, if stable and not otherwise causing symptoms or needing active treatment.
  • Karnofsky performance status >= 70%.
  • No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab, tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting T-cell co-stimulation or checkpoint pathways. The only exception is for prior treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or post-operative trials, as long as > 1 year since completion of systemic therapy.
  • No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [> 28 days] and prior adjuvant sunitinib > 180 days since completion and prior immunotherapy as above are allowed).
  • No systemic cancer therapy less than 28 days prior to registration; no radiation therapy less than 14 days prior to registration. There must be a complete recovery and no ongoing complications from radiotherapy.
  • Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =< 14 days prior to registration is required.
  • Age >= 18 years
  • Absolute neutrophil count (ANC) >= 1,500/mm^3.
  • Platelet count >= 100,000/mm^3.
  • Hemoglobin >= 8 g/dL.
  • Calculated (Calc.) creatinine clearance >= 30 mL/min.
  • Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1.
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known or likely Gilbert's syndrome, for whom total bilirubin up to 3 mg/dL is allowed with direct bilirubin =< 20% total bilirubin)
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present.
  • STEP 2 REGISTRATION

Eligibility Criteria:

  • Successful completion of at least 1 cycle of ipilimumab/nivolumab.
  • Resolution of any treatment-related adverse events to grade 1 or less per dose modification section (this criteria does not include any adverse events [AEs] not attributable to treatment which are present due to disease), with prednisone-equivalent dosing at 10 mg daily or less. Exceptions for this criteria include patients receiving replacement hormone treatments (such as levothyroxine for treatment-related hypothyroidism or glucocorticoid replacement for adrenal insufficiency). Please contact study chair if further discussion is needed.
  • No more than 80 days from last dose of ipilimumab/nivolumab.

Exclusion Criteria:

  • Active autoimmune disease requiring ongoing therapy.
  • Ongoing acute toxicity > grade 2 from previous treatment.
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies.
  • Active hepatitis B/C, or active tuberculosis (PPD response without active TB is allowed)
  • Human immunodeficiency virus (HIV) -infected patients with detectable viral load within 6 months prior to registration. Patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible.
  • Concurrent use of immunosuppressive medication including prednisone above 10 mg daily.
  • Uncontrolled adrenal insufficiency.
  • Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP > 90 mmHg).
  • Major surgery less than 28 days prior to registration.
  • Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to registration.
  • Any arterial thrombotic events within 180 days prior to registration.
  • Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to registration.
  • Cavitating pulmonary lesions or known endotracheal or endobronchial disease manifestations.
  • Lesions encasing or invading any major blood vessels (this does not include tumor thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with tumor thrombus extending into/through renal vein are considered eligible.
  • Moderate of severe hepatic impairment (Child-Pugh B or C).
  • Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180 days prior to registration. (Any asymptomatic, treated pulmonary embolism or asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed).
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms.
  • Unstable cardiac arrhythmia within 6 months prior to registration.
  • Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of pulmonary hemorrhage =< 90 days prior to registration.
  • History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration.
  • Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome within 28 days prior to registration.
  • Untreated hypothyroidism (treated hypothyroidism on thyroid replacement therapy is allowed. Abnormal thyroid-stimulating hormone (TSH) is acceptable with normal T3/free T4 if treated on thyroid replacement therapy)
  • Evidence of pancreatitis, history of organ transplant, or history of congenital QT syndrome.
  • Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration. Allowed anticoagulants include: prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, apixaban. Allowed also in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  • Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or non-ST elevation myocardial infarction [NSTEMI]) within 6 months or active NY Heart Association class 3-4 heart failure symptoms

View trial on ClinicalTrials.gov


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Prospective Non-interventional Study of Cabozantinib as Monotherapy or in Combination With Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma Under Real-life Clinical Setting in 1st Line Treatment


Condition: Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03647878

Sponsor: Ipsen

Phase:

Eligibility:

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

Inclusion Criteria:

  • Males or females aged 18 years and older with capacity to consent.
  • Subjects receiving cabozantinib as monotherapy or in combination with nivolumab as a first line treatment for advanced or metastatic renal cell carcinoma
  • Subjects with the intention to be treated with cabozantinib tablets as monotherapy or in combination with nivolumab according to the current local Summary of Product Characteristics (SmPC); decision has to be taken before entry in the study.
  • Signed written informed consent

Exclusion Criteria:

  • Participation in an interventional study at the same time and/or within 3 months before baseline.
  • Previous participation in this study

View trial on ClinicalTrials.gov


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Preventive Effects of Low-dose Aspirin as Adjuvant Therapy After Radical Nephrectomy on Disease Recurrence/Metastasis and Survival in Patients With Locally Advanced Renal Cell Carcinoma: an Observational Prospective Cohort Study


Condition: Aspirin as Adjuvant Therapy in Patients With Surgically Treated High Risk Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03734614

Sponsor: RenJi Hospital

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients must complete radical surgery more than 4 weeks and less than 12 weeks prior to study entry
  • Patients must have histologically or cytologically confirmed renal cell carcinoma. Using 2017 (American Joint Committee on Cancer [AJCC] 8th edition) TNM Staging, patients must be one of the following:
  • pT2aG3 or G4N0M0
  • pT2bG(any)N0M0
  • pT3G(any)N0M0
  • pT4G(any)N0M0
  • pT(any)G(any)N1M0
  • Patients must have no clinical or imaging evidence of visible residual lesions or distant metastases (M0) after nephrectomy
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Patients must be able to swallow pills

Exclusion Criteria:

  • Patients with haemorrhagic diathesis (i.e. haemophilia).
  • Patients with prior malignant tumors except for kidney cancers in the past 5 years.
  • Patients with documented or suspected metastases.
  • Patients with serious, nonhealing wound, ulcer, or bone fracture.
  • Patients with a history of stroke, coronary arterial disease, angina, or vascular disease.
  • Patients who are pregnant, lactating, or not using adequate contraception.
  • Patients who have known allergy to NSAID or Aspirin.
  • Patients receiving other antiplatelet agents (i.e. clopidogrel, ticlopidine) or anticoagulants (i.e. warfarin, low molecular weight heparins).
  • Patients receiving current long term treatment (≥1 month) with Aspirin or other NSAIDs.
  • Subject unwilling or unable to comply with study requirements.

View trial on ClinicalTrials.gov


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Famitinib Malate Plus Anti-PD1 Therapy (SHR-1210) in Advanced Renal Cell Carcinoma, Urothelial Carcinoma, Advanced Cervical Cancer, Relapse Ovarian Cancer, Endometrial Cancer: Multi-institutional, Open-label, Phase 2 Trial


Condition: Renal Cell Carcinoma, Urothelial Carcinoma, Cervical Cancer, Ovarian Cancer Recurrent, Endometrial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03827837

Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Be willing and able to provide written informed consent/ for the trial. 2. Be at least 18 years of age on day of signing informed consent, male or female. 3. Patients with one of the following tumors:
  • Histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma (defined as more than 50% clear cell component) after failure of IL-2 and/or anti-VEGF TKI treatment. If patients didn't want to use anti-VEGF TKI medicine or couldn't stand anti-VEGF TKI medicine costs, they will also be considered.
  • Histologically or cytologically confirmed diagnosis of unresectable urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra (defined as more than 50% transitional cell component) after failure of no more than two prior platinum-based chemotherapeutic regimen.
  • Histologically or cytologically confirmed diagnosis of advanced squamous cell carcinoma of the cervix after failure of first-line system treatment.
  • Histologically confirmed diagnosis of recurrent or refractory epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer that are relapsed and resistant (recurred less than 6 months after chemotherapy) or refractory (progressed on chemotherapy) to prior platinum-based standard care systemic regimen.
  • Histologically confirmed diagnosis of recurrent or refractory endometrial cancer that are relapsed and resistant or refractory (progressed on chemotherapy) to prior platinum-based standard care systemic regimen. 4. At least one measurable lesion according to RECIST 1.1. 5. The patients can swallow pills. 6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. 7. Life expectancy of at least 12 weeks. 8. The results of patients' blood tests are as follows:-Neutrophils≥1.5E+9/L; - Plt≥90E+9/L; -Hb≥90g/L; -ALB≥30g/L ;-TSH≤1×ULN;-TBIL ≤ 1 ×ULN;-ALT and AST ≤ 3 ×ULN; AKP≤ 2.5×ULN; -Creatinine ≤ 1.5×ULN. 9. Male or Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.

Exclusion Criteria:

  1. Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
  2. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
  3. Known history of hypersensitivity to other antibody formulation.
  4. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 2 weeks prior to trial treatment.
  5. Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥ 90 mmHg.
  6. Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to(1)Congestive heart failure (New York heart association (NYHA) class > 2);(2)unstable or severe angina; (3)myocardial infarction within 12 months before enrollment;(4) ventricular arrhythmia which need medical intervention.(5)QTc>450ms(male)/QTc>470ms (female);
  7. Coagulation abnormalities (INR>2.0、PT>16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
  8. Bleeding history, having bleeding event(≥3 Grade according CTCAE 4.0 )within 4 weeks before screening.
  9. Tumor invasion around major vessels shown by imaging, high risk of major vascular invasion leading to massive hemorrhage judged by investigators.
  10. Previous Arterial/venous thrombosis events within 6 months.
  11. Known hereditary or acquired bleeding and thrombosis tendency.
  12. Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
  13. Prior chemotherapy, radiotherapy, surgery therapy within 4 weeks or palliative radiotherapy within 2 weeks or target therapy within 5 half-life of the drug before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade
  14. Active infection or an unexplained fever > 38.5°C within 7 days before the study drug administration, or baseline WBC>15×E+9/L .
  15. Has known history of Interstitial lung disease, or using steroids evidence of active, non-infectious pneumonitis, or would interfere with the detection and handling of suspicious drug-related pulmonary toxicity.
  16. History of immunodeficiency or human immunodeficiency virus (HIV) infection.
  17. HBV DNA>500 IU/ml,HCV RNA>1000copies/ml,HBsAg+ and anti-HCV+;
  18. Has a known additional malignancy within the last 5 years, or that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or patients with recurrent ovarian cancer has a known additional breast cancer that has been radical mastectomy and doesn't relapse within 3 years.
  19. Patients with treatment history of SHR-1210 or any other PD-L1 or PD-1 antagonists or famitinib.
  20. Patients who may receive live vaccine during the study, or previous had vaccination within 4 weeks.
  21. Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's safety and participate in the study or would interfere with the interpretation of the results or lead to the trial being terminated early.

View trial on ClinicalTrials.gov


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Phase II Study: Stereotactic Ablative Radiotherapy for Renal Tumors


Condition: Renal Tumor

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03747133

Sponsor: University Health Network, Toronto

Eligibility:

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

Inclusion Criteria:

  • Solid Kidney Mass (primary RCC or metastasis) amenable to SABR ≤6cm
  • Histological or radiological diagnosis of renal tumor
  • Inoperable: High risk for surgery or declined surgery
  • ECOG performance status of 0-3

Exclusion Criteria:

  • ≥5 active metastases
  • Sysstemic therapy (except endocrine therapy) wthin 6 days prior to SABR
  • Prior abdominal radiotherapy with fields overlap resulting in excessive doses to the involved kidney
  • Patients with end stage renal failure > 4(KDOQI guidelines)
  • Familial Syndrome: Von Hippel-Lindau disease, Polycystic Kidney Disease, Hereditary Papillary RCC or Tuber Sclerosis

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Phase II Trial of Ceralasertib (AZD6738) Alone and in Combination With Olaparib or Durvalumab in Patients With Selected Solid Tumor Malignancies


Condition: Clear Cell Renal Cell Carcinoma, Locally Advanced Pancreatic Cancer, Locally Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Metastatic Renal Cell Carcinoma, Metastatic Urothelial Carcinoma, Metastatic Pancreatic Cancer, Stage III Pancreatic Cancer, Stage III Renal Cell Cancer, Stage IV Pancreatic Cancer, Stage IV Renal Cell Cancer, Endometrial Cancer, Metastatic Castration-resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03682289

Sponsor: Rahul Aggarwal

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Patients must provide written informed consent prior to performance of study-specific procedures or assessments. 2. ARID1A Subgroup (N = 39): 1. Histologically confirmed locally advanced or metastatic solid tumor malignancy with progression on at least one prior systemic therapy, including one of the following tumor types:
  • Renal cell carcinoma with predominant clear cell histology (Cohort A)
  • Urothelial carcinoma (Cohort B)
  • All pancreatic cancers (Cohort C)
  • Other solid tumors excluding clear cell ovarian cancer and endometrial cancer (Cohort D)
  • Endometrial and ovarian cancer (Cohort E) 2. Formalin-fixed paraffin embedded tumor tissue evaluable for BAF250a expression by ARID1A immunohistochemistry. Primary or metastatic tumor tissue is permissible. Patients without evaluable archival tissue may undergo optional tumor biopsy during Screening if other

Eligibility Criteria:

  • have been met 3. Measurable disease by RECIST 1.1 3. ATM Loss Subgroup (N = 20): 1. Histologically confirmed locally advanced or metastatic solid tumor malignancy with progression on at least one prior systemic therapy, including one of the following tumor types:
  • Metastatic castration resistant prostate cancer (N = 10).
  • Patients may have evaluable or measurable disease by RECIST 1.1 criteria.
  • Prior treatment with at least one androgen signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide, darolutamide).
  • Patients will be required to maintain castrate levels of testosterone during study treatment with use of Luteinizing hormone-releasing hormone (LHRH) analog (except for patients with history of bilateral orchiectomy).
  • Progression by PCWG3 criteria at study entry
  • All other solid tumor malignancies (N = 10). Patients are required to have measurable soft tissue disease by RECIST 1.1 criteria. 2. Archival tumor tissue evaluable for ATM expression by immunohistochemistry (IHC) 3. Evidence of ATM loss by either pathogenic ATM mutation in Chemiluminescent immunoassay (CLIA)-approved assay and/or loss of ATM expression by IHC (Ventana Ab). An interim analysis will be performed after 10 patients are enrolled. If less than 50% of tumors have absence of ATM expression by IHC, subsequent enrollment of the remaining 10 patients will be required to have evidence of both ATM mutation and loss of ATM expression (< 5% of tumor cells expressing ATM) using CLIA-certified IHC test (Ventana). 4. Endometrial Cancer Cohort (N = 30): 1. Histologically confirmed endometrial cancer o A minimum of 15 patients must have the presence of pathogenic ARID1A alteration on CLIA-approved next-generation sequencing panel without evidence of microsatellite instability defined by next-generation sequencing and/or presence of intact mismatch repair proteins by immunohistochemistry. 2. Measurable disease by RECIST 1.1. 3. Availability of archival tumor tissue for retrospective testing of BAF250a expression by IHC. 4. Has received at least one prior line of systemic therapy for the treatment of locally advanced or metastatic disease, including progression on at least one prior line of therapy containing an immune checkpoint inhibitor that was administered for a minimum duration of 6 weeks
  • Must not have experienced a toxicity that led to permanent discontinuation of prior immune checkpoint inhibitor.
  • All adverse events (AE) while receiving prior immune checkpoint inhibitor must have completely resolved or resolved to baseline prior to screening for this study.
  • Must not have experienced a >= Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immune checkpoint inhibitor. NOTE: Patients with endocrine AE of <=Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
  • Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day. 5. Body weight >30 kg 6. No active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], 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 (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years may be included but only after consultation with the Principal Investigator.
  • Patients with celiac disease controlled by diet alone. 5. Evidence of clinical or radiographic progression prior to study entry (except metastatic castrate-resistant prostate cancer (mCRPC) cohort which requires progression by PCWG3 criteria). 6. Age >= 18 years at time of signing informed consent form. 7. Resolution of all prior treatment-related toxicities to grade 1 severity or lower (except alopecia). 8. Patients must be at least 3 weeks or 5 half-lives (whichever is shorter) from last standard or experimental non-cytotoxic therapy prior to first dose of protocol therapy. Patients must be > 21 days from last dose of cytotoxic chemotherapy prior to C1D1. The minimum wash-out period for immunotherapy is 42 days prior to C1D1 with the following exception for the Endometrial cohort: Note: Washout from prior immunotherapy is >=21 days to C1D1 for the Endometrial cohort. 9. Radiation therapy must be completed > 7 days prior to course 1 day 1 (C1D1) or > 28 days prior to C1D1 for patients receiving radiation to more than 30% of bone marrow. 10. Adequate organ function as defined by:
  • Hemoglobin (Hgb) >= 9.0 g/dL in the absence of transfusion within 14 days prior to screening laboratory assessment.
  • Platelets (Plt) count > 100,000 x 10^9/L.
  • Absolute neutrophil count > 1.5 x 10^9/L.
  • Estimated glomerular filtration rate (GFR) >= 45 ml/min based on Cockcroft-Gault equation or 24 hour urine collection.
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) (< 5x ULN in patients with known liver metastases).
  • Total bilirubin < 1.5 x ULN (direct bilirubin < 1.5 x ULN in patients with known Gilbert's disease or UGT1A1 homozygote). 11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 12. The effects of ceralasertib and olaparib on the developing human fetus are unknown. For this reason and because ATR and PARP inhibitors as well as other therapeutic drugs used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use 2 highly effective forms of contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 1. Male patients who are sexually active must be willing to use barrier contraception for the duration of the study and for 1 week after the last study drug administration, with all sexual partners. Male patients must use a condom during treatment and for 6 months after the last dose of study drug(s) when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception for 6 months after the last dose of study drug(s) if they are of childbearing potential. True abstinence for either sex is an acceptable form of contraception and must be documented as such. 2. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to C1D1 treatment. Evidence of postmenopausal status or non-child bearing status must be documented. Postmenopausal is defined as:
  • Aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
  • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation, radiation-induced oophorectomy with last menses > 1 year ago, chemotherapy-induced menopause with > 1 year interval since last menses
  • Amenorrhoeic for 12 months and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the postmenopausal range for the institution for women under 50. 13. Ability to understand a written informed consent document, and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.

Exclusion Criteria:

  • 1. History of secondary malignancy requiring treatment within 1 year prior to screening, with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, low/intermediate risk localized prostate cancer (=< Gleason 7, =< T2N0M0, and prostate-specific antigen (PSA) =< 20 ng/mL at diagnosis) (not applicable for prostate cancer cohort), ductal carcinoma in situ, Stage I uterine cancer, and non-muscle invasive urothelial carcinoma 2. Patients receiving, or having received within 14 days of C1D1, corticosteroids at a dose > 10 mg/day of prednisone (or equivalent). 3. Patients with myelodysplastic syndrome or features suggestive of myelodysplastic syndrome. 4. Prior treatment with ATR inhibitor 5. Major surgical procedures < 28 days prior to C1D1. Patients must have recovered to grade =< 1 for any adverse events related to the surgical procedure. 6. Untreated central nervous system (CNS) metastases. Patients with previously treated central nervous system (CNS) metastases are eligible if:
  • No requirement for corticosteroids at study entry
  • Radiographically and clinically stable for at least 4 weeks prior to study entry
  • No evidence of intra-tumoral hemorrhage
  • No evidence of current or prior leptomeningeal disease. 7. Clinically significant gastrointestinal abnormalities that may increase the risk of decreased absorption of medications, including:
  • Inability to swallow oral medications
  • Active peptic ulcer disease
  • Known intra-luminal metastatic lesions
  • History of abdominal fistula or bowel perforation
  • History of bowel obstruction within 6 months prior to study entry
  • Known malabsorption syndrome
  • Significant resection of the small bowel. 8. Fridericia's QT correction formula (QTcF) > 470 ms (females) or > 450 ms (males) on screening electrocardiography (ECG), or immediate family history of congenital long QT syndrome or sudden cardiac death at age less than 40. 9. History of any one or more of the following cardiovascular conditions within the past 6 months:
  • Myocardial infarction
  • Unstable angina
  • Transient ischemic attack or cerebrovascular accident
  • Uncontrolled arrhythmia. Rate controlled atrial fibrillation/flutter is not an exclusion for the study.
  • Class III or IV congestive heart failure or documented left ventricle (LV) ejection fraction of < 50% (screening not required). 10. Uncontrolled hypertension as defined by systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg. Adjustment of anti-hypertensive regimen and re-screening is permitted. 11. Relative hypotension with resting blood pressure of less than 90 mm Hg systolic and less than 60 mm Hg diastolic or symptomatic orthostatic hypotension. 12. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety or adherence to study procedures including uncontrolled infection requiring parenteral antibiotics. 13. Concomitant use of strong cytochrome P450, family 3, subfamily A (CYP3A4) inhibitors, strong CYP3A4 inducers, CYP3A4 substrates with narrow therapeutic index, or CYP2B6 substrates with narrow therapeutic index within 21 days or 5 half-lives, whichever is shorter, prior to C1D1 of study treatment
  • The use of herbal supplements or 'folk remedies' (and medications and foods that significantly modulate CYP3A activity) should be discouraged. If deemed necessary, such products may be administered with caution and the reason for use documented in the case report form (CRF). 14. A known hypersensitivity to olaparib, ceralasertib, durvalumab (as applicable to the study drugs the patient is receiving), or any excipient of the product or any contraindication to the combination anti-cancer agent as per local prescribing information. 15. A known chronic active hepatitis B or C (defined by positive viral load; screening not required). 16. Immunocompromised patients, including those serologically positive for human immunodeficiency virus (HIV), those receiving chronic immunosuppression, or those with prior allogeneic or cord blood transplantation.

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Kidney Cancer DNA Registry


Condition: Renal Cancer

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02087852

Sponsor: Memorial Sloan Kettering Cancer Center

Phase:

Eligibility:

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

Inclusion Criteria:

  • Kidney Cancer Case Cohort:
  • Must be ≥ 18 years of age AND
  • Must be an English-speaker AND
  • Must have a diagnosis or suspicion of kidney cancer Family Member Cohort:
  • Must be ≥ 18 years of age AND
  • Must be an English-speaker AND
  • Must be a blood relative of the proband. Family members of probands including mother, father, sisters, brothers, half-sisters, half-brothers, daughters, sons, grandmothers, grandfathers, as well as aunts and uncles are eligible. These individuals need not have kidney cancer, as they will be used for segregation analysis of suspected variants found in the proband; requesting DNA from relatives is required. Control Cohort:
  • Must be ≥ 18 years of age AND
  • Must be an English-speaker AND
  • Must not have a personal history of cancer, with the exception of nonmelanoma skin cancer, AND
  • Must not be a blood relative of any cases or controls enrolled in this study

Exclusion Criteria:

  • Patients who, in the opinion of the primary MSKCC clinician or the investigator, have a condition that precludes their ability to provide an informed consent

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An International Investigator-led Phase III Multi Arm Multi Stage Multi-centre Randomised Controlled Platform Trial of Adjuvant Therapy in Patients With Resected Primary Renal Cell Carcinoma (RCC) at High or Intermediate Risk of Relapse


Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03288532

Sponsor: University College, London

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  1. Histologically proven RCC (all cell types of RCC are eligible, except for pure oncocytoma, collecting duct, medullary and transitional cell cancer [TCC]); no evidence of residual macroscopic disease on post-operative CT scan after resection of RCC. Patients with treated bilateral synchronous RCCs are eligible.
  2. At the start of recruitment patients with Leibovich score 3-11 will be eligible for randomisation. MRC CTU at UCL will monitor accrual and stop recruiting intermediate risk patients (Leibovich Score 3-5) after three years or when intermediate risk patients contribute 25% of the total accrual target, whichever is earlier. Recruitment of patients with Leibovich Score 6 11 will continue until the accrual target is reached.
  3. Patients should have had surgery at least 28 days but no more than 91 days prior to their randomisation date.
  4. Post-operative scans should be performed within 28 days prior to randomisation.
  5. Patients with microscopically positive resection margins after radical nephrectomy at the nephrectomy bed, renal vein or inferior vena cava are eligible provided the post-operative CT scan shows no evidence of residual macroscopic disease.
  6. WHO Performance Status 0 or
  7. Patient has archival FFPE pathology tissue available, and agrees to provide at least one sample (FFPE tumour block from nephrectomy, or a minimum of 10 unstained slides), as well as a baseline EDTA blood sample for future translational research).
  8. Adequate normal organ and marrow function
  9. Haemoglobin ≥9.0g/dL (transfusions will be allowed within 2 weeks prior to randomisation in order to achieve the entry criteria).
  10. Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500 per mm3).
  11. Platelet count ≥100 x 109 (≥100,000 per mm3).
  12. Bilirubin ≤1.5 x ULN (This will not apply to subjects with confirmed Gilbert's syndrome (i.e., persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician).
  13. AST/ALT ≤2.5 x ULN.
  14. Calculated Creatinine Clearance level >40mL/min by Cockcroft Gault formula (using actual body weight).
  15. 12-lead ECG on which QTcF must be <450 ms. In case of clinically significant ECG abnormalities, including a QTcF value ≥450 ms, two additional 12-lead ECGs should be obtained over a brief period (e.g., 30 minutes) to confirm the finding. Patients are only eligible if a QTcF of <450ms is confirmed
  16. Subjects must be ≥18 years of age.
  17. Written informed consent obtained from the patient.
  18. Both men and women enrolled in this trial must be in agreement with trial policy on contraception during the treatment phase of the study and 6 months afterwards. Egg donation, sperm donation and breastfeeding must be avoided.
  19. Evidence of post-menopausal status or negative serum HCG pregnancy test for female pre menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age specific requirements apply:
  20. Women <50 years of age will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilisation (bilateral oophorectomy or hysterectomy).
  21. Women ≥50 years of age will be considered post-menopausal if they have been amenorrhoeic 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 sterilisation (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

Exclusion Criteria:

  1. Previous diagnosis of RCC.
  2. Metastatic or macroscopic residual disease.
  3. Patients with positive resection margins after partial nephrectomy.
  4. Patients with a single pulmonary nodule ≥5mm diameter are not eligible unless the nodule has had a definite benign diagnosis. Patients with multiple small, less than 5 mm nodules may be eligible if nodules have been shown to be radiologically stable for at least 8 weeks.
  5. Prior anticancer treatment (other than nephrectomy) for RCC.
  6. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  7. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  8. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
  9. History of another primary malignancy except for:
  10. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence.
  11. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  12. Adequately treated carcinoma in situ without evidence of disease.
  13. History of leptomeningeal carcinomatosis.
  14. Concurrent enrolment in another clinical study, unless it is an observational (non interventional) clinical study or during the follow up period of an interventional study.
  15. Major surgical procedure (as defined by the Investigator) within 28 days prior to the start of treatment. Local surgery of isolated lesions for palliative intent is acceptable.
  16. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
  17. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], 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:
  18. Patients with vitiligo or alopecia
  19. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  20. Any chronic skin condition that does not require systemic therapy
  21. Patients without active disease in the last 5 years may be included but only after consultation with the RAMPART Trial Management Team
  22. Patients with coeliac disease controlled by diet alone
  23. A history of immunodeficiency syndrome. Please consult the MRC CTU at UCL on an individual basis if there is any uncertainty.
  24. History of allogeneic organ transplant.
  25. Uncontrolled intercurrent illness including, but not limited to:
  26. Ongoing or active infection of any kind (patients who are exhibiting symptoms consistent with COVID-19, or who have tested positive, should not be randomised into the study until they are asymptomatic and at least 14 days after a positive test)
  27. Symptomatic congestive heart failure
  28. Uncontrolled hypertension
  29. Unstable angina pectoris
  30. Uncontrolled cardiac arrhythmia
  31. Active peptic ulcer disease or gastritis
  32. Active bleeding diatheses
  33. Psychiatric illness or social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
  34. Active infection including
  35. Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice)
  36. Hepatitis B (known positive HBV surface antigen (HBsAg) result). 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.
  37. Hepatitis C
  38. Human immunodeficiency virus (positive HIV 1/2 antibodies). Note: Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  39. Receipt of live attenuated vaccine within 30 days prior to the start of treatment. Note: Patients, if enrolled, should not receive live vaccine while receiving investigational medicinal product and up to 30 days after the last dose of investigational medicinal product.
  40. Pregnant or breastfeeding patients.
  41. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
  42. Known allergy or hypersensitivity to durvalumab or tremelimumab, or any of their excipients.
  43. Previous investigational medicinal product assignment in the present study.
  44. Clinically significant pneumonitis or fibrosis.

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Phase Ib Trial Of Pembrolizumab And Nintedanib


Condition: Patients With Any Advanced Solid Tumors

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02856425

Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • 1. Age ≥ 18 2. Patients with advanced/metastatic cancer who have progressed after at least one line of standard therapy or are intolerant to standard therapy. Patients must fit into one of the following groups: Colorectal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC) Gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC Patients with advanced or metastatic Urothelial cancer (UC) Patients with advanced Renal Cell cancer (RCC) Patients with advanced Mesothelioma (MPM) Patients with advanced squamous cell carcinoma in Cervical Cancer (CC) Patients with advanced Hepatocellular (HCC) Patients with advanced Thymic Carcinoma (TC) Patients with advanced cancers and high tumor mutational burden (TMB-High) on their circulating tumor DNA (ctDNA) as defined by more than twenty mutations per megabase (≥20Mut/Mb) on FoundationOne Liquid CDx assay. Patients should be without known therapeutic options to provide clinical benefit. 3. ECOG performance status of score 0 or 1 4. Adequate organ function as defined by the following criteria :
  • Proteinuria ≤ Grade 2 NCI CTCAE v4.03
  • Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min
  • Total bilirubin within normal range (≤ 1.5 x ULN if HCC)
  • AST and ALT ≤ 1.5 x upper limit of normal (ULN); if liver metastases AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN if HCC)
  • Coagulation parameter : International normalized ratio (INR) < 2, prothrombin time (PT) and partial thromboplastin time (PTT) < 50% of deviation of ULN
  • Absolute Neutrophils count (ANC) ≥ 1000 cells/mm^3
  • Platelets ≥100 000 cells/mm^3
  • Hemoglobin ≥ 9.0 g/dL 5. At least one measurable lesion according to RECIST v1.1 (Appendix 4) criteria and modified RECIST for mesothelioma only (Appendix 6) or any other baseline prerequisite for the assessment of the principal judgment criteria. 6. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Both sexually active females and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 4 months after last study drug administration. 7. Signed and dated written informed consent prior to admission to the study 8. Patient affiliated to a social security regimen or beneficiary of the same

Exclusion Criteria:

  1. Prior treatment with nintedanib
  2. Known hypersensitivity to trial drugs or their excipients, peanut or soya or to contrast media
  3. Prior treatment with pembrolizumab or any other anti PD1 or anti-PDL1 agents
  4. Concurrent steroid medication (except topical or aerosol steroids). Any steroid medication should have been stopped for more than 7 days prior beginning of therapy.
  5. History of autoimmune/immune mediated inflammatory disease, including but not limited to colitis, pneumonitis, hepatitis, hypophysitis, nephritis, hyperthyroidism, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, vasculitis, or glomerulonephritis (see Appendix 3). Patients with a history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. Patients with a history of vitiligo, pelade, cutaneous psoriasis and grade 1-2 Sjogren syndrome are eligible.
  6. Chemo-, hormono-, radio- (except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with the trial drugs.
  7. Administration of a live, attenuated vaccine within 4 weeks before registration
  8. Treatment with systemic immunosuppressive medications (including but not limited to steroids azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to registration
  9. Radiotherapy to the target lesion (unless a progression after radiotherapy has been documented)
  10. Persistence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy
  11. Active brain metastases or leptomeningeal disease. Clinically asymptomatic brain metastases and clinically asymptomatic leptomeningeal disease are allowed (treatment with steroids prior initiation of the trial is not allowed). Patients with Diffuse Intrinsic Pontine Gliomas, even asymptomatic, are not allowed.
  12. Radiographic evidence of cavitary tumors with local invasion of major blood vessels and/or at risk for perforation
  13. History of clinically significant hemoptysis within the past 3 months (more than one teaspoon of fresh blood per day)
  14. Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial
  15. Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid < 325mg per day)
  16. Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
  17. History of clinically significant hemorrhagic or thromboembolic event in the past 6 months
  18. Known inherited (genetic) predisposition to bleeding or thrombosis (such deficit in protein C/S) or acquired predisposition to thrombosis (such as anti-phospholipid syndromes)
  19. History of significant cardiovascular diseases ( i.e. supraventricular tachycardia, uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
  20. Ongoing uncontrolled auto-immune thyroiditis. Ancient thyroiditis currently stable with substitutive therapy should not be excluded from the trial.
  21. Other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix. A history of more than 3 years of local prostate cancer treated by surgery and without PSA elevation since surgery, or local breast carcinoma treated by surgery without relapse are eligible.
  22. Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy
  23. Known to be human immunodeficiency virus (HIV) positive;
  24. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
  25. Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
  26. Pregnancy or breast feeding,
  27. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
  28. Active alcohol or drug abuse
  29. Intake of Ganoderma Lucidum mushroom and/or herbal remedies and/or traditional medicines within the past 4 weeks prior to start of study treatment or concomitantly with the trial

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Combined Haploidentical Reduced Intensity Bone Marrow and Kidney Transplantation for Patients With Chronic Kidney Disease and Advanced Hematological Disorders


Condition: Chronic Kidney Disease, Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Myelogenous Leukemia (CML), Chronic Lymphocytic Leukemia (CLL), Non-Hodgkin's Lymphoma (NHL), Hodgkin Disease, Multiple Myeloma, Myelodysplastic Syndrome (MDS), Aplastic Anemia, AL Amyloidosis, Diamond Blackfan Anemia, Myelofibrosis, Myeloproliferative Disease, Sickle Cell Anemia, Autoimmune Diseases, Thalassemia

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01758042

Sponsor: Massachusetts General Hospital

Eligibility:

  • Age: minimum 18 Years maximum 70 Years
  • Gender: All

Inclusion Criteria:

  • Patients ages 18-70
  • Underlying hematological disorder which is potentially curable with allogeneic bone marrow transplantation. This includes, but is not limited to: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS), AL amyloidosis, diamond blackfan anemia, myelofibrosis or other myeloproliferative disease, sickle cell anemia, and thalassemia.
  • Existence of haploidentical first degree relative who passes standard donor evaluations for bone marrow and kidney donation
  • LVEF > 40% as measured by echocardiography or MUGA
  • FEV1, FVC, and DLCO > 50% of predicted as measured by standard PFTs
  • Total bilirubin < 2.0 (unless diagnosis of Gilbert's or hemolysis is made) and AST, ALT, alkaline phosphatase all < 5x institutions upper limit of normal
  • ABO compatibility in the host vs. graft direction
  • Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 1 year following the transplant.
  • Participants should be on dialysis or have an estimated or measured CrCl < 35 ml/min
  • Life expectancy greater than six months.
  • Recipient ability to understand and provide informed consent

Exclusion Criteria:

  • Active serious infection
  • Participation in other investigational drug use at the time of enrollment
  • Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to rabbit serum in ATG)
  • Serologic positivity for HIV, HCV, or HbsAg positivity
  • ABO blood group incompatibility in the host-vs-graft direction
  • Active serious infection

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177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.


Condition: Thyroid Cancer, Medullary, Neuroendocrine Tumor of the Lung Grade 1 and 2, Neuroendocrine Tumor of the Thymus Grade 1 and 2, Neuroendocrine Tumor GEP Grade 1-3

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02088645

Sponsor: University Hospital, Basel, Switzerland

Phase: Phase 1

Eligibility:

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

Inclusion Criteria:

  • Phase 0 study
  • Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy or
  • Patients with well differentiated GEP-NET (grade 1-3) with a Ki67 index of up to 55% or NET of the lung or thymus (grade 1 and 2) with low or missing expression of SST2-receptor and progressive disease within the last 6 months according to RECIST 1.1
  • Age > 18 years
  • Informed consent Phase I study
  • Diagnostic, contrast medium enhanced CT scan neck/thorax/abdomen, not older than 4 weeks
  • Advanced MTC with elevated levels of calcitonin (> 100 pg/ml) and/or calcitonin-doubling time < 24 months before or after total thyroidectomy- Age > 18 Years
  • Informed consent
  • Curative surgical therapy not possible

Exclusion Criteria:

  • Phase 0 study
  • Medication with Vandetanib 3 weeks before the study and during the study
  • Renal failure (calculated glomerular filtration rate (GFR) < 60 ml/min per 1.73 m2 body surface).
  • Bone marrow failure (thrombocytes < 70 000/μl, leucocytes < 2 500/μl, hemoglobin < 8 g/dl).
  • Pregnancy and breast feeding
  • Knows allergic reaction on Physiogel or other gelatine products
  • Known, serious side reaction in the case of a former application of pentagastrin
  • Active, second malignancy oder remission after second malignancy < 5 years Phase I study
  • Medication with Vandetanib 3 weeks before the study and during the study
  • Renal failure (calculated GFR < 50 ml/min per 1.73 m2 body surface).
  • Bone marrow failure (thrombocytes < 100 000/μl, leucocytes < 3 000/μl, hemoglobin < 10 g/dl).
  • Pregnancy and breast feeding
  • Known, serious side reaction in the case of a former application of pentagastrin
  • Active, second malignancy oder remission after second malignancy < 5 years

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An Open-label Phase II Study of Lutetium-177 [DOTA0, Tyr3] Octreotate (Lu-DOTA-TATE) Treatment in Patients With Somatostatin Receptor Positive Tumours


Condition: Carcinoma, Neuroendocrine

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01876771

Sponsor: AHS Cancer Control Alberta

Phase: Phase 2

Eligibility:

  • Age: minimum 14 Years maximum 90 Years
  • Gender: All

Inclusion Criteria:

  • 1. Male or female ≥ 14
  • 90 years of age. 2. Presence of somatostatin receptor positive tumour(s) on radionuclide imaging, with uptake greater than liver background as assessed by planar Octreoscan® images or Ga-68 labelled somatostatin analogue (68Ga-DOTATATE or 68Ga-HA-DOTATATE) PET imaging, with at least 1 tumour site reliably evaluable by CT or magnetic resonance imaging (MRI) of at least 1.0 cm (smallest dimension) or >1.5 cm lymph node disease (smallest dimension) (the target lesion) within 26 weeks of enrolment. 3. Histologically confirmed diagnosis of neuroendocrine tumor. 4. Progressive disease documented by anatomic imaging and/or presence of new lesions on somatostatin receptor imaging assessed by comparable studies. In the opinion of the investigator, patients with no progression on imaging may still be considered eligible in presence of carcinoid symptoms refractory to treatment with somatostatin receptor analogues. 5. 18F-FDG PET/CT whole-body imaging within 26 weeks of enrolment. 6. Life expectancy greater than 12 weeks from enrollment. 7. Serum creatinine ≤ 150 µmol/L, and a calculated (Cockcroft-Gault) or estimated GFR of ≥ 50 mL/min measured within 2 weeks of enrollment. 8. Haemoglobin concentration ≥ 90 g/L; white blood cell (WBC) count ≥ 2 x 10^9/L; platelets ≥ 100 x 10^9/L measured within 2 weeks of enrolment. 9. Liver function tests (total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase) ≤ 3X the limit of normal measured within 2 weeks of enrolment. Serum albumin ≥ 23 g/L within 2 weeks of enrolment. 10. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within 2 weeks of enrolment. 11. Provide written informed consent prior to enrolment. Group B (Maintenance Therapy) Inclusion Criteria: 1. Male or female ≥ 14
  • 90 years of age. 2. Have previously received Lu-DOTA-TATE treatment under the SAP. 3. Life expectancy greater than 12 weeks from enrolment. 4. Serum creatinine ≤ 150 μmol/L, and a calculated (Cockcroft-Gault) or estimated glomerular filtration rate (GFR) of ≥ 50 mL/min measured within 2 weeks of enrolment. 5. Haemoglobin concentration ≥ 90 g/L; white blood cell (WBC) count ≥ 2 x 10^9/L; platelets ≥ 100 x 10^9/L measured within 2 weeks of enrolment. 6. Liver function tests (total bilirubin, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase) ≤ 3X the limit of normal measured within 2 weeks of enrolment. Serum albumin ≥ 23 g/L within 2 weeks of enrolment. 7. Eastern Cooperative Oncology Group (ECOG) Performance Scale Score ≤ 2 measured within 2 weeks of enrolment. 8. Provide written informed consent prior to enrolment. Group A (Primary Therapy) Exclusion Criteria: 1. Have previously received Lu-DOTA-TATE therapy. 2. Potential for surgery with curative intent. Local surgery for symptomatic relief permitted as long as target lesion unaffected. 3. Surgery within 12 weeks of enrolment. Surgery for removal of superficial skin lesions, laser eye surgery, or cataract surgery is permitted. 4. Liver embolization [transcatheter arterial embolization (TAE), TACE, or TARE] within 4 weeks of enrolment. 5. Radioisotope therapy within 12 weeks of enrolment. 6. Systemic therapy: mTOR inhibitors and tyrosine kinase inhibitors within 6 weeks of enrolment; chemotherapy and interferon within 8 weeks of enrolment. 7. Change in long acting somatostatin analogues, dosage, or dosage frequency within 12 weeks of enrolment. 8. Localized external beam irradiation with target lesion(s) in the radiation field. Other localized external beam therapy is permitted. 9. Known brain metastases unless these metastases have been treated and stabilized (confirmed by CT) for ≥ 4 months prior to enrolment 10. Uncontrolled diabetes mellitus defined as random glucose ≥ 2X the upper limit of normal (or HbA1c > 10%, if results available) within 12 weeks of enrolment. 11. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary incontinence, co-existing malignancies). 12. Pregnancy. 13. Breast feeding. 14. Prior radiation therapy to more than 25% of the bone marrow. 15. If, in the opinion of the investigator, other treatments are considered more appropriate than the investigational therapy, based on patient and disease characteristics. Group B (Maintenance Therapy)

Exclusion Criteria:

  1. Have previously received Lu-DOTA-TATE therapy.
  2. Potential for surgery with curative intent. Local surgery for symptomatic relief permitted as long as target lesion unaffected.
  3. Surgery within 12 weeks of enrolment. Surgery for removal of superficial skin lesions, laser eye surgery, or cataract surgery is permitted.
  4. Liver embolization [transcatheter arterial embolization (TAE), TACE, or TARE] within 4 weeks of enrolment.
  5. Radioisotope therapy within 12 weeks of enrolment.
  6. Systemic therapy: mTOR inhibitors and tyrosine kinase inhibitors within 6 weeks of enrolment; chemotherapy and interferon within 8 weeks of enrolment.
  7. Change in long acting somatostatin analogues, dosage, or dosage frequency within 12 weeks of enrolment.
  8. Localized external beam irradiation with target lesion(s) in the radiation field. Other localized external beam therapy is permitted.
  9. Known brain metastases unless these metastases have been treated and stabilized (confirmed by CT) for ≥ 4 months prior to enrolment
  10. Uncontrolled diabetes mellitus defined as random glucose ≥ 2X the upper limit of normal (or HbA1c > 10%, if results available) within 12 weeks of enrolment.
  11. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary incontinence, co-existing malignancies).
  12. Pregnancy.
  13. Breast feeding.
  14. Prior radiation therapy to more than 25% of the bone marrow.
  15. If, in the opinion of the investigator, other treatments are considered more appropriate than the investigational therapy, based on patient and disease characteristics. Group B (Maintenance Therapy) Exclusion Criteria:
  16. Another significant medical, psychiatric or surgical condition uncontrolled by treatment, which may interfere with completion or conduct of the study (such as urinary incontinence or co-existing malignancies).
  17. Pregnancy.
  18. Breast feeding.

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