A phase I-II study to evaluate the efficacy and safety of niraparib in combination with cabozantinib (XL184) in patients with advanced urothelial cancer after failure to first-line platinum-based chemotherapy.

Fundación CRIS de investigación para vencer el cáncer0 个研究点目标入组 71 人开始时间: 2019年6月11日最近更新: 2019年12月10日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 71

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

入选标准

•1. Histologically confirmed Urothelial cancer of the urinary tract or renal cell carcinoma
•2. Advanced or metastatic disease that is not amenable to curative surgery or radiation
•3. Patients must be willing to provide a tumor specimen prior to enrollment
•4. Previous therapy:
•i. Renal cell carcinoma: Prior TKI, anti PD1, anti PD-L1 and mTOR therapies is allowed
•ii. UC of the urinary tract: =2 previous chemotherapy regimens (including a platinum-based regimen). Anti PD1 and anti PD-L1 is allowed.
•5. Measurable disease will not be required
•6. The remaining inclusion/exclusion criteria will be identical to the phase II study
•7. Recovery to at least grade I from toxicities related to prior treatment unless non clinically significant or stable on supportive therapy
•1. Age =18 years
•2. ECOG PS=1
•3. Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis (patients with mixed histologies will be allowed if urothelial is the predominant component).
•4. Patients must have FFPE tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation
•5. Advanced or metastatic disease that is not amenable to curative surgery or radiation
•6. Prior treatment with one prior cytotoxic regimen of platinum-based chemotherapy.
•7. Confirmed progressive disease after treatment with platinum-based chemotherapy
•8. At least one measurable disease site that has not been previously irradiated
•9. No prior therapy with PARP or c-Met inhibitors.
•10. Adequate bone marrow, liver and renal functions as assessed by the following:
•- Hemoglobin =9 g/dL; absolute neutrophil count =1500/uL; platelets =100,000 g/uL;
•- Total bilirubin =1.5 times upper limit of normal (ULN) (=2.0 in patients with known Gilberts syndrome); ALT and AST =2.5 times ULN unless liver metastases are present, in which case they must be =5x ULN.
•- Serum creatinine =1.5x ULN or creatinine clearance =30 mL/min using Cockcroft-Gault formula
•- Urine protein/creatinine ratio (UPCR) =1 mg/mg (113.2 mg/mmol) creatinine or 24-hr urine protein of <1 g
•11. Life expectancy greater than 3 months
•12. Patients must be able to take oral medications
•13. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
•14. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
•15. Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.
•16. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
•17. Male participant agrees to use an adequate

排除标准

•1. Participant must not be simultaneously enrolled in any interventional clinical trial
•2. Major surgery, open biopsy or significant traumatic injury within 8 weeks prior to study entry and complete wound healing at the inclusion
•3. Participant must not have received investigational therapy = 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
•4. Progressed while on platinum treatment or within 2 months from completion of platinum-containing regimen
•5. Radiation therapy for bone or brain metastases within 4 weeks before first dose of study drug. Other external radiation within 4 weeks before first dose of study drug.
•6. Participant must not have a known hypersensitivity to niraparib or cabozantinib components or excipients.
•7. Participant must not have received a transfusion (platelets or red blood cells) = 4 weeks prior to initiating protocol therapy.
•8. Participant must not have received colony-stimulating factors within 4 weeks prior initiating protocol therapy.
•9. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
•10. Known history of myelodysplastic syndrome (MDS) or a pre-treatment cytogenetic testing result at risk for a diagnosis of MDS/acute myeloid leukemia (AML)
•11. Unstable systemic disease or active uncontrolled infection
•12. Any concurrent active malignancy requiring treatment
•13. Known uncontrolled symptomatic brain or leptomeningeal metastases or cranial epidural disease; subjects with brain metastases previously treated and on stable dose of corticosteroids and/or anticonvulsants for >4 weeks, or not requiring such medications, are eligible.
•14. Uncontrolled hypertension
•15. Significant cardiovascular diseases, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to inclusion, congestive heart failure > NYHA III, severe peripheral vascular disease, QT prolongation >470 msec ,clinically significant pericardial effusion
•16. Receiving concomitant medications that prolong QTc and is unable to discontinue use
•17. Concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel).
•18. Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test =1.3 x ULN within 7 days before the first dose of study treatment
•19. Significant thromboembolic or vascular disorders within 6 months prior to administration of study drugs.
•20. The subject has experienced any of the following within 3 months before the first dose of study treatment:
•- clinically significant hematemesis
•- gastrointestinal bleeding o clinically significant hemoptysis
•21. Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug
•22. Patient has not recovered to baseline

研究者

发起方

Fundación CRIS de investigación para vencer el cáncer

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