A Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
Trial Status: Active
The purpose of this study is to evaluate the safety, tolerability, and efficacy of single agent ibrutinib or the combination treatments of ibrutinib with everolimus, paclitaxel, docetaxel, pembrolizumab or cetuximab in selected advanced gastrointestinal and genitourinary tumors.
- RCC (clear cell), urothelial carcinoma (UC) (transitional cell), gastric or gastro-esophageal junctional (GEJ) adenocarcinoma, or K-RAS or N-RAS wild-type EGFR expressing CRC
- For cohort 1 RCC: minimum of 1 and maximum of 4 prior regimens, one or more of which must have included a VEGF-TKI
- For UC cohort 2: minimum of 1 and maximum of 2 prior regimens, one of which must have included a platinum-based regimen
- For UC cohort 5: Minimum of 1 and maximum of 2 prior regimens, one of which must have included a checkpoint inhibitor.
- For UC cohort 6:
- Locally advanced or mUC who are not eligible for cisplatin chemo with a PDL-1 score (CPS) of ≥ 10 without prior treatment.
- Locally advanced or mUC who have progressed on platinum chemo or within 12 months of neo- or adjuvant therapy with a platinum chemotherapy. A minimum of 1 and maximum of 2 prior therapies.
- For cohort 3 gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must have included a fluoropyrimidine regimen
- For cohort 4 CRC: minimum of 2 and maximum of 4 prior regimens, which must have included both an irinotecan and an oxaliplatin based regimen unless unable to tolerate irinotecan chemotherapy Laboratory:
- Adequate hematologic function:
- Absolute neutrophil count ≥1500 cells/mm3 (1.5 x 109/L)
- Platelet count >80,000 cells/mm3 (80 x 109/L) for cohort 1 (RCC)
- Platelet counts >100,000 cells/mm3 (100 x 109/L) for all UC cohorts
- Hemoglobin ≥8.0 g/dL. for cohort 1 (RCC),all UC cohorts, and cohort 3 (GC)
- Hemoglobin ≥9.0 g/dL for cohort 4 (CRC)
- Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤5.0 x upper
- limit of normal (ULN) if liver metastases, or ≤3 x ULN without liver metastases
- Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases present
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic
- origin, such as hemolysis) with the exception of subjects in the GC cohort where
- docetaxel is administered, these subjects must have bilirubin within normal limits (WNL)
- Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault)
- Prior treatment with:
- Everolimus or temsirolimus (RCC cohort 1)
- Any taxane (UC cohort of ibrutinib + paclitaxel) (cohort 2)
- Checkpoint inhibitors (UC cohort 6)
- Any taxane (GC cohort 3)
- Cetuximab or panitumumab (CRC cohort 4)
- For all Cohorts:
- Concomitant use of warfarin or other Vitamin K antagonists
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Major surgery within 4 weeks of first dose of study drug
- Requires treatment with strong CYP3A inhibitors known bleeding disorders or hemophilia
- UC cohort 6 only:
- Subjects who have an active, known or suspected autoimmune disease.
- Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
- Non-steroid immunosuppressive medications within 14 days before the first dose of ibrutinib and pembrolizumab.
- Subjects in whom prior anti PD-1 / anti-PD-L1 therapy was intolerable and required discontinuation of treatment.
UCLA / Jonsson Comprehensive Cancer Center
Contact: Lee S. Rosen
USC / Norris Comprehensive Cancer Center
Contact: Cheryl Kefauver
UC Irvine Health / Chao Family Comprehensive Cancer Center
University of California San Diego
District of Columbia
MedStar Georgetown University Hospital
University of Iowa / Holden Comprehensive Cancer Center
University of Kansas Clinical Research Center
University of Kansas Cancer Center
University of Kansas Hospital-Westwood Cancer Center
Wayne State University / Karmanos Cancer Institute
Wake Forest University Health Sciences
OHSU Knight Cancer Institute
Contact: Matthew Hiram Taylor
University of Pennsylvania / Abramson Cancer Center
Vanderbilt University / Ingram Cancer Center
Fred Hutch / University of Washington Cancer Consortium
Trial Phase Phase I/II
Trial Type Treatment
- Primary ID PCYC-1128-CA
- Secondary IDs NCI-2016-00449
- Clinicaltrials.gov ID NCT02599324