A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors
Condition: Metastatic Renal Cell Carcinoma, Advanced Urothelial Carcinoma, Advanced Gastric Adenocarcinoma, Metastatic Colorectal Adenocarcinoma
Study Type: Interventional
Clinical Trials Identifier NCT 8-digits: NCT02599324
Sponsor: Pharmacyclics LLC.
Phase: Phase 1/Phase 2
- Age: minimum 18 Years maximum N/A
- Gender: All
- 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.
View trial on ClinicalTrials.gov