Purpose

The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination treatment of ibrutinib with everolimus, paclitaxel, docetaxel, or cetuximab in selected advanced gastrointestinal and genitourinary tumors.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • RCC (clear cell), urothelial carcinoma (transitional cell), gastric or gastro-esophageal junctional (GEJ) adenocarcinoma, or K-RAS or N-RAS wild-type EGFR expressing CRC
  • For RCC:
  • previously received at least 1 but no more than 4 lines of therapy, one therapy must have included a VEGF TKI
  • ECOG performance status of 0-1 (score of 2 may be acceptable)
  • For urothelial carcinoma:
  • previously received at least 1 but no more than 2 lines of therapy, one therapy must have included a platinum based regimen
  • ECOG performance status of 0-1
  • For gastric or GEJ adenocarcinoma:
  • previously received at least 1 but no more than 3 lines of therapy, one therapy must have included a fluoropyrimidine based regimen
  • ECOG performance status of 0-1
  • For CRC:
  • previously received at least 2 but no more than 4 lines of therapy, which must have included both an irinotecan and an oxaliplatin based regimen
  • ECOG performance status of 0-1 (score of 2 may be acceptable)
  • For all cohorts:
  • Adequate hematologic function:
  • Absolute neutrophil count (ANC) >1500 cells/mm3
  • For RCC, platelet count ≥80,000 cells/mm3
  • For urothelial carcinoma, gastric or GEJ adenocarcinoma, and CRC, platelet count ≥100,000 cells/mm3
  • For RCC, urothelial carcinoma, and gastric or GEJ adenocarcinoma, hemoglobin ≥8.0 g/dL
  • For CRC, hemoglobin ≥9.0 g/dL
  • Adequate hepatic and renal function defined as:
  • AST and/or 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)
  • Estimated Creatinine Clearance ≥30 mL/min

Exclusion Criteria

  • For RCC, prior treatment with everolimus or temsirolimus
  • For urothelial carcinoma, prior treatment with any taxane
  • For gastric or GEJ adenocarcinoma, prior treatment with any taxane
  • For CRC, prior treatment with cetuximab or panitumumab
  • 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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1b/2: Renal Cell Carcinoma
Phase 1b: Patients will receive ibrutinib at various dose levels in combination with everolimus to determine the Recommended Phase 2 Dose (RP2D) of ibrutinib. Phase 2: Patients will receive ibrutinib at the RP2D determined in Phase 1b in combination with everolimus.
  • Drug: ibrutinib
  • Drug: everolimus
Experimental
Phase 1b/2: Urothelial Carcinoma
Phase 1b: Patients will receive ibrutinib at various dose levels in combination with paclitaxel to determine the RP2D of ibrutinib. Phase 2: Subjects will receive paclitaxel at the RP2D determined in Phase 1b in combination with paclitaxel.
  • Drug: ibrutinib
  • Drug: paclitaxel
Experimental
Phase 1b/2: Gastric Adenocarcinoma
Phase 1b: Patients will receive ibrutinib at various dose levels in combination with docetaxel to determine the RP2D of ibrutinib. Phase 2: Subjects will receive docetaxel at the RP2D determined in Phase 1b in combination with docetaxel.
  • Drug: ibrutinib
  • Drug: docetaxel
Experimental
Phase 1b/2: Colorectal Adenocarcinoma
Phase 1b: Patients will receive ibrutinib at various dose levels in combination with cetuximab to determine RP2D of ibrutinib. Phase 2: Subjects will receive ibrutinib at the RP2D determined in Phase 1b in combination with cetuximab.
  • Drug: ibrutinib
  • Drug: cetuximab

Recruiting Locations

Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232
Contact:
Investigator #0024

More Details

NCT ID
NCT02599324
Status
Recruiting
Sponsor
Pharmacyclics LLC.

Study Contact

Bhagyashree Yadav
669-224-1104
byadav@pcyc.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.