Purpose

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.

Conditions

Eligibility

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

Inclusion Criteria

  • 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 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 gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must have included a fluoropyrimidine regimen
  • For 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)

Exclusion Criteria

  • 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.

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
Renal Cell Carcinoma - Enrollment Closed
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
Urothelial Carcinoma - Enrollment Closed
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
Gastric Adenocarcinoma - Enrollment Closed
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
Colorectal Adenocarcinoma - Enrollment Closed
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
Experimental
Urothelial Carcinoma Single Agent Ibrutinib - Recruiting
Phase 1b: Patients will receive ibrutinib at various dose levels to determine the RP2D of ibrutinib Phase 2: Subjects will receive ibrutinib at the RP2D determined in Phase 1b.
  • Drug: Ibrutinib
Experimental
Urothelial Carcinoma with Pembrolizumab - Recruiting
Phase 1b: Patients will receive ibrutinib at various dose levels in combination with pembrolizumab to determine the RP2D of ibrutinib Phase 2: Subjects will receive ibrutinib at the RP2D determined in Phase 1b in combination with pembrolizumab.
  • Drug: Ibrutinib
  • Drug: Pembrolizumab

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
PCYC-1128@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.