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A Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Pharmacyclics LLC.
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT02599324
First received: November 4, 2015
Last updated: August 22, 2017
Last verified: August 2017
  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.

Condition Intervention Phase
Renal Cell Carcinoma (RCC) Urothelial Carcinoma Gastric Adenocarcinoma Colorectal Adenocarcinoma (CRC) Drug: ibrutinib Drug: everolimus Drug: docetaxel Drug: paclitaxel Drug: cetuximab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors

Resource links provided by NLM:


Further study details as provided by Pharmacyclics LLC.:

Primary Outcome Measures:
  • Phase 1b: Determination of the recommended Phase 2 dose (RP2D) of ibrutinib in combination with everolimus in RCC, paclitaxel in urothelial carcinoma, docetaxel in gastric adenocarcinoma and cetuximab in CRC. [ Time Frame: Approximately 12 months after last patient enrolled ]
    Evaluated by the number of dose-limiting toxicities (DLT) graded using the NCI CTCAE v 4.03

  • Phase 2: Progression-free survival (PFS) of ibrutinib combination therapy in RCC and urothelial carcinoma [ Time Frame: Approximately 36 months after last patient enrolled. ]
    Defined by the time from the date of first dose of study drug until confirmed disease progression based on investigator assessment, per RECIST 1.1, or death from any cause, whichever comes first

  • Phase 2: ORR of ibrutinib combination therapy in gastric adenocarcinoma and CRC [ Time Frame: Approximately 36 months after last patient enrolled. ]
    Estimated using the All Treated Population as the proportion of subjects with a best response of complete response (CR) or partial response (PR) by investigator assessment


Secondary Outcome Measures:
  • Phase 2: PFS of ibrutinib combination therapy in gastric adenocarcinoma and CRC [ Time Frame: Approximately 36 months after last patient enrolled. ]
    Defined by the time from the date of first dose of study drug until confirmed disease progression based on investigator assessment, per RECIST 1.1, or death from any cause, whichever comes first

  • Phase 2: ORR of ibrutinib combination therapy in RCC and urothelial carcinoma [ Time Frame: Approximately 36 months after last patient enrolled. ]
    Estimated using the All Treated Population as the proportion of subjects with a best response of complete response (CR) or partial response (PR) by investigator assessment

  • Phase 2: DCR of ibrutinib combination therapy in each cohort [ Time Frame: Approximately 36 months after last patient enrolled. ]
    Estimated using the All Treated Population as the proportion of subjects with a best response of CR, PR or stable disease (SD) of length greater than or equal to six weeks.


Estimated Enrollment: 261
Study Start Date: November 2015
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02599324

Contacts
Contact: Bhagyashree Yadav 669-224-1104 byadav@pcyc.com
Contact: Gurvinder Singh 669-224-1168 gsingh@pcyc.com

  Show 42 Study Locations
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
Study Director: George Cole, M.D. Pharmacyclics LLC.
  More Information

Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02599324     History of Changes
Other Study ID Numbers: PCYC-1128-CA
Study First Received: November 4, 2015
Last Updated: August 22, 2017

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Adenocarcinoma
Urologic Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Everolimus
Sirolimus
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 19, 2017