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

NCT02599324

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Clear Cell Renal Cell Carcinoma
  • Colorectal Carcinoma
  • Gastric Adenocarcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
  • Official Title: A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors

Clinical Trial IDs

  • ORG STUDY ID: PCYC-1128-CA
  • NCT ID: NCT02599324

Conditions

  • Metastatic Renal Cell Carcinoma
  • Advanced Urothelial Carcinoma
  • Advanced Gastric Adenocarcinoma
  • Metastatic Colorectal Adenocarcinoma

Interventions

DrugSynonymsArms
IbrutinibRenal Cell Carcinoma - Enrollment Closed
EverolimusRenal Cell Carcinoma - Enrollment Closed
DocetaxelGastric Adenocarcinoma - Enrollment Closed
PaclitaxelUrothelial Carcinoma - Enrollment Closed
CetuximabColorectal Adenocarcinoma - Enrollment Closed
PembrolizumabUrothelial Carcinoma with Pembrolizumab - Recruiting

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.

Trial Arms

NameTypeDescriptionInterventions
Renal Cell Carcinoma - Enrollment ClosedExperimentalPhase 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.
  • Ibrutinib
  • Everolimus
Urothelial Carcinoma - Enrollment ClosedExperimentalPhase 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.
  • Ibrutinib
  • Paclitaxel
Gastric Adenocarcinoma - Enrollment ClosedExperimentalPhase 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.
  • Ibrutinib
  • Docetaxel
Colorectal Adenocarcinoma - Enrollment ClosedExperimentalPhase 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.
  • Ibrutinib
  • Cetuximab
Urothelial Carcinoma Single Agent Ibrutinib - RecruitingExperimentalPhase 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.
  • Ibrutinib
Urothelial Carcinoma with Pembrolizumab - RecruitingExperimentalPhase 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.
  • Ibrutinib
  • Pembrolizumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: To determine the recommended Phase 2 dose (RP2D) of ibrutinib in combination with everolimus in RCC, paclitaxel in UC cohort 2, docetaxel in GC, cetuximab in CRC, and pembrolizumab in UC cohort 6
Time Frame:Approximately 6 months after evaluation
Safety Issue:
Description:Evaluated by the number of dose-limiting toxicities (DLT) graded using the NCI CTCAE v 4.03

Secondary Outcome Measures

Measure:Phase 2: To assess the PFS of ibrutinib combination therapy in GC, CRC, and UC cohort 6, and ibrutinib as a single agent in UC cohort 5.
Time Frame:Approximately 12 months
Safety Issue:
Description: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.
Measure:Phase 2: To assess the ORR of ibrutinib combination therapy in RCC and UC cohort 2.
Time Frame:Approximately 12 months
Safety Issue:
Description:Defined by the proportion of subjects with a best response of complete response (CR) or partial response (PR) by investigator assessment, per RECIST 1.1.
Measure:Phase 2: To assess the DOR in each cohort
Time Frame:Approximately 12 months
Safety Issue:
Description:Defined for responders as duration of time from initial response (CR or PR by investigator assessment) to first documentation of disease progression or death from any cause, whichever occurs first.
Measure:Phase 2: To assess the DCR in each cohort
Time Frame:Approximately 12 months
Safety Issue:
Description:Defined by the proportion of subjects with a best response of complete response (CR), partial response (PR), stable disease (greater than or equal to 6 weeks) by investigator assessment, per RECIST 1.1.
Measure:Phase 2: To assess the median OS of ibrutinib combination or single-agent therapy in each cohort
Time Frame:Approximately 24 months
Safety Issue:
Description:Defined as the time from first dose of study drug to death due to any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pharmacyclics LLC.

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