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

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ClinicalTrials.gov Identifier: NCT02599324
Recruitment Status : Recruiting
First Posted : November 6, 2015
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Advanced Urothelial Carcinoma Advanced Gastric Adenocarcinoma Metastatic Colorectal Adenocarcinoma Drug: Ibrutinib Drug: Everolimus Drug: Docetaxel Drug: Paclitaxel Drug: Cetuximab Drug: Pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 348 participants
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
Actual Study Start Date : November 2015
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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 ]
    Evaluated by the number of dose-limiting toxicities (DLT) graded using the NCI CTCAE v 4.03

  2. Phase 1b: To confirm the RP2D of single-agent ibrutinib in UC cohort 5 [ Time Frame: Approximately 6 months after evaluation ]
    Evaluated by the number of dose-limiting toxicities (DLT) graded using the NCI CTCAE v 4.03

  3. Phase 2: To assess progression-free survival (PFS) of ibrutinib in combination with everolimus in RCC, and ibrutinib in combination with paclitaxel for UC cohort 2. [ Time Frame: Approximately 12 months ]
    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.

  4. Phase 2: To assess the ORR of ibrutinib combination therapy in GC, CRC, UC cohort 6, and ibrutinib as a single agent in UC cohort 5 [ Time Frame: Approximately 12 months ]
    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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Phase 2: To assess the ORR of ibrutinib combination therapy in RCC and UC cohort 2. [ Time Frame: Approximately 12 months ]
    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.

  3. Phase 2: To assess the DOR in each cohort [ Time Frame: Approximately 12 months ]
    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.

  4. Phase 2: To assess the DCR in each cohort [ Time Frame: Approximately 12 months ]
    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.

  5. Phase 2: To assess the median OS of ibrutinib combination or single-agent therapy in each cohort [ Time Frame: Approximately 24 months ]
    Defined as the time from first dose of study drug to death due to any cause.



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02599324


Contacts
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Contact: Bhagyashree Yadav 669-224-1104 PCYC-1128@pcyc.com

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Locations
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United States, Alabama
Clearview Cancer Institute Recruiting
Huntsville, Alabama, United States, 35805
Contact: Investigator #0965         
United States, California
UC San Diego Moores Cancer Center Completed
La Jolla, California, United States, 92093
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Investigator #0209         
St. Mary's Medical Center Recruiting
San Francisco, California, United States, 94117
Contact: Investigator #969         
UCLA Recruiting
Santa Monica, California, United States, 90404
Contact: Investigator #1085         
United States, Connecticut
The Whittingham Cancer Center at Norwalk Hospital Completed
Norwalk, Connecticut, United States, 06856
United States, District of Columbia
Georgetown University Medical Center Completed
Washington, District of Columbia, United States, 20007
United States, Florida
Cancer Specialists of North Florida Recruiting
Jacksonville, Florida, United States, 32256
Contact: Investigator #1093         
United States, Indiana
Horizon Oncology Research, Inc Recruiting
Lafayette, Indiana, United States, 47905
Contact: Investigator #0337         
United States, Kansas
The University of Kansas Clinical Research Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Investigator #0706         
United States, Louisiana
East Jefferson General Hospital Recruiting
Metairie, Louisiana, United States, 70006
Contact: Investigator #1084         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Investigator #0016         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Investigator #0130         
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Investigator #0195         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Investigator #0229         
United States, New Mexico
San Juan Oncology Associates Recruiting
Farmington, New Mexico, United States, 87401
Contact: Investigator #1020         
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Investigator #0975         
United States, Pennsylvania
Penn State Hershey Cancer Institute Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Investigator #0220         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Investigator #0402         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Investigator #0024         
United States, Texas
The University of Texas Medical Branch (UTMB) - Cancer Center Completed
Galveston, Texas, United States, 77555
Scott & White Memorial Hospital Completed
Temple, Texas, United States, 76508
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Investigator #0972         
United States, Washington
Wenatchee Valley Hospital and Clinics Recruiting
Wenatchee, Washington, United States, 98802
Contact: Investigator #0894         
Korea, Republic of
Chonnam National University Hwasun Hospital Recruiting
Hwasun, Jeollanam-do, Korea, Republic of, 58128
Contact: Investigator #916         
Seoul National University Bundang Hospital Recruiting
Seongnam-si, Korea, Republic of, 13620
Contact: Investigator #982         
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Contact: Investigator #926         
Yonsei University Health System, Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Contact: Investigator #0927         
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Contact: Investigator #963         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Contact: Investigator #0925         
The Catholic University of Korea, Seoul St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 06591
Contact: Investigator #0928         
Korea University Guro Hospital Recruiting
Seoul, Korea, Republic of, 08308
Contact: Investigator #924         
Spain
Hospital Universitario Marques de Valdecilla (HUMV) Recruiting
Santander, Cantabria, Spain, 39008
Contact: Investigator #0973         
Institut Catala d'Oncologia Recruiting
Barcelona, Cataluna, Spain, 08916
Contact: Investigator #0984         
Hospital Universitario de Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Investigator #0534         
Hospital Universitari Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Investigator #0533         
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain, 28034
Contact: Investigator #0874         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Investigator #0864         
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Investigator #0921         
Hospital Universitario Virgen del Rocio (HUVR) Recruiting
Seville, Spain, 41013
Contact: Investigator #0863         
United Kingdom
The Royal Marsden Hospital Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Contact: Investigator #0543         
Beatson West of Scotland Cancer Center Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Investigator #0652         
Sarah Cannon Research Institute Recruiting
London, United Kingdom, W1G 6AD
Contact: Investigator #1079         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Contact: Investigator #0030         
Oxford University Hospitals NHS Trust Recruiting
Oxford, United Kingdom, OX3 7LE
Contact: Investigator #0814         
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
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Study Director: George Cole, M.D. Pharmacyclics LLC.

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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02599324     History of Changes
Other Study ID Numbers: PCYC-1128-CA
First Posted: November 6, 2015    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Adenocarcinoma
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
Urologic Diseases
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Pembrolizumab
Everolimus
Sirolimus
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs