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

Sponsor
Pharmacyclics LLC. (Industry)
Overall Status
Completed
CT.gov ID
NCT02599324
Collaborator
(none)
261
63
6
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Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
261 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 :
Nov 1, 2015
Actual Primary Completion Date :
Aug 20, 2021
Actual Study Completion Date :
Aug 20, 2021

Arms and Interventions

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 Ibrutinib- Enrollment Closed

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 - Enrollment Closed

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

Outcome Measures

Primary Outcome Measures

  1. Phase 1b: To determine the recommended Phase 2 dose (RP2D) of ibrutinib [Approximately 6 months after evaluation]

    Evaluated by the number of dose-limiting toxicities (DLT) graded using the NCI CTCAE v 4.03

  2. Phase 2: To assess progression-free survival (PFS) [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.

  3. Phase 2: To assess the overall response rate (ORR) [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.

  4. Number of Participants with Adverse Events [Approximately 24 months]]

    An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Secondary Outcome Measures

  1. To assess the safety and tolerability of ibrutinib combination or single agent [Approximately 12 months]

    Safety and tolerability of ibrutinib combination or single agent as measured by frequency and type of adverse events graded using NCI CTCAE v4.03

  2. To assess the disease control rate (DCR). [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

  3. Phase 2: To assess the duration of response (DOR) [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 median overall survival (OS) [Approximately 24 months]

    Defined as the time from first dose of study drug to death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
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 cohort 1 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 cohort 3 gastric or GEJ adenocarcinoma: minimum of 1 and maximum of 3 prior regimens one of which must have included a fluoropyrimidine regimen

  • For cohort 4 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Clearview Cancer Institute Huntsville Alabama United States 35805
2 Banner MD Anderson Cancer Centre Gilbert Arizona United States 85234
3 University of Arizona Cancer Center - Bannor Hospital Tucson Arizona United States 85724
4 UC San Diego Moores Cancer Center La Jolla California United States 92093
5 VA Long Beach Healthcare System Long Beach California United States 90822
6 University of Southern California Los Angeles California United States 90033
7 University of California Irvine Orange California United States 92868
8 St. Helena Hospital Saint Helena California United States 94574
9 Salinas Valley Memorial Healthcare System Salinas California United States 93901
10 St. Mary's Medical Center San Francisco California United States 94117
11 UCLA Santa Monica California United States 90404
12 St. Joseph Health Santa Rosa California United States 95403
13 The Whittingham Cancer Center at Norwalk Hospital Norwalk Connecticut United States 06856
14 Georgetown University Medical Center Washington District of Columbia United States 20007
15 Cancer Specialists of North Florida Jacksonville Florida United States 32256
16 Columbus Regional Research Institute, John B Amos Cancer Center-Research Dept. Columbus Georgia United States 31904
17 NorthShore University Health System-Evanston Evanston Illinois United States 60201
18 Franciscan Health Indianapolis Indianapolis Indiana United States 46237
19 Horizon Oncology Research, Inc Lafayette Indiana United States 47905
20 University of Iowa Hospitas and Clinics Iowa City Iowa United States 52242
21 The University of Kansas Clinical Research Center Fairway Kansas United States 66205
22 East Jefferson General Hospital Metairie Louisiana United States 70006
23 Tufts Medical Center Boston Massachusetts United States 02111
24 Karmanos Cancer Institute Detroit Michigan United States 48201
25 Henry Ford Hospital Detroit Michigan United States 48202
26 Central Care Cancer Center Bolivar Missouri United States 65613
27 Capital Region Medical Center, Goldschmidt Cancer Center Jefferson City Missouri United States 65109
28 Nebraska Methodist Hospital Omaha Nebraska United States 68114
29 New Jersey Hematology Oncology Associates (NJHOA) Brick New Jersey United States 08724
30 New Mexico Comprehensive Cancer Center Albuquerque New Mexico United States 87106
31 San Juan Oncology Associates Farmington New Mexico United States 87401
32 Memorial Sloan Kettering Cancer Center New York New York United States 10065
33 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157
34 Penn State Hershey Cancer Institute Hershey Pennsylvania United States 17033
35 University of Pennsylvania Philadelphia Pennsylvania United States 19104
36 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232
37 The University of Texas Medical Branch (UTMB) - Cancer Center Galveston Texas United States 77555
38 Scott & White Memorial Hospital Temple Texas United States 76508
39 Virginia Cancer Specialists Fairfax Virginia United States 22031
40 Virginia Mason Medical Center Seattle Washington United States 98101
41 University of Washington/Seattle Cancer Care Alliance Seattle Washington United States 98109
42 Wenatchee Valley Hospital and Clinics Wenatchee Washington United States 98802
43 Chonnam National University Hwasun Hospital Hwasun Jeollanam-do Korea, Republic of 58128
44 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13620
45 Seoul National University Hospital Seoul Korea, Republic of 03080
46 Yonsei University Health System, Severance Hospital Seoul Korea, Republic of 03722
47 Asan Medical Center Seoul Korea, Republic of 05505
48 Samsung Medical Center Seoul Korea, Republic of 06351
49 The Catholic University of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 06591
50 Korea University Guro Hospital Seoul Korea, Republic of 08308
51 Hospital Universitario Marques de Valdecilla (HUMV) Santander Cantabria Spain 39008
52 Hospital Universitario de Vall d'Hebron Barcelona Spain 08035
53 Hospital Universitari Clinic de Barcelona Barcelona Spain 08036
54 Institut Catala D'Oncologia Badalona Barcelona Spain 08916
55 Hospital Universitario Ramon y Cajal Madrid Spain 28034
56 Hospital Universitario 12 de Octubre Madrid Spain 28041
57 Hospital Universitario La Paz Madrid Spain 28046
58 Hospital Universitario Virgen del Rocio (HUVR) Seville Spain 41013
59 The Royal Marsden Hospital Sutton Surrey United Kingdom SM2 5PT
60 Beatson West of Scotland Cancer Center Glasgow United Kingdom G12 0YN
61 Sarah Cannon Research Institute London United Kingdom W1G 6AD
62 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
63 Oxford University Hospitals NHS Trust Oxford United Kingdom OX3 7LE

Sponsors and Collaborators

  • Pharmacyclics LLC.

Investigators

  • Study Director: Jim Dean, M.D., Pharmacyclics, an AbbVie Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT02599324
Other Study ID Numbers:
  • PCYC-1128-CA
First Posted:
Nov 6, 2015
Last Update Posted:
Mar 24, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 24, 2022