Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal and Genitourinary Tumors
2 other identifiers
interventional
263
4 countries
65
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 advance gastrointestinal and genitourinary tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2015
Longer than P75 for phase_1
65 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 4, 2015
CompletedFirst Posted
Study publicly available on registry
November 6, 2015
CompletedStudy Start
First participant enrolled
December 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 20, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 20, 2021
CompletedResults Posted
Study results publicly available
October 26, 2022
CompletedNovember 18, 2023
September 1, 2022
5.7 years
November 4, 2015
August 16, 2022
November 14, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cohorts 1 to 6
A DLT was defined as any Grade 3 (severe) or higher non-hematologic or Grade 4 (life-threatening) hematologic adverse event (AE) occurring during the DLT observation period that was considered to be at least possibly related to the study treatment (ibrutinib or drug combination).
21 days after the initiation of therapy at the start of Cycle 1
Phase 1b/2 RP2D: Progression-Free Survival (PFS) as Assessed by Investigator in Cohorts 1 and 2
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of progressive disease (PD) or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.
Maximum time on study for Cohort 1 (Phase 1b/2 RP2D) was 37.4 months; for Cohort 2 (Phase 1b/2 RP2D) was 44.7 months.
Phase 1b/2 RP2D: Overall Response Rate (ORR) as Assessed by Investigator in Cohorts 3 to 6
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. CR: The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Normalization of tumor marker level, if relevant. All lymph nodes must be non-pathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Maximum time on study (Phase 1b/2 RP2D) for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
Secondary Outcomes (15)
Phase 1b: ORR in Cohorts 1 to 6
Maximum time on study (Phase 1b only) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 34.2 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
Phase 1b: Disease Control Rate (DCR) in Cohorts 1 to 6
Maximum time on study (Phase 1b only) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 34.2 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
Phase 1b/2 RP2D: DCR in Cohorts 1 to 6
Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
Phase 1b/2 RP2D: PFS in Cohorts 3 to 6
Maximum time on study (Phase 1b/2 RP2D) for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
Phase 1b/2 RP2D: ORR in Cohorts 1 and 2
Maximum time on study for Cohort 1 (Phase 1b/2 RP2D) was 37.4 months; for Cohort 2 (Phase 1b/2 RP2D) was 44.7 months. (Reverse Kaplan-Meier estimates)
- +10 more secondary outcomes
Study Arms (6)
Cohort 1: Renal Cell Carcinoma (RCC)
EXPERIMENTALPhase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of everolimus to determine the recommended phase 2 dose (RP2D) of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in phase 1b in combination with everolimus.
Cohort 2: Urothelial Carcinoma (UC)
EXPERIMENTALPhase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of paclitaxel to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with paclitaxel.
Cohort 3: Gastric Adenocarcinoma (GA or GC)
EXPERIMENTALPhase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of docetaxel to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive docetaxel at the RP2D determined in Phase 1b in combination with docetaxel.
Cohort 4: Colorectal Adenocarcinoma (CRC)
EXPERIMENTALPhase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of cetuximab to determine RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with cetuximab.
Cohort 5: Urothelial Carcinoma (UC) Ibrutinib
EXPERIMENTALPhase 1b: Participants receive ibrutinib at various dose levels to determine the RP2D of ibrutinib.(The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b.
Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab
EXPERIMENTALPhase 1b: Participants receive ibrutinib at various dose levels in combination with a fixed dose of pembrolizumab to determine the RP2D of ibrutinib. (The RP2D was determined for each cohort separately.) Phase 2: Participants receive ibrutinib at the RP2D determined in Phase 1b in combination with pembrolizumab.
Interventions
Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.
Everolimus 10 mg tablets should be taken orally once daily at the same time every day, either consistently with food or consistently without food. Four (4) x 2.5 mg tablets or two (2) x 5.0 mg tablets may be substituted if 10 mg tablet strength is not available.
Paclitaxel should be administered as a 60-minute (±10 minutes) infusion. Paclitaxel should be given at a dose level of 80 mg/m\^2, once weekly, in continual 3 weekly cycles.
Docetaxel administered as a 60 minute infusion (±10 minutes) at a dose level of 60 - 75 mg/m\^2 (according to local institutional standard of care), given continually in 21-day cycles.
Cetuximab 400 mg/m\^2 administered as a 120-minute IV infusion. The recommended subsequent weekly dose (all other infusions) is 250 mg/m\^2 infused over 60 minutes.
Pembrolizumab 200 mg intravenous (IV) every 3 weeks.
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (65)
Clearview Cancer Institute /ID# 1128-0965
Huntsville, Alabama, 35805, United States
Banner MD Anderson Cancer Center /ID# 1128-0802
Gilbert, Arizona, 85234, United States
University of Arizona Cancer Center - Tucson /ID# 1128-1546
Tucson, Arizona, 85724, United States
Alta Bates Comprehensive Cancer Center /ID# 1128-0135
Berkeley, California, 94704, United States
St Marys Medical Center /ID# 1128-0969
Daly City, California, 94015, United States
Duplicate_University of California San Diego/ Moores Cancer Center /ID# 1128-0241
La Jolla, California, 92037-0845, United States
VA Long Beach Healthcare System /ID# 1128-0480
Long Beach, California, 90822-5201, United States
USC Norris Cancer Center /ID# 1128-0209
Los Angeles, California, 90033, United States
UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1128-0008
Orange, California, 92868-3201, United States
Salinas Valley Memorial Hosp /ID# 1128-0482
Salinas, California, 93901, United States
Premiere Oncology, A Medical Corporation /ID# 1128-1085
Santa Monica, California, 90404, United States
St. Joseph Health /ID# 1128-1462
Santa Rosa, California, 95403, United States
Gregory Smith, MD (Private Practice) /ID# 1128-0419
St. Helena, California, 94574, United States
Whittingham Cancer Center at Norwalk Hospital /ID# 1128-0411
Norwalk, Connecticut, 06856-3852, United States
Georgetown University Hospital /ID# 1128-0824
Washington D.C., District of Columbia, 20007, United States
Duplicate_Cancer Specialist of North Florida (CSNF) ( R ) /ID# 1128-1093
Jacksonville, Florida, 32207, United States
IACT Health-Columbus /ID# 1128-1389
Columbus, Georgia, 31904-8946, United States
Northshore Kellogg Cancer Center /ID# 1128-0484
Evanston, Illinois, 60201, United States
Franciscan Health Indianapolis /ID# 1128-1125
Indianapolis, Indiana, 46237, United States
Horizon Oncology Research Center /ID# 1128-0337
Lafayette, Indiana, 47905, United States
University of Iowa Hospitals and Clinics /ID# 1128-0766
Iowa City, Iowa, 52242, United States
The University of Kansas Cancer Center /ID# 1128-0706
Fairway, Kansas, 66205, United States
East Jefferson General Hospital /ID# 1128-1084
Metairie, Louisiana, 70006, United States
Duplicate_Tufts Medical Center /ID# 1128-0016
Boston, Massachusetts, 02111-1552, United States
Barbara Ann Karmanos Cancer In /ID# 1128-0130
Detroit, Michigan, 48201, United States
Henry Ford Hospital /ID# 1128-0195
Detroit, Michigan, 48202, United States
Central Care Cancer Center /ID# 1128-1596
Bolivar, Missouri, 65613, United States
Capital Region Medical Center /ID# 1128-1412
Jefferson City, Missouri, 65102, United States
Nebraska Methodist Hospital /ID# 1128-0229
Omaha, Nebraska, 68114, United States
New Jersey Center for Cancer Research /ID# 1128-0493
Brick, New Jersey, 08724, United States
Duplicate_New Mexico Cancer Care Alliance /ID# 1128-0938
Albuquerque, New Mexico, 87106, United States
San Juan Oncology Associates /ID# 1128-1020
Farmington, New Mexico, 87401, United States
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 1128-0091
New York, New York, 10065-6007, United States
Wake Forest Univ HS /ID# 1128-0975
Winston-Salem, North Carolina, 27157, United States
Oregon Health & Science University /ID# 1128-0251
Portland, Oregon, 97239-3011, United States
Penn State Hershey Medical Ctr /ID# 1128-0220
Hershey, Pennsylvania, 17033-2360, United States
Abramson Cancer Center of the Univ. of Pennsylvania /ID# 1128-0402
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt Infectious Disease Clinic /ID# 1128-0024
Nashville, Tennessee, 37232, United States
The University of Texas Medical Branch (UTMB) - Cancer Center - Galves /ID# 1128-0974
Galveston, Texas, 77555-0565, United States
Duplicate_Scott & White Mem Hosp & Clin /ID# 1128-0046
Temple, Texas, 76508, United States
Duplicate_Virginia Cancer Specialists - Fairfax Office /ID# 1128-0972
Fairfax, Virginia, 22031, United States
Virginia Mason Medical Center /ID# 1128-0005
Seattle, Washington, 98101, United States
University of Washington /ID# 1128-1382
Seattle, Washington, 98109, United States
Confluence Health /ID# 1128-0894
Wenatchee, Washington, 98801, United States
Seoul National University Bundang Hospital /ID# 1128-0982
Seongnam, Gyeonggido, 13620, South Korea
Yonsei University Health System Severance Hospital /ID# 1128-0927
Seoul, Seoul Teugbyeolsi, 03722, South Korea
Chonnam National University Hwasun Hospital /ID# 1128-0916
Jeonnam, 58128, South Korea
Seoul National University Hospital /ID# 1128-0926
Seoul, 03080, South Korea
Asan Medical Center /ID# 1128-0963
Seoul, 05505, South Korea
Samsung Medical Center /ID# 1128-0925
Seoul, 06351, South Korea
The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 1128-0928
Seoul, 06591, South Korea
Korea University Guro Hospital /ID# 1128-0924
Seoul, 08308, South Korea
Instituto Catalan de Oncologia (ICO) Badalona /ID# 1128-0984
Badalona, Barcelona, 08916, Spain
Hospital Unversitario Marques de Valdecilla /ID# 1128-0973
Santander, Cantabria, 39008, Spain
Hospital Universitario Vall d'Hebron /ID# 1128-0534
Barcelona, 08035, Spain
Hospital Clinic de Barcelona /ID# 1128-0533
Barcelona, 08036, Spain
Hospital Universitario Ramon y Cajal /ID# 1128-0874
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre /ID# 1128-0864
Madrid, 28041, Spain
Hospital Universitario La Paz /ID# 1128-0921
Madrid, 28046, Spain
Hospital Universitario Virgen del Rocio /ID# 1128-0863
Seville, 41013, Spain
Sarah Cannon Research Institute /ID# 1128-1079
London, England, W1G 6AD, United Kingdom
Duplicate_Beatson west of scotland cancer center /ID# 1128-0652
Glasgow, Scotland, G12 0YN, United Kingdom
The Royal Marsden NHS Foundation Trust /ID# 1128-0543
London, SW3 6JJ, United Kingdom
The Christie Hospital /ID# 1128-0030
Manchester, M20 4BX, United Kingdom
Duplicate_Oxford University Hospitals NHS Trust /ID# 1128-0814
Oxford, OX3 7LE, United Kingdom
Related Publications (1)
Oh DY, Maqueda MA, Quinn DI, O'Dwyer PJ, Chau I, Kim SY, Duran I, Castellano D, Berlin J, Mellado B, Williamson SK, Lee KW, Marti F, Mathew P, Saif MW, Wang D, Chong E, Hilger-Rolfe J, Dean JP, Arkenau HT. Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study. BMC Cancer. 2023 Nov 3;23(1):1056. doi: 10.1186/s12885-023-11539-1.
PMID: 37919668DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
Pharmacyclics LLC
Pharmacyclics LLC.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 4, 2015
First Posted
November 6, 2015
Study Start
December 1, 2015
Primary Completion
August 20, 2021
Study Completion
August 20, 2021
Last Updated
November 18, 2023
Results First Posted
October 26, 2022
Record last verified: 2022-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at the following link.