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

NCT ID: NCT02599324

Last Updated: 2023-11-18

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

263 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-01

Study Completion Date

2021-08-20

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort 1: Renal Cell Carcinoma (RCC)

Phase 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.

Group Type EXPERIMENTAL

ibrutinib

Intervention Type DRUG

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

everolimus

Intervention Type DRUG

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.

Cohort 2: Urothelial Carcinoma (UC)

Phase 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.

Group Type EXPERIMENTAL

ibrutinib

Intervention Type DRUG

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

paclitaxel

Intervention Type DRUG

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.

Cohort 3: Gastric Adenocarcinoma (GA or GC)

Phase 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.

Group Type EXPERIMENTAL

ibrutinib

Intervention Type DRUG

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

docetaxel

Intervention Type DRUG

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.

Cohort 4: Colorectal Adenocarcinoma (CRC)

Phase 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.

Group Type EXPERIMENTAL

ibrutinib

Intervention Type DRUG

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

cetuximab

Intervention Type DRUG

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.

Cohort 5: Urothelial Carcinoma (UC) Ibrutinib

Phase 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.

Group Type EXPERIMENTAL

ibrutinib

Intervention Type DRUG

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

Cohort 6: Urothelial Carcinoma (UC) With Pembrolizumab

Phase 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.

Group Type EXPERIMENTAL

ibrutinib

Intervention Type DRUG

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

pembrolizumab

Intervention Type DRUG

Pembrolizumab 200 mg intravenous (IV) every 3 weeks.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

ibrutinib

Ibrutinib administered orally once daily with 8 ounces (approximately 240 mL) of water.

Intervention Type DRUG

everolimus

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.

Intervention Type DRUG

paclitaxel

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.

Intervention Type DRUG

docetaxel

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.

Intervention Type DRUG

cetuximab

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.

Intervention Type DRUG

pembrolizumab

Pembrolizumab 200 mg intravenous (IV) every 3 weeks.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Pharmacyclics LLC.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Pharmacyclics LLC

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Clearview Cancer Institute /ID# 1128-0965

Huntsville, Alabama, United States

Site Status

Banner MD Anderson Cancer Center /ID# 1128-0802

Gilbert, Arizona, United States

Site Status

University of Arizona Cancer Center - Tucson /ID# 1128-1546

Tucson, Arizona, United States

Site Status

Alta Bates Comprehensive Cancer Center /ID# 1128-0135

Berkeley, California, United States

Site Status

St Marys Medical Center /ID# 1128-0969

Daly City, California, United States

Site Status

Duplicate_University of California San Diego/ Moores Cancer Center /ID# 1128-0241

La Jolla, California, United States

Site Status

VA Long Beach Healthcare System /ID# 1128-0480

Long Beach, California, United States

Site Status

USC Norris Cancer Center /ID# 1128-0209

Los Angeles, California, United States

Site Status

UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 1128-0008

Orange, California, United States

Site Status

Salinas Valley Memorial Hosp /ID# 1128-0482

Salinas, California, United States

Site Status

Premiere Oncology, A Medical Corporation /ID# 1128-1085

Santa Monica, California, United States

Site Status

St. Joseph Health /ID# 1128-1462

Santa Rosa, California, United States

Site Status

Gregory Smith, MD (Private Practice) /ID# 1128-0419

St. Helena, California, United States

Site Status

Whittingham Cancer Center at Norwalk Hospital /ID# 1128-0411

Norwalk, Connecticut, United States

Site Status

Georgetown University Hospital /ID# 1128-0824

Washington D.C., District of Columbia, United States

Site Status

Duplicate_Cancer Specialist of North Florida (CSNF) ( R ) /ID# 1128-1093

Jacksonville, Florida, United States

Site Status

IACT Health-Columbus /ID# 1128-1389

Columbus, Georgia, United States

Site Status

Northshore Kellogg Cancer Center /ID# 1128-0484

Evanston, Illinois, United States

Site Status

Franciscan Health Indianapolis /ID# 1128-1125

Indianapolis, Indiana, United States

Site Status

Horizon Oncology Research Center /ID# 1128-0337

Lafayette, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics /ID# 1128-0766

Iowa City, Iowa, United States

Site Status

The University of Kansas Cancer Center /ID# 1128-0706

Fairway, Kansas, United States

Site Status

East Jefferson General Hospital /ID# 1128-1084

Metairie, Louisiana, United States

Site Status

Duplicate_Tufts Medical Center /ID# 1128-0016

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer In /ID# 1128-0130

Detroit, Michigan, United States

Site Status

Henry Ford Hospital /ID# 1128-0195

Detroit, Michigan, United States

Site Status

Central Care Cancer Center /ID# 1128-1596

Bolivar, Missouri, United States

Site Status

Capital Region Medical Center /ID# 1128-1412

Jefferson City, Missouri, United States

Site Status

Nebraska Methodist Hospital /ID# 1128-0229

Omaha, Nebraska, United States

Site Status

New Jersey Center for Cancer Research /ID# 1128-0493

Brick, New Jersey, United States

Site Status

Duplicate_New Mexico Cancer Care Alliance /ID# 1128-0938

Albuquerque, New Mexico, United States

Site Status

San Juan Oncology Associates /ID# 1128-1020

Farmington, New Mexico, United States

Site Status

Memorial Sloan Kettering Cancer Center-Koch Center /ID# 1128-0091

New York, New York, United States

Site Status

Wake Forest Univ HS /ID# 1128-0975

Winston-Salem, North Carolina, United States

Site Status

Oregon Health & Science University /ID# 1128-0251

Portland, Oregon, United States

Site Status

Penn State Hershey Medical Ctr /ID# 1128-0220

Hershey, Pennsylvania, United States

Site Status

Abramson Cancer Center of the Univ. of Pennsylvania /ID# 1128-0402

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Infectious Disease Clinic /ID# 1128-0024

Nashville, Tennessee, United States

Site Status

The University of Texas Medical Branch (UTMB) - Cancer Center - Galves /ID# 1128-0974

Galveston, Texas, United States

Site Status

Duplicate_Scott & White Mem Hosp & Clin /ID# 1128-0046

Temple, Texas, United States

Site Status

Duplicate_Virginia Cancer Specialists - Fairfax Office /ID# 1128-0972

Fairfax, Virginia, United States

Site Status

Virginia Mason Medical Center /ID# 1128-0005

Seattle, Washington, United States

Site Status

University of Washington /ID# 1128-1382

Seattle, Washington, United States

Site Status

Confluence Health /ID# 1128-0894

Wenatchee, Washington, United States

Site Status

Seoul National University Bundang Hospital /ID# 1128-0982

Seongnam, Gyeonggido, South Korea

Site Status

Yonsei University Health System Severance Hospital /ID# 1128-0927

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Chonnam National University Hwasun Hospital /ID# 1128-0916

Jeonnam, , South Korea

Site Status

Seoul National University Hospital /ID# 1128-0926

Seoul, , South Korea

Site Status

Asan Medical Center /ID# 1128-0963

Seoul, , South Korea

Site Status

Samsung Medical Center /ID# 1128-0925

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital /ID# 1128-0928

Seoul, , South Korea

Site Status

Korea University Guro Hospital /ID# 1128-0924

Seoul, , South Korea

Site Status

Instituto Catalan de Oncologia (ICO) Badalona /ID# 1128-0984

Badalona, Barcelona, Spain

Site Status

Hospital Unversitario Marques de Valdecilla /ID# 1128-0973

Santander, Cantabria, Spain

Site Status

Hospital Universitario Vall d'Hebron /ID# 1128-0534

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona /ID# 1128-0533

Barcelona, , Spain

Site Status

Hospital Universitario Ramon y Cajal /ID# 1128-0874

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre /ID# 1128-0864

Madrid, , Spain

Site Status

Hospital Universitario La Paz /ID# 1128-0921

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio /ID# 1128-0863

Seville, , Spain

Site Status

Sarah Cannon Research Institute /ID# 1128-1079

London, England, United Kingdom

Site Status

Duplicate_Beatson west of scotland cancer center /ID# 1128-0652

Glasgow, Scotland, United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust /ID# 1128-0543

London, , United Kingdom

Site Status

The Christie Hospital /ID# 1128-0030

Manchester, , United Kingdom

Site Status

Duplicate_Oxford University Hospitals NHS Trust /ID# 1128-0814

Oxford, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States South Korea Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 37919668 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2015-003656-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PCYC-1128-CA

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.