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BRIEF TITLE: Clinical Study of Ibrutinib monotherapy and Ibrutinib in combination with Pembrolizumab in patients with Bladder Cancer

A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors


  • Org Study ID: PCYC-1128-CA
  • Secondary ID:
  • NCT ID: NCT02599324
  • NCT Alias:
  • Sponsor: Pharmacyclics LLC. - Industry
  • Source: Pharmacyclics LLC.

Description

The purpose of this study is to evaluate the safety, tolerability, and efficacy of Ibrutinib monotherapy and the combination treatment of ibrutinib with Pembrolizumab in patients with Bladder Cancer. For more information, click here.

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.

Overal Status Start Date Phase Study Type
Recruiting November 2015 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - 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

Primary Outcome 1 - Time Frame: Approximately 6 months after evaluation

Primary Outcome 2 - Measure: Phase 1b: To confirm the RP2D of single-agent ibrutinib in UC cohort 5

Primary Outcome 2 - Time Frame: Approximately 6 months after evaluation

Primary Outcome 3 - Measure: 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.

Primary Outcome 3 - Time Frame: Approximately 12 months

Primary Outcome 4 - Measure: 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

Primary Outcome 4 - Time Frame: Approximately 12 months

Condition:

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

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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: George Cole, M.D.

Role: Study Director

Affiliation: Pharmacyclics LLC.

Overall Contact

Name: Bhagyashree Yadav

Phone: 669-224-1104

Email: PCYC-1128@pcyc.com

Locations

Facility Status Contact
Clearview Cancer Institute
Huntsville, Alabama 35805
United States
Recruiting Investigator #0965

UC San Diego Moores Cancer Center
La Jolla, California 92093
United States
Completed
University of Southern California
Los Angeles, California 90033
United States
Recruiting Investigator #0209

St. Mary's Medical Center
San Francisco, California 94117
United States
Recruiting Investigator #969

UCLA
Santa Monica, California 90404
United States
Recruiting Investigator #1085

The Whittingham Cancer Center at Norwalk Hospital
Norwalk, Connecticut 06856
United States
Completed
Georgetown University Medical Center
Washington, District of Columbia 20007
United States
Completed
Cancer Specialists of North Florida
Jacksonville, Florida 32256
United States
Recruiting Investigator #1093

Horizon Oncology Research, Inc
Lafayette, Indiana 47905
United States
Recruiting Investigator #0337

The University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
Recruiting Investigator #0706

East Jefferson General Hospital
Metairie, Louisiana 70006
United States
Recruiting Investigator #1084

Tufts Medical Center
Boston, Massachusetts 02111
United States
Recruiting Investigator #0016

Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Recruiting Investigator #0130

Henry Ford Hospital
Detroit, Michigan 48202
United States
Recruiting Investigator #0195

Nebraska Methodist Hospital
Omaha, Nebraska 68114
United States
Recruiting Investigator #0229

San Juan Oncology Associates
Farmington, New Mexico 87401
United States
Recruiting Investigator #1020

Wake Forest Baptist Health
Winston-Salem, North Carolina 27157
United States
Recruiting Investigator #0975

Penn State Hershey Cancer Institute
Hershey, Pennsylvania 17033
United States
Recruiting Investigator #0220

University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Recruiting Investigator #0402

Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232
United States
Recruiting Investigator #0024

The University of Texas Medical Branch (UTMB) - Cancer Center
Galveston, Texas 77555
United States
Completed
Scott & White Memorial Hospital
Temple, Texas 76508
United States
Completed
Virginia Cancer Specialists
Fairfax, Virginia 22031
United States
Recruiting Investigator #0972

Wenatchee Valley Hospital and Clinics
Wenatchee, Washington 98802
United States
Recruiting Investigator #0894

Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do 58128
Korea, Republic of
Recruiting Investigator #916

Seoul National University Bundang Hospital
Seongnam-si, 13620
Korea, Republic of
Recruiting Investigator #982

Seoul National University Hospital
Seoul, 03080
Korea, Republic of
Recruiting Investigator #926

Yonsei University Health System, Severance Hospital
Seoul, 03722
Korea, Republic of
Recruiting Investigator #0927

Asan Medical Center
Seoul, 05505
Korea, Republic of
Recruiting Investigator #963

Samsung Medical Center
Seoul, 06351
Korea, Republic of
Recruiting Investigator #0925

The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
Korea, Republic of
Recruiting Investigator #0928

Korea University Guro Hospital
Seoul, 08308
Korea, Republic of
Recruiting Investigator #924

Hospital Universitario Marques de Valdecilla (HUMV)
Santander, Cantabria 39008
Spain
Recruiting Investigator #0973

Institut Catala d'Oncologia
Barcelona, Cataluna 08916
Spain
Recruiting Investigator #0984

Hospital Universitario de Vall d'Hebron
Barcelona, 08035
Spain
Recruiting Investigator #0534

Hospital Universitari Clinic de Barcelona
Barcelona, 08036
Spain
Recruiting Investigator #0533

Hospital Universitario Ramon y Cajal
Madrid, 28034
Spain
Recruiting Investigator #0874

Hospital Universitario 12 de Octubre
Madrid, 28041
Spain
Recruiting Investigator #0864

Hospital Universitario La Paz
Madrid, 28046
Spain
Recruiting Investigator #0921

Hospital Universitario Virgen del Rocio (HUVR)
Seville, 41013
Spain
Recruiting Investigator #0863

The Royal Marsden Hospital
Sutton, Surrey SM2 5PT
United Kingdom
Recruiting Investigator #0543

Beatson West of Scotland Cancer Center
Glasgow, G12 0YN
United Kingdom
Recruiting Investigator #0652

Sarah Cannon Research Institute
London, W1G 6AD
United Kingdom
Recruiting Investigator #1079

The Christie NHS Foundation Trust
Manchester, M20 4BX
United Kingdom
Recruiting Investigator #0030

Oxford University Hospitals NHS Trust
Oxford, OX3 7LE
United Kingdom
Recruiting Investigator #0814