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Brief Title: Ibrutinib Combination Therapy in Selected Advanced Urothelial or Bladder Cancer Tumors

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

INTRODUCTION

  • Org Study ID: PCYC-1128-CA
  • Secondary ID: N/A
  • NCT ID: NCT02599324
  • Sponsor: 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.


  • Overall Status
    Recruiting
  • Start Date
    November 2015
  • Phase
    Phase 1/Phase 2
  • Study Type
    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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: Approximately 12 months

CONDITION

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

ELIGIBILITY


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.

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: George Cole, M.D.

Role: Study Director

Affiliation: Pharmacyclics LLC.

Overall Contact

Name: George Cole, M.D.

Phone: 669-224-1104

Email: PCYC-1128@pcyc.com

LOCATION

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

Facility: University of Southern California
Los Angeles, California 90033
United States
Status: Recruiting Contact: Investigator #0209

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

Facility: UCLA
Santa Monica, California 90404
United States
Status: Recruiting Contact: Investigator #1085

Facility: Cancer Specialists of North Florida
Jacksonville, Florida 32256
United States
Status: Recruiting Contact: Investigator #1093

Facility: Horizon Oncology Research, Inc
Lafayette, Indiana 47905
United States
Status: Recruiting Contact: Investigator #0337

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

Facility: East Jefferson General Hospital
Metairie, Louisiana 70006
United States
Status: Recruiting Contact: Investigator #1084

Facility: Tufts Medical Center
Boston, Massachusetts 02111
United States
Status: Recruiting Contact: Investigator #0016

Facility: Karmanos Cancer Institute
Detroit, Michigan 48201
United States
Status: Recruiting Contact: Investigator #0130

Facility: Henry Ford Hospital
Detroit, Michigan 48202
United States
Status: Recruiting Contact: Investigator #0195

Facility: Nebraska Methodist Hospital
Omaha, Nebraska 68114
United States
Status: Recruiting Contact: Investigator #0229

Facility: San Juan Oncology Associates
Farmington, New Mexico 87401
United States
Status: Recruiting Contact: Investigator #1020

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

Facility: Penn State Hershey Cancer Institute
Hershey, Pennsylvania 17033
United States
Status: Recruiting Contact: Investigator #0220

Facility: University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Status: Recruiting Contact: Investigator #0402

Facility: Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232
United States
Status: Recruiting Contact: Investigator #0024

Facility: Virginia Cancer Specialists
Fairfax, Virginia 22031
United States
Status: Recruiting Contact: Investigator #0972

Facility: Wenatchee Valley Hospital and Clinics
Wenatchee, Washington 98802
United States
Status: Recruiting Contact: Investigator #0894

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

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

Facility: Seoul National University Hospital
Seoul, 03080
Korea, Republic of
Status: Recruiting Contact: Investigator #926

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

Facility: Asan Medical Center
Seoul, 05505
Korea, Republic of
Status: Recruiting Contact: Investigator #963

Facility: Samsung Medical Center
Seoul, 06351
Korea, Republic of
Status: Recruiting Contact: Investigator #0925

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

Facility: Korea University Guro Hospital
Seoul, 08308
Korea, Republic of
Status: Recruiting Contact: Investigator #924

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

Facility: Institut Catala d'Oncologia
Barcelona, Cataluna 08916
Spain
Status: Recruiting Contact: Investigator #0984

Facility: Hospital Universitario de Vall d'Hebron
Barcelona, 08035
Spain
Status: Recruiting Contact: Investigator #0534

Facility: Hospital Universitari Clinic de Barcelona
Barcelona, 08036
Spain
Status: Recruiting Contact: Investigator #0533

Facility: Hospital Universitario Ramon y Cajal
Madrid, 28034
Spain
Status: Recruiting Contact: Investigator #0874

Facility: Hospital Universitario 12 de Octubre
Madrid, 28041
Spain
Status: Recruiting Contact: Investigator #0864

Facility: Hospital Universitario La Paz
Madrid, 28046
Spain
Status: Recruiting Contact: Investigator #0921

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

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

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

Facility: Sarah Cannon Research Institute
London, W1G 6AD
United Kingdom
Status: Recruiting Contact: Investigator #1079

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

Facility: Oxford University Hospitals NHS Trust
Oxford, OX3 7LE
United Kingdom
Status: Recruiting Contact: Investigator #0814