Ibrutinib Combination Therapy in Selected Advanced Urothelial or Bladder Cancer Tumors

INTRODUCTION

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

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 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

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

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

Name: George Cole, M.D.

Role: Study Director

Affiliation: Pharmacyclics LLC.

Name: George Cole, M.D.

Phone: 669-224-1104

Email: PCYC-1128@pcyc.com

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

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

BRIEF SUMMARY

PRIMARY OUTCOMES

CONDITION

ELIGIBILITY

OFFICIAL INFORMATION

Overall Contact

LOCATION

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