A Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Renal Cell Carcinoma - Enrollment Closed Phase 1b: Patients will receive ibrutinib at various dose levels in combination with everolimus to determine the Recommended Phase 2 Dose (RP2D) of ibrutinib. Phase 2: Patients will receive ibrutinib at the RP2D determined in Phase 1b in combination with everolimus. |
Drug: Ibrutinib
Drug: Everolimus
|
Experimental: Urothelial Carcinoma - Enrollment Closed Phase 1b: Patients will receive ibrutinib at various dose levels in combination with paclitaxel to determine the RP2D of ibrutinib. Phase 2: Subjects will receive paclitaxel at the RP2D determined in Phase 1b in combination with paclitaxel. |
Drug: Ibrutinib
Drug: Paclitaxel
|
Experimental: Gastric Adenocarcinoma - Enrollment Closed Phase 1b: Patients will receive ibrutinib at various dose levels in combination with docetaxel to determine the RP2D of ibrutinib. Phase 2: Subjects will receive docetaxel at the RP2D determined in Phase 1b in combination with docetaxel. |
Drug: Ibrutinib
Drug: Docetaxel
|
Experimental: Colorectal Adenocarcinoma - Enrollment Closed Phase 1b: Patients will receive ibrutinib at various dose levels in combination with cetuximab to determine RP2D of ibrutinib. Phase 2: Subjects will receive ibrutinib at the RP2D determined in Phase 1b in combination with cetuximab. |
Drug: Ibrutinib
Drug: Cetuximab
|
Experimental: Urothelial Carcinoma Ibrutinib- Enrollment Closed Phase 1b: Patients will receive ibrutinib at various dose levels to determine the RP2D of ibrutinib Phase 2: Subjects will receive ibrutinib at the RP2D determined in Phase 1b. |
Drug: Ibrutinib
|
Experimental: Urothelial Carcinoma with Pembrolizumab - Enrollment Closed Phase 1b: Patients will receive ibrutinib at various dose levels in combination with pembrolizumab to determine the RP2D of ibrutinib Phase 2: Subjects will receive ibrutinib at the RP2D determined in Phase 1b in combination with pembrolizumab. |
Drug: Ibrutinib
Drug: Pembrolizumab
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: To determine the recommended Phase 2 dose (RP2D) of ibrutinib [Approximately 6 months after evaluation]
Evaluated by the number of dose-limiting toxicities (DLT) graded using the NCI CTCAE v 4.03
- Phase 2: To assess progression-free survival (PFS) [Approximately 12 months]
Defined by the time from the date of first dose of study drug until confirmed disease progression based on investigator assessment, per RECIST 1.1, or death from any cause, whichever comes first.
- Phase 2: To assess the overall response rate (ORR) [Approximately 12 months]
Defined by the proportion of subjects with a best response of complete response (CR) or partial response (PR) by investigator assessment, per RECIST 1.1.
- Number of Participants with Adverse Events [Approximately 24 months]]
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Secondary Outcome Measures
- To assess the safety and tolerability of ibrutinib combination or single agent [Approximately 12 months]
Safety and tolerability of ibrutinib combination or single agent as measured by frequency and type of adverse events graded using NCI CTCAE v4.03
- To assess the disease control rate (DCR). [Approximately 12 months]
Defined by the proportion of subjects with a best response of complete response (CR), partial response (PR), stable disease (greater than or equal to 6 weeks) by investigator assessment, per RECIST 1.1
- Phase 2: To assess the duration of response (DOR) [Approximately 12 months]
Defined for responders as duration of time from initial response (CR or PR by investigator assessment) to first documentation of disease progression or death from any cause, whichever occurs first.
- Phase 2: To assess the median overall survival (OS) [Approximately 24 months]
Defined as the time from first dose of study drug to death due to any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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For cohort 1 RCC: minimum of 1 and maximum of 4 prior regimens, one or more of which must have included a VEGF-TKI
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For UC cohort 2: minimum of 1 and maximum of 2 prior regimens, one of which must have included a platinum-based regimen
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For UC cohort 5: Minimum of 1 and maximum of 2 prior regimens, one of which must have included a checkpoint inhibitor.
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For UC cohort 6:
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Locally advanced or mUC who are not eligible for cisplatin chemo with a PDL-1 score (CPS) of ≥ 10 without prior treatment.
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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.
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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
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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:
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Adequate hematologic function:
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Absolute neutrophil count ≥1500 cells/mm3 (1.5 x 109/L)
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Platelet count >80,000 cells/mm3 (80 x 109/L) for cohort 1 (RCC)
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Platelet counts >100,000 cells/mm3 (100 x 109/L) for all UC cohorts
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Hemoglobin ≥8.0 g/dL. for cohort 1 (RCC),all UC cohorts, and cohort 3 (GC)
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Hemoglobin ≥9.0 g/dL for cohort 4 (CRC)
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Adequate hepatic and renal function defined as:
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Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤5.0 x upper
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limit of normal (ULN) if liver metastases, or ≤3 x ULN without liver metastases
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Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases present
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Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic
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origin, such as hemolysis) with the exception of subjects in the GC cohort where
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docetaxel is administered, these subjects must have bilirubin within normal limits (WNL)
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Estimated Creatinine Clearance ≥30 mL/min (Cockcroft-Gault)
Exclusion Criteria
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Prior treatment with:
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Everolimus or temsirolimus (RCC cohort 1)
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Any taxane (UC cohort of ibrutinib + paclitaxel) (cohort 2)
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Checkpoint inhibitors (UC cohort 6)
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Any taxane (GC cohort 3)
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Cetuximab or panitumumab (CRC cohort 4)
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For all Cohorts:
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Concomitant use of warfarin or other Vitamin K antagonists
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History of stroke or intracranial hemorrhage within 6 months prior to enrollment
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Major surgery within 4 weeks of first dose of study drug
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Requires treatment with strong CYP3A inhibitors known bleeding disorders or hemophilia
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UC cohort 6 only:
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Subjects who have an active, known or suspected autoimmune disease.
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Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
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Non-steroid immunosuppressive medications within 14 days before the first dose of ibrutinib and pembrolizumab.
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Subjects in whom prior anti PD-1 / anti-PD-L1 therapy was intolerable and required discontinuation of treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clearview Cancer Institute | Huntsville | Alabama | United States | 35805 |
2 | Banner MD Anderson Cancer Centre | Gilbert | Arizona | United States | 85234 |
3 | University of Arizona Cancer Center - Bannor Hospital | Tucson | Arizona | United States | 85724 |
4 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
5 | VA Long Beach Healthcare System | Long Beach | California | United States | 90822 |
6 | University of Southern California | Los Angeles | California | United States | 90033 |
7 | University of California Irvine | Orange | California | United States | 92868 |
8 | St. Helena Hospital | Saint Helena | California | United States | 94574 |
9 | Salinas Valley Memorial Healthcare System | Salinas | California | United States | 93901 |
10 | St. Mary's Medical Center | San Francisco | California | United States | 94117 |
11 | UCLA | Santa Monica | California | United States | 90404 |
12 | St. Joseph Health | Santa Rosa | California | United States | 95403 |
13 | The Whittingham Cancer Center at Norwalk Hospital | Norwalk | Connecticut | United States | 06856 |
14 | Georgetown University Medical Center | Washington | District of Columbia | United States | 20007 |
15 | Cancer Specialists of North Florida | Jacksonville | Florida | United States | 32256 |
16 | Columbus Regional Research Institute, John B Amos Cancer Center-Research Dept. | Columbus | Georgia | United States | 31904 |
17 | NorthShore University Health System-Evanston | Evanston | Illinois | United States | 60201 |
18 | Franciscan Health Indianapolis | Indianapolis | Indiana | United States | 46237 |
19 | Horizon Oncology Research, Inc | Lafayette | Indiana | United States | 47905 |
20 | University of Iowa Hospitas and Clinics | Iowa City | Iowa | United States | 52242 |
21 | The University of Kansas Clinical Research Center | Fairway | Kansas | United States | 66205 |
22 | East Jefferson General Hospital | Metairie | Louisiana | United States | 70006 |
23 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
24 | Karmanos Cancer Institute | Detroit | Michigan | United States | 48201 |
25 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
26 | Central Care Cancer Center | Bolivar | Missouri | United States | 65613 |
27 | Capital Region Medical Center, Goldschmidt Cancer Center | Jefferson City | Missouri | United States | 65109 |
28 | Nebraska Methodist Hospital | Omaha | Nebraska | United States | 68114 |
29 | New Jersey Hematology Oncology Associates (NJHOA) | Brick | New Jersey | United States | 08724 |
30 | New Mexico Comprehensive Cancer Center | Albuquerque | New Mexico | United States | 87106 |
31 | San Juan Oncology Associates | Farmington | New Mexico | United States | 87401 |
32 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
33 | Wake Forest Baptist Health | Winston-Salem | North Carolina | United States | 27157 |
34 | Penn State Hershey Cancer Institute | Hershey | Pennsylvania | United States | 17033 |
35 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
36 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
37 | The University of Texas Medical Branch (UTMB) - Cancer Center | Galveston | Texas | United States | 77555 |
38 | Scott & White Memorial Hospital | Temple | Texas | United States | 76508 |
39 | Virginia Cancer Specialists | Fairfax | Virginia | United States | 22031 |
40 | Virginia Mason Medical Center | Seattle | Washington | United States | 98101 |
41 | University of Washington/Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109 |
42 | Wenatchee Valley Hospital and Clinics | Wenatchee | Washington | United States | 98802 |
43 | Chonnam National University Hwasun Hospital | Hwasun | Jeollanam-do | Korea, Republic of | 58128 |
44 | Seoul National University Bundang Hospital | Seongnam-si | Korea, Republic of | 13620 | |
45 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
46 | Yonsei University Health System, Severance Hospital | Seoul | Korea, Republic of | 03722 | |
47 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
48 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
49 | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Korea, Republic of | 06591 | |
50 | Korea University Guro Hospital | Seoul | Korea, Republic of | 08308 | |
51 | Hospital Universitario Marques de Valdecilla (HUMV) | Santander | Cantabria | Spain | 39008 |
52 | Hospital Universitario de Vall d'Hebron | Barcelona | Spain | 08035 | |
53 | Hospital Universitari Clinic de Barcelona | Barcelona | Spain | 08036 | |
54 | Institut Catala D'Oncologia Badalona | Barcelona | Spain | 08916 | |
55 | Hospital Universitario Ramon y Cajal | Madrid | Spain | 28034 | |
56 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
57 | Hospital Universitario La Paz | Madrid | Spain | 28046 | |
58 | Hospital Universitario Virgen del Rocio (HUVR) | Seville | Spain | 41013 | |
59 | The Royal Marsden Hospital | Sutton | Surrey | United Kingdom | SM2 5PT |
60 | Beatson West of Scotland Cancer Center | Glasgow | United Kingdom | G12 0YN | |
61 | Sarah Cannon Research Institute | London | United Kingdom | W1G 6AD | |
62 | The Christie NHS Foundation Trust | Manchester | United Kingdom | M20 4BX | |
63 | Oxford University Hospitals NHS Trust | Oxford | United Kingdom | OX3 7LE |
Sponsors and Collaborators
- Pharmacyclics LLC.
Investigators
- Study Director: Jim Dean, M.D., Pharmacyclics, an AbbVie Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PCYC-1128-CA