A Study to Evaluate Ibrutinib Combination Therapy in Patients With Selected Gastrointestinal and Genitourinary Tumors
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| ClinicalTrials.gov Identifier: NCT02599324 |
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Recruitment Status :
Completed
First Posted : November 6, 2015
Last Update Posted : March 24, 2022
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Sponsor:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Pharmacyclics LLC.
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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 |
|---|---|---|
| Metastatic Renal Cell Carcinoma Advanced Urothelial Carcinoma Advanced Gastric Adenocarcinoma Metastatic Colorectal Adenocarcinoma | Drug: Ibrutinib Drug: Everolimus Drug: Docetaxel Drug: Paclitaxel Drug: Cetuximab Drug: Pembrolizumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 261 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal And Genitourinary Tumors |
| Actual Study Start Date : | November 2015 |
| Actual Primary Completion Date : | August 20, 2021 |
| Actual Study Completion Date : | August 20, 2021 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Ibrutinib
| Arm | Intervention/treatment |
|---|---|
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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 |
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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 |
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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 |
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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 |
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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.
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Drug: Ibrutinib |
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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.
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Drug: Ibrutinib Drug: Pembrolizumab |
Primary Outcome Measures :
- Phase 1b: To determine the recommended Phase 2 dose (RP2D) of ibrutinib [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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). [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Approximately 24 months ]Defined as the time from first dose of study drug to death due to any cause.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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.
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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:
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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)
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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
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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)
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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
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02599324
Locations
Show 63 study locations
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
| Study Director: | Jim Dean, M.D. | Pharmacyclics, an AbbVie Company |
| Responsible Party: | Pharmacyclics LLC. |
| ClinicalTrials.gov Identifier: | NCT02599324 |
| Other Study ID Numbers: |
PCYC-1128-CA |
| First Posted: | November 6, 2015 Key Record Dates |
| Last Update Posted: | March 24, 2022 |
| Last Verified: | March 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma Adenocarcinoma Carcinoma, Renal Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Kidney Diseases Urologic Diseases Paclitaxel Docetaxel |
Pembrolizumab Everolimus Cetuximab Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |