REVOLUTION: Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma
Study Details
Study Description
Brief Summary
This trial is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of first-line chemo-immunotherapy combinations in participants with metastatic pancreatic ductal adenocarcinoma (mPDAC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is an open-label, non-randomized, exploratory platform trial designed to assess the safety and antitumor activity of immunotherapy, in combination with standard of care chemotherapy, in participants with mPDAC who have not received prior therapy. Where supportive mechanistic data are available, immunotherapy may also be combined with other treatment modalities (eg, radiation). Each cohort of this platform trial will test a different immunotherapy combination and consist of up to 2 stages: an initial stage (Stage 1) to evaluate safety, biomarkers, and/or clinical activity of the combination and an expanded cohort (Stage 2), when warranted, based on the safety, clinical activity, and/or biomarker results from Stage 1. The Sponsor intends to modify and/or add new combinations to the protocol as data emerge from scientific findings, in this and other trials.
This trial will be conducted in participants with histologically or cytologically documented diagnosis of mPDAC, with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, who have not received prior systemic therapy for their disease in the metastatic setting. Participants must have adequate organ and hematologic function and acceptable performance status. Participants must consent to tumor biopsies, including a pre-treatment (baseline) and on-treatment samples.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: Nivolumab + Ipilimumab + nP/gem
|
Drug: Nivolumab (Cohort A)
Nivolumab will be administered intravenously every 3 weeks for up to 2 years.
Other Names:
Drug: Ipilimumab (Cohort A and B)
Ipilimumab will be administered intravenously every 6 weeks for up to 2 cycles.
Other Names:
Drug: Nab-paclitaxel (nP) (Cohort A and B)
Nab-paclitaxel will be administered intravenously at 125 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.
Other Names:
Drug: Gemcitabine (gem) (Cohort A and B)
Gemcitabine will be administered intravenously at 1000 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.
Other Names:
|
| Experimental: Cohort B: Hydroxychloroquine + Ipilimumab + nP/gem
|
Drug: Ipilimumab (Cohort A and B)
Ipilimumab will be administered intravenously every 6 weeks for up to 2 cycles.
Other Names:
Drug: Hydroxychloroquine (HCQ) (Cohort B)
Hydroxychloroquine will be administered orally daily for up to 2 years.
Other Names:
Drug: Nab-paclitaxel (nP) (Cohort A and B)
Nab-paclitaxel will be administered intravenously at 125 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.
Other Names:
Drug: Gemcitabine (gem) (Cohort A and B)
Gemcitabine will be administered intravenously at 1000 mg/m2 for 2 weeks on and 1 week off, for at least 24 weeks, unless treatment discontinuation criteria are met.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence and severity of adverse events [Up to 2.5 years]
Secondary Outcome Measures
- Objective response rate (ORR) [Up to 2.5 years]
Defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Disease control rate (DCR) [At 9 months]
Defined as the proportion of participants who achieve confirmed CR or PR or stable disease (SD) lasting at least 16 weeks
- Duration of response (DOR) [Up to 2.5 years]
Defined as the time from first documentation of response (CR or PR) to first radiographic documentation of progressive disease (PD) or death due to any cause.
- Progression-free survival (PFS) [Up to 2.5 years]
Defined as the time from initiation of study intervention to date of first documented radiographic progression of disease or death due to any cause.
- Overall survival (OS) [Up to 2.5 years]
Defined as the time from initiation of study intervention until death due to any cause.
- Overall survival (OS) at 12 months [At 12 months]
Defined as the time from initiation of study intervention until death due to any cause.
Eligibility Criteria
Criteria
Core Inclusion Criteria
- Participant has histologically or cytologically documented diagnosis of pancreatic adenocarcinoma with metastatic disease. Participants with locally advanced disease are not eligible.
- Participants with recurrent locally advanced disease are eligible, provided: i. the last dose of chemotherapy and/or radiotherapy occurred > 4 months prior to the first dose of study intervention, and; ii. no systemic or radiotherapy has been administered in the metastatic setting.
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Participant must have measurable disease by RECIST v1.1.
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Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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A baseline tumor tissue sample is mandatory for enrollment. If archival tumor tissue is not available, then a fresh tumor biopsy must be provided.
Core Exclusion Criteria
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Participant must not have received any prior treatment, including chemotherapy, biological therapy, or targeted therapy for mPDAC, with the following exceptions and notes:
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Participants who have received prior neoadjuvant or adjuvant therapy for pancreatic adenocarcinoma are eligible if neoadjuvant and adjuvant therapy (including chemotherapy and/or radiotherapy) was completed more than 4 months before the start of study intervention.
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Prior surgical resection is permitted.
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Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
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Participants with an active, known or suspected autoimmune disease. Participants with: type I diabetes mellitus; hypothyroidism only requiring hormone replacement; a history of Hashimoto syndrome, within 3 years of the first dose of study intervention, which resolved to hypothyroidism alone; skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment; or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, Los Angeles | Los Angeles | California | United States | 90095 |
| 2 | University of California, San Francisco | San Francisco | California | United States | 94143 |
| 3 | Stanford University | Stanford | California | United States | 94305 |
| 4 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 5 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 6 | University of Pennsylvania, Abramson Cancer Center | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Parker Institute for Cancer Immunotherapy
- Bristol-Myers Squibb
- Cancer Research Institute, New York City
Investigators
- Study Director: Parker Institute for Cancer Immunotherapy, Parker Institute for Cancer Immunotherapy
Study Documents (Full-Text)
None provided.More Information
Publications
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