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Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma (REVOLUTION)

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ClinicalTrials.gov Identifier: NCT04787991
Recruitment Status : Not yet recruiting
First Posted : March 9, 2021
Last Update Posted : April 29, 2021
Sponsor:
Collaborators:
Bristol-Myers Squibb
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

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
Metastatic Pancreatic Adenocarcinoma Drug: Nivolumab (Cohort A) Drug: Ipilimumab (Cohort A and B) Drug: Hydroxychloroquine (HCQ) (Cohort B) Drug: Nab-paclitaxel (nP) (Cohort A and B) Drug: Gemcitabine (gem) (Cohort A and B) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, ExploRatory Platform Trial to EValuate ImmunOtherapy Combinations With Chemotherapy for the Treatment of Patients With PreviousLy UnTreated MetastatIc Pancreatic AdenOcarciNoma (REVOLUTION)
Estimated Study Start Date : May 15, 2021
Estimated Primary Completion Date : October 11, 2022
Estimated Study Completion Date : October 11, 2023

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 Name: Opdivo

Drug: Ipilimumab (Cohort A and B)
Ipilimumab will be administered intravenously every 6 weeks for up to 2 cycles.
Other Name: Yervoy

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 Name: Abraxane

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 Name: Gemzar

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 Name: Yervoy

Drug: Hydroxychloroquine (HCQ) (Cohort B)
Hydroxychloroquine will be administered orally daily for up to 2 years.
Other Name: Plaquenil

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 Name: Abraxane

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 Name: Gemzar




Primary Outcome Measures :
  1. Incidence and severity of adverse events [ Time Frame: Up to 2.5 years ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 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.

  2. Disease control rate (DCR) [ Time Frame: At 9 months ]
    Defined as the proportion of participants who achieve confirmed CR or PR or stable disease (SD) lasting at least 16 weeks

  3. Duration of response (DOR) [ Time Frame: 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.

  4. Progression-free survival (PFS) [ Time Frame: 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.

  5. Overall survival (OS) [ Time Frame: Up to 2.5 years ]
    Defined as the time from initiation of study intervention until death due to any cause.

  6. Overall survival (OS) at 12 months [ Time Frame: At 12 months ]
    Defined as the time from initiation of study intervention until 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

Core Inclusion Criteria

  1. Participant has histologically or cytologically documented diagnosis of pancreatic adenocarcinoma with metastatic disease. Participants with locally advanced disease are not eligible.

    a. 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.

  2. Participant must have measurable disease by RECIST v1.1.
  3. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. 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

  1. Participant must not have received any prior treatment, including chemotherapy, biological therapy, or targeted therapy for mPDAC, with the following exceptions and notes:

    1. 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.
    2. Prior surgical resection is permitted.
  2. 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.
  3. 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.

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): NCT04787991


Contacts
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Contact: Please contact the site directly. If there is no contact info, Recruiting sites have contact information. please email revolution0044@parkerici.org

Locations
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United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
Contact: Bindu Cherian    310-633-8400 ext 16048    BCherian@mednet.ucla.edu   
Principal Investigator: Zev Wainberg, MD         
University of California, San Francisco
San Francisco, California, United States, 94143
Contact: Cancer Immunotherapy Trials    877-827-3222    HDFCCC.CIP@ucsf.edu   
Principal Investigator: Andrew Ko, MD         
Stanford University
Stanford, California, United States, 94305
Contact: Gino Pineda    650-725-8474    gpineda@stanford.edu   
Principal Investigator: George Fisher, MD, PhD         
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Contact: Osama Rahma    877-338-7425      
Principal Investigator: Osama Rahma, MD         
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Contact: Amin Yaqubie    646-888-4327    yaqubiea@mskcc.org   
Principal Investigator: Eileen O'Reilly, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Contact: Karen Hoffer       khoffer@pennmedicine.upenn.edu   
Principal Investigator: Mark O'Hara, MD         
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Principal Investigator: Robert Wolff, MD         
Sponsors and Collaborators
Parker Institute for Cancer Immunotherapy
Bristol-Myers Squibb
Cancer Research Institute, New York City
Investigators
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Study Director: Marko Spasic, MD Parker Institute for Cancer Immunotherapy
Publications:
Balachandran VP, Łuksza M, Zhao JN, Makarov V, Moral JA, Remark R, Herbst B, Askan G, Bhanot U, Senbabaoglu Y, Wells DK, Cary CIO, Grbovic-Huezo O, Attiyeh M, Medina B, Zhang J, Loo J, Saglimbeni J, Abu-Akeel M, Zappasodi R, Riaz N, Smoragiewicz M, Kelley ZL, Basturk O; Australian Pancreatic Cancer Genome Initiative; Garvan Institute of Medical Research; Prince of Wales Hospital; Royal North Shore Hospital; University of Glasgow; St Vincent's Hospital; QIMR Berghofer Medical Research Institute; University of Melbourne, Centre for Cancer Research; University of Queensland, Institute for Molecular Bioscience; Bankstown Hospital; Liverpool Hospital; Royal Prince Alfred Hospital, Chris O'Brien Lifehouse; Westmead Hospital; Fremantle Hospital; St John of God Healthcare; Royal Adelaide Hospital; Flinders Medical Centre; Envoi Pathology; Princess Alexandria Hospital; Austin Hospital; Johns Hopkins Medical Institutes; ARC-Net Centre for Applied Research on Cancer, Gönen M, Levine AJ, Allen PJ, Fearon DT, Merad M, Gnjatic S, Iacobuzio-Donahue CA, Wolchok JD, DeMatteo RP, Chan TA, Greenbaum BD, Merghoub T, Leach SD. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017 Nov 23;551(7681):512-516. doi: 10.1038/nature24462. Epub 2017 Nov 8.

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Responsible Party: Parker Institute for Cancer Immunotherapy
ClinicalTrials.gov Identifier: NCT04787991    
Other Study ID Numbers: PICI0044
First Posted: March 9, 2021    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Parker Institute for Cancer Immunotherapy:
Metastatic Pancreatic Adenocarcinoma
Immunotherapy
Platform study
Nivolumab
Ipilimumab
Gemcitabine
nab-paclitaxel
hydroxychloroquine
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Hydroxychloroquine
Paclitaxel
Nivolumab
Ipilimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents