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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04787991
Recruitment Status : Recruiting
First Posted : March 9, 2021
Last Update Posted : January 11, 2023
Sponsor:
Collaborators:
Bristol-Myers Squibb
Cancer Research Institute, New York City
Akamis Bio
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy

Tracking Information
First Submitted Date  ICMJE March 4, 2021
First Posted Date  ICMJE March 9, 2021
Last Update Posted Date January 11, 2023
Actual Study Start Date  ICMJE August 9, 2021
Estimated Primary Completion Date October 11, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2021)		 Incidence and severity of adverse events [ Time Frame: Up to 2.5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2021)
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma
Official Title  ICMJE 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)
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Nivolumab (Cohort A)
    Nivolumab will be administered intravenously at 360 mg every 3 weeks for up to 2 years.
    Other Name: Opdivo
  • Drug: Ipilimumab (Cohort A, B and C)
    For Cohort A and B, ipilimumab will be administered intravenously at 1mg/kg every 6 weeks for up to 2 cycles. For Cohort C, ipilimumab will be administered intravenously at 1mg/kg on C2D1 and C4D1.
    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, B and C)
    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, B and C)
    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
  • Drug: NG350A (Cohort C)
    NG-350A will be administered intravenously on Cycle 1 Days 15 (1e12 viral particles), 17 (3e12 viral particles), and 19 (3e12 viral particles).
Study Arms  ICMJE
  • Experimental: Cohort A: Nivolumab + Ipilimumab + nP/gem
    Interventions:
    • Drug: Nivolumab (Cohort A)
    • Drug: Ipilimumab (Cohort A, B and C)
    • Drug: Nab-paclitaxel (nP) (Cohort A, B and C)
    • Drug: Gemcitabine (gem) (Cohort A, B and C)
  • Experimental: Cohort B: Hydroxychloroquine + Ipilimumab + nP/gem
    Interventions:
    • Drug: Ipilimumab (Cohort A, B and C)
    • Drug: Hydroxychloroquine (HCQ) (Cohort B)
    • Drug: Nab-paclitaxel (nP) (Cohort A, B and C)
    • Drug: Gemcitabine (gem) (Cohort A, B and C)
  • Experimental: Cohort C: NG-350A + Ipilimumab + nP/gem
    Interventions:
    • Drug: Ipilimumab (Cohort A, B and C)
    • Drug: Nab-paclitaxel (nP) (Cohort A, B and C)
    • Drug: Gemcitabine (gem) (Cohort A, B and C)
    • Drug: NG350A (Cohort C)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2022)		 45
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2021)		 30
Estimated Study Completion Date  ICMJE January 11, 2024
Estimated Primary Completion Date October 11, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  5. Participant must be age 18 years or older.
  6. Participant must have adequate organ function.

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.
    3. Participants who have received treatment with any other enadenotucirev-based therapy or anti-CD40 antibody at any time are not eligible for the study (cohort C only).
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Please contact the site directly. If there is no contact info, Recruiting sites have contact information. please email rschmidberger@lumabridge.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04787991
Other Study ID Numbers  ICMJE PICI0044
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Parker Institute for Cancer Immunotherapy
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Parker Institute for Cancer Immunotherapy
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Bristol-Myers Squibb
  • Cancer Research Institute, New York City
  • Akamis Bio
Investigators  ICMJE
Study Director: Parker Institute for Cancer Immunotherapy Parker Institute for Cancer Immunotherapy
PRS Account Parker Institute for Cancer Immunotherapy
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP