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

NCT04787991

Description:

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).

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: PICI0044
  • NCT ID: NCT04787991

Conditions

  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
Nivolumab (Cohort A)OpdivoCohort A: Nivolumab + Ipilimumab + nP/gem
Ipilimumab (Cohort A and B)YervoyCohort A: Nivolumab + Ipilimumab + nP/gem
Hydroxychloroquine (HCQ) (Cohort B)PlaquenilCohort B: Hydroxychloroquine + Ipilimumab + nP/gem
Nab-paclitaxel (nP) (Cohort A and B)AbraxaneCohort A: Nivolumab + Ipilimumab + nP/gem
Gemcitabine (gem) (Cohort A and B)GemzarCohort A: Nivolumab + Ipilimumab + nP/gem

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A: Nivolumab + Ipilimumab + nP/gemExperimental
  • Nivolumab (Cohort A)
  • Ipilimumab (Cohort A and B)
  • Nab-paclitaxel (nP) (Cohort A and B)
  • Gemcitabine (gem) (Cohort A and B)
Cohort B: Hydroxychloroquine + Ipilimumab + nP/gemExperimental
  • Ipilimumab (Cohort A and B)
  • Hydroxychloroquine (HCQ) (Cohort B)
  • Nab-paclitaxel (nP) (Cohort A and B)
  • Gemcitabine (gem) (Cohort A and B)

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events
Time Frame:Up to 2.5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 2.5 years
Safety Issue:
Description: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.
Measure:Disease control rate (DCR)
Time Frame:At 9 months
Safety Issue:
Description:Defined as the proportion of participants who achieve confirmed CR or PR or stable disease (SD) lasting at least 16 weeks
Measure:Duration of response (DOR)
Time Frame:Up to 2.5 years
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Defined as the time from initiation of study intervention to date of first documented radiographic progression of disease or death due to any cause.
Measure:Overall survival (OS)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Defined as the time from initiation of study intervention until death due to any cause.
Measure:Overall survival (OS) at 12 months
Time Frame:At 12 months
Safety Issue:
Description:Defined as the time from initiation of study intervention until death due to any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Parker Institute for Cancer Immunotherapy

Trial Keywords

  • Metastatic Pancreatic Adenocarcinoma
  • Immunotherapy
  • Platform study
  • Nivolumab
  • Ipilimumab
  • Gemcitabine
  • nab-paclitaxel
  • hydroxychloroquine

Last Updated

March 9, 2021