Maintenance Ipilimumab + Nivolumab Post Induction Chemotherapy + SBRT for First Line Treatment Stage IV Pancreatic Cancer

Sponsor
Sheba Medical Center
Study ID
NCT05088889
Phase
PHASE1
Status
Unknown

Conditions

  • Stage IV Pancreatic Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    Nivolumab administered IV over 30 minutes at a dose of 360mg every 3 weeks
  • ipilimumab — DRUG
    Ipilimumab administered IV over 30 minutes at 1 mg/kg every 6 weeks
  • Stereotactic body radiation therapy — RADIATION
    Three fractions of 8 Gy, treated on alternate days
  • Low dose irradiation — RADIATION
    a single fraction of 2Gy will be given to the metastatic lesions at first progression

Study Details

In this study we aim to test the efficacy of a combined and novel approach including induction chemotherapy (per standard of care) followed by SBRT and maintenance ipililumab + nivolumab in the first line setting of stage IV PDAC. Study Hypothesis: Cytotoxic chemotherapy followed by hypofractionated radiotherapy will sensitize pancreatic cancer to immunotherapy consisting of combined PD-1 and CTLA4 blockade. We hypothesize that direct targeting of the pancreatic cancer cells by chemotherapy and hypofractionated radiotherapy is necessary for initial anti-tumor response. Furthermore, the combination of immunotherapy as a maintenance strategy will have profound anti-tumor efficacy in this setting. Implications of hypothesis: * Improved response rate above historical controls * Lengthened progression-free survival * Improved overall-survival Exploratory Hypothesis: We hypothesize that baseline markers of immune activation such as Tumor Infiltrating Lymphocytes and CD8+ lymphocytes will correlate with response to ipililumab + nivolumab and that responders will have distinct tumor immune phenotype as determined by immunohistochemistry and gene expression profiling compared to nonresponders.

Key Dates

Start date
Jan 25, 2022
Status verified
Nov 2023
Primary completion
Jul 1, 2024
Completion
Jul 1, 2024

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: study arm
    Study treatments include SBRT (Stereotactic radiation therapy) to one primary/metastatic tumor (3 fractions of 8Gy) , and ipilimumab (1mg/kg every six weeks) + nivolumab (360mg every three weeks) . Every 8 weeks patients will be assessed for response; responders will continue ipilimumab + nivolumab until disease progression, non-responders will receive very low dose radiation (2Gy single fraction to metastatic lesions of choice) prior to continuing ipilimumab + nivolumab .

Primary Outcome Measure

Objective tumor response rate1 (ORR1) in study patients, assessed by RECIST v1.1 [ Time Frame: From first dose of SBRT until first progression, approximately 36 months. ]

Central Contacts

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