Clinical Trials /

Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy

NCT03404960

Description:

The main purpose of this study is to look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy
  • Official Title: PARPVAX: Parpvax: A Phase 1b/2, Open Label Study of Niraparib Plus Either Ipilimumab or Nivolumab in Patients With Advanced Pancreatic Cancer Whose Disease Has Not Progressed on Platinum-based Therapy

Clinical Trial IDs

  • ORG STUDY ID: 828516
  • NCT ID: NCT03404960

Conditions

  • Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
Niraparib + NivolumabArm A
Niraparib + IpilimumabArm B

Purpose

The main purpose of this study is to look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalNiraparib + Nivolumab
  • Niraparib + Nivolumab
Arm BExperimentalNiraparib + Ipilimumab
  • Niraparib + Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma with
             locally advanced or metastatic disease

          2. Patients must be on treatment with platinum-based (cisplatin, oxaliplatin or
             carboplatin) treatment for locally advanced or metastatic pancreatic cancer and have
             received a minimum of 16 weeks of therapy without evidence of disease progression
             based on the investigator's opinion

          3. Patients may have previously failed non-platinum containing therapy or may never have
             previously progressed on treatment.

             -Discontinuation of the platinum component of the regimen for chemotherapy-related
             toxicity is permissible provided the patient has previously received at least 16 weeks
             of platinum-based therapy without evidence of disease progression ≤8 weeks after
             treatment with the platinum agent

          4. Measurable disease is not required for study entry

          5. Adequate organ function

          6. ECOG performance status of 0-1

        Exclusion Criteria:

          1. Prior treatment with a PARP inhibitor, ipilimumab, nivolumab or other cytotoxic
             T-lymphocyte-associated protein (CTLA-4), PD-1 or PD-L1 inhibitor.

          2. Patients who have demonstrated resistance to platinum agents (e.g. oxaliplatin,
             cisplatin) are not eligible to participate in this study

          3. Clinical evidence of uncontrolled malabsorption and/or any other gastrointestinal
             disorder or defect that would, in the opinion of the investigator, interfere with the
             absorption of niraparib

          4. Received any systemic treatment for pancreatic cancer during the 14 days prior to
             first dose of treatment

          5. Acute infection requiring intravenous antibiotics, antiviral or antifungal agents
             during the 14 days prior to first dose of study therapy.

          6. Expected life expectancy of <12 weeks as determined by the investigator.

          7. Patients will be excluded if they have an active, known or suspected autoimmune
             disease, defined as: patients with a history of inflammatory bowel disease are
             excluded from this study, as are patients with a history of symptomatic autoimmune
             disease (eg rheumatoid arthritis, systemic progressive sclerosis (scleroderma),
             systemic lupus erythematosus, autoimmune vasculitis eg Wegener's Granulomatosis);
             motor neuropathy considered of autoimmune origin (eg Guillian-Barre Syndrome).

             NOTE: Patients are permitted to enroll if they have vitiligo, type I diabetes
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger.

          8. Has a history of interstitial lung disease or active, non-infectious pneumonitis

          9. Has received a live vaccine within 4 weeks prior to the first dose of trial therapy
             (Note: seasonal influenza vaccines for injection are generally inactivated and are
             allowed; however intranasal influenza vaccines (eg. Flu-Mist) are live attenuated
             vaccines and are not allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:6 months after initiation of study therapy
Safety Issue:
Description:Progression-free survival at 6 months (PFS6) for both combinations according to RECIST v1.1, as assessed by the investigator

Secondary Outcome Measures

Measure:Proportion of tumors with homologous recombination deficits (HRD), in patients with stability or response to platinum therapy
Time Frame:Cycle 1 Day 1 through completion of study treatment (maximum 42 months)
Safety Issue:
Description:Identification of HRDs and allele specific LOH via whole exome sequencing
Measure:Objective response rate (ORR) in those with measurable disease
Time Frame:From first restaging assessment through completion of study treatment (maximum 42 months)
Safety Issue:
Description:Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)
Measure:Duration of response (DOR)
Time Frame:From first restaging assessment until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first
Safety Issue:
Description:Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)
Measure:Overall survival (OS)
Time Frame:Cycle 1 Day 1 until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first
Safety Issue:
Description:start of treatment to death due to any cause or last patient contact alive
Measure:Safety and tolerability of this combination. Number of participants with treatment-related adverse events as assessed by CTCAE version 4.03
Time Frame:From the initiation of any study intervention through 100 days (nivolumab patients) or 90 days (all patients) after patient End of Treatment Visit
Safety Issue:
Description:Safety based upon standard laboratory and clinical adverse event monitoring
Measure:Correlation of HRDs with response to treatment with niraparib plus immune checkpoint blockade
Time Frame:Cycle 1 Day 1 through completion of study treatment (maximum 42 months)
Safety Issue:
Description:Identification of HRDs and allele specific LOH via whole exome sequencing
Measure:Immune activation prior to treatment
Time Frame:Prior to initiation of study therapy (maximum 36 months)
Safety Issue:
Description:Assessed using immune biomarkers, and RNAseq of PBMC
Measure:Immune activation prior during treatment
Time Frame:Following receipt of study therapy and through study completion (maximum 42 months)
Safety Issue:
Description:Assessed using immune biomarkers, and RNAseq of PBMC

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pennsylvania

Trial Keywords

  • Platinum
  • chemotherapy
  • Niraparib
  • Ipilimumab
  • Nivolumab
  • Pancreatic adenocarcinoma
  • PARP inhibitor
  • Pancreatic ductal adenocarcinoma
  • DDR
  • PDAC

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