Clinical Trials /

Durvalumab and "Booster" Radiation in Metastatic Adenocarcinoma of the Pancreas

NCT03490760

Description:

This is a single-institution, single-arm phase II trial of Durvalumab combined with Radiation Therapy (RT) for metastatic pancreatic cancer patients who have progressed through first-line chemotherapy.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab and "Booster" Radiation in Metastatic Adenocarcinoma of the Pancreas
  • Official Title: Phase II Trial of In Situ Tumor Vaccination Using Durvalumab and "Booster" Radiation Therapy in Patients With Metastatic Adenocarcinoma of the Pancreas Who Have Progressed Through First-line Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: ESR 15 11078
  • NCT ID: NCT03490760

Conditions

  • Adenocarcinoma of the Pancreas

Interventions

DrugSynonymsArms
DurvalumabDurvalumab plus Radiation Therapy

Purpose

This is a single-institution, single-arm phase II trial of Durvalumab combined with Radiation Therapy (RT) for metastatic pancreatic cancer patients who have progressed through first-line chemotherapy.

Detailed Description

      This is a single-institution phase II trial of Durvalumab combined with Radiation Therapy
      (RT) for metastatic pancreatic cancer patients who have progressed through first-line
      chemotherapy. Pancreatic cancer patients who have received second-line or greater
      chemotherapy in the metastatic setting are not eligible. Target accrual is 39 patients.
      Durvalumab 1500 mg (or 20 mg/m2 if <30 kg) IV every 4 weeks will be started and continued
      during RT and afterwards until the patient experiences either unacceptable toxicity or
      disease progression, whichever comes first. Patients must have at least three
      radiographically measurable pancreatic cancer lesions in different organs that have not
      previously received RT, two of which will receive RT. Eligible lesions include either the
      primary pancreatic tumor in unresected patients or distant metastatic lesions. Three
      fractions of 8 Gy each will be prescribed to one lesion during Week 3. Three fractions of 8
      Gy each will be prescribed to the second lesion during Week 5.

      This is a single-arm trial with continuous monitoring of acute non-hematologic toxicity with
      the primary endpoint of progression free survival. Efficacy will be evaluated by time to
      progression or death, whichever comes first, and compared to historical control of
      chemotherapy alone as reported in the literature.
    

Trial Arms

NameTypeDescriptionInterventions
Durvalumab plus Radiation TherapyExperimentalDurvalumab 1500 mg (or 20 mg/m2 if <30 kg) IV every 4 weeks plus 24 Gy in 3 daily fractions to one lesion during Week 3 and 24 Gy in 3 daily fractions to the second lesion during Week 5.
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Biopsy-proven metastatic pancreatic adenocarcinoma with progression through standard
             first-line chemotherapy. Chemotherapy given as part of prior chemoradiation does not
             count as a line of therapy. Chemotherapy given as part of prior chemoradiation in the
             setting of non-metastatic pancreatic cancer does not count as a line of therapy.

          -  At least 3 radiographically distinct pancreatic cancer lesions that are measurable by
             RECIST 1.1 criteria, including 2 that are eligible for RT.

          -  Lesions that will receive RT are separated by ≥3 cm and none >7 cm in greatest
             dimension.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Life expectancy of ≥12 weeks.

          -  Adequate liver and kidney function.

          -  Adequate blood cell count.

          -  Female subjects must either be of non-reproductive potential or must have a negative
             serum pregnancy test upon study entry.

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study

          -  Previous enrollment in the present study.

          -  Any previous treatment with a programmed cell death 1 or programmed cell death ligand
             1 inhibitor including Durvalumab.

          -  Prior RT to any lesion that would receive RT on this protocol.

          -  Prior RT that could lead to an unacceptably high risk of clinically significant normal
             tissue injury due to high cumulative normal tissue dose as determined by the
             investigator.

          -  Subjects who have received more than 1 line of chemotherapy in the metastatic setting.

          -  History of another primary malignancy except for: 1) malignancy treated with curative
             intent and with no known active disease ≥3 years before the first dose of study drug
             and of low potential risk for recurrence; 2) adequately treated non-melanoma skin
             cancer or lentigo maligna without evidence of disease; 3) adequately treated carcinoma
             in situ without evidence of disease (e.g., cervical cancer in situ).

          -  Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
             endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
             antibodies, other investigational agent) ≤14 days prior to the first dose of study
             drug.

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
             electrocardiograms (ECGs) using Fridericia's Correction.

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of Durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
             systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
             prednisone, or an equivalent corticosteroid.

          -  Any unresolved toxicity (> grade 2, Common Terminology Criteria for Adverse Events
             version 4.03) from previous anti-cancer therapy. Subjects with irreversible toxicity
             that is not reasonably expected to be exacerbated by the investigational product may
             be included (e.g., hearing loss, peripherally neuropathy).

          -  Any prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous
             immunotherapy agent, or any unresolved immune-related adverse event (irAE) >Grade 1.

          -  Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
             with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment (within
             the past 2 years) are not excluded.

          -  Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
             ulcerative colitis)

          -  History of primary immunodeficiency.

          -  History of allogeneic organ transplant.

          -  History of liver cirrhosis and Child-Pugh class B or C.

          -  History of hypersensitivity to Durvalumab or any excipient.
      
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:assessed up to 3 years
Safety Issue:
Description:Time to progression or death, whichever comes first

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Baptist Health South Florida

Trial Keywords

  • Metastatic Adenocarcinoma of the Pancreas

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