Clinical Trials /

SD-101, Nivolumab, and Radiation Therapy in Treating Patients With Chemotherapy-Refractory Metastatic Pancreatic Cancer

NCT04050085

Description:

This phase I trial studies the side effects of SD-101 when given together with nivolumab and radiation therapy in treating patients with pancreatic cancer that does not respond to treatment with chemotherapy (chemotherapy refractory) and has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as SD-101, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving SD-101, nivolumab, and radiation therapy may work better in treating patients with pancreatic cancer compared to nivolumab or radiation therapy alone.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: SD-101, Nivolumab, and Radiation Therapy in Treating Patients With Chemotherapy-Refractory Metastatic Pancreatic Cancer
  • Official Title: A Pilot Study of Intratumoral SD-101 (Toll-Like Receptor 9 Agonist), Nivolumab, and Radiotherapy for Treatment of Chemotherapy-Refractory Metastatic Pancreatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 1452314
  • SECONDARY ID: NCI-2019-04928
  • SECONDARY ID: UCDCC#281
  • SECONDARY ID: P30CA093373
  • NCT ID: NCT04050085

Conditions

  • Metastatic Pancreatic Adenocarcinoma
  • Refractory Pancreatic Adenocarcinoma
  • Stage IV Pancreatic Cancer AJCC v8

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (SD-101, radiation therapy, nivolumab)
TLR9 Agonist SD-101ISS-ODN SD-101, SD-101Treatment (SD-101, radiation therapy, nivolumab)

Purpose

This phase I trial studies the side effects of SD-101 when given together with nivolumab and radiation therapy in treating patients with pancreatic cancer that does not respond to treatment with chemotherapy (chemotherapy refractory) and has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as SD-101, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving SD-101, nivolumab, and radiation therapy may work better in treating patients with pancreatic cancer compared to nivolumab or radiation therapy alone.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability of intratumoral cytidine-phospho-guanosine
      oligodeoxynucleotide (CpG) in combination with nivolumab and radiotherapy (RT) in
      chemotherapy-refractory metastatic pancreatic adenocarcinoma using Common Terminology
      Criteria for Adverse Events (CTCAE) version (v)5.0 criteria.

      SECONDARY OBJECTIVES:

      I. To obtain preliminary data on disease control rate (DCR), duration of response (DOR),
      progression free survival (PFS), and overall survival (OS) of intratumoral CpG in combination
      with nivolumab and RT in chemotherapy refractory pancreatic adenocarcinoma.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (SD-101, radiation therapy, nivolumab)ExperimentalPatients receive TLR9 agonist SD-101 intratumorally on days 1 and 8 of cycle 1 and day 1 of cycles 2-5. Treatment repeats every 2 weeks for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy on days 1, 3, 5, 8, and 10 of cycle 1. Patients also receive nivolumab IV over 30 minutes on day 2. Cycles with nivolumab repeat every 2 weeks for 24 months in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
  • TLR9 Agonist SD-101

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 - 2

          -  Able and willing to provide written informed consent

          -  Pathology confirmed pancreatic adenocarcinoma by histology or cytology

          -  Life expectancy >= 3 months

          -  Progression during or after greater than or equal to 1 line of systemic treatment for
             metastatic pancreatic adenocarcinoma. Patients who do not tolerate 1st line systemic
             treatment for metastatic pancreatic adenocarcinoma are also eligible

          -  >= 1 metastatic liver lesion amenable for radiation, intratumoral injection, and core
             biopsy

               -  Lesion for radiation, intratumoral injection, and biopsy may not be a previously
                  irradiated lesion but may have been previously treated with liver directed
                  therapy (e.g., radiofrequency ablation [RFA], transarterial chemoembolization
                  [TACE], selective internal radiation therapy [SIRT], etc.) provided there is
                  radiographic evidence of disease progression in the interim since last
                  local/regional treatment

          -  >= 1 target lesion outside the field of radiation, measurable by RECIST v1.1

          -  Absolute neutrophil count (ANC) >= 1000 cells/mm^3

          -  Platelet count >= 50,000/mm^3

          -  Hemoglobin >= 8 g/dL

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 5 times upper
             limit of normal (ULN)

          -  Alkaline phosphatase =< 5 times ULN

          -  Total bilirubin =< 2 times ULN

          -  Creatinine =< 2 times ULN

          -  Patients with hepatitis B virus are allowed if antiviral therapy has been given for >
             8 weeks with viral loads < 100 IU/mL prior to the first dose of trial therapy.
             Subjects with hepatitis C virus are allowed. Viral loads for hepatitis B and C will be
             monitored every 4 weeks for patients with active hepatitis B and/or C

          -  Women with childbearing potential and males must be willing to use adequate birth
             control on trial and until 5 months for women or 7 months for men after the last of
             study therapy

          -  Ability to adhere to study schedule and protocol requirements

          -  Willing to undergo pre-treatment biopsy and on-treatment biopsy

        Exclusion Criteria:

          -  Actively receiving cancer directed, systemic therapy

          -  Prior systemic treatment for pancreatic adenocarcinoma within 2 weeks of first study
             treatment

          -  Known active auto-immune disease or immunodeficiency requiring systemic steroid
             equivalent to prednisone >= 10 mg/day or immunosuppressive therapy within 14 days or 5
             half-lives prior to first dose of trial therapy

          -  History of non-infectious pneumonitis or interstitial lung disease

          -  Active infection requiring systemic therapy defined as ongoing signs/symptoms related
             to the infection without improvement despite appropriate antibiotics, antiviral
             therapy, and/or other treatment

          -  Pregnant or lactating women

          -  Live attenuated vaccine received =< 30 days before first dose of trial therapy

          -  Known history of positive test for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  Contraindications to radiotherapy including but not limited to radiation sensitivity
             syndromes e.g., xeroderma pigmentosum, ataxia telangiectasia

          -  Any significant medical condition including additional active malignancies, laboratory
             abnormalities, or psychiatric illness that would prevent the subject from
             participating and adhering to study related procedures in the view of the principal
             investigator
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days
Safety Issue:
Description:Adverse events, serious adverse events, and clinical laboratory values outside normal limits will be listed for each patient and summarized by body system and dose level in frequency tables. Severity will be graded by Common Terminology Criteria for Adverse Events version 5.0.

Secondary Outcome Measures

Measure:Disease control rate
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Duration of response
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, Davis

Last Updated

February 13, 2020