SD-101, Nivolumab, And Radiation Therapy In Treating Patients With Chemotherapy-Refractory Metastatic Pancreatic Cancer

Study Overview

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

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.

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.

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

BIOLOGICAL: Nivolumab
RADIATION: Radiation Therapy
DRUG: TLR9 Agonist SD-101

1452314
NCI-2019-04928 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
UCDCC#281 (OTHER Identifier) (OTHER: University of California Davis Comprehensive Cancer Center)
P30CA093373 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2019-08-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-07-28
First Submitted that Met QC Criteria 2019-08-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-08-01
First Posted (ACTUAL) 2019-08-08	Results First Posted N/A	Last Verified 2023-07

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (SD-101, radiation therapy, nivolumab) Patients 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 o	BIOLOGICAL: Nivolumab Given IV RADIATION: Radiation Therapy Undergo radiation therapy DRUG: TLR9 Agonist SD-101 Given intratumorally

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (SD-101, radiation therapy, nivolumab)

Patients 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 o

BIOLOGICAL: Nivolumab

Given IV

RADIATION: Radiation Therapy

Undergo radiation therapy

DRUG: TLR9 Agonist SD-101

Given intratumorally

Primary Outcome Measures	Measure Description	Time Frame
Incidence of adverse events	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.	Up to 30 days

Secondary Outcome Measures	Measure Description	Time Frame
Disease control rate		Up to 1 year
Duration of response		Up to 1 year
Progression free survival		Up to 1 year
Overall survival		Up to 1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)
Bristol-Myers Squibb
Dynavax Technologies Corporation

Investigators

PRINCIPAL_INVESTIGATOR: Edward J Kim, MD, PhD, University of California, Davis

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record