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.
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
Drug | Synonyms | Arms |
---|
Nivolumab | BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo | Treatment (SD-101, radiation therapy, nivolumab) |
TLR9 Agonist SD-101 | ISS-ODN SD-101, SD-101 | Treatment (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
Name | Type | Description | Interventions |
---|
Treatment (SD-101, radiation therapy, nivolumab) | Experimental | 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 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
June 24, 2021