NCT03767582CompletedPhase 1
A Phase I/II Trial of Combination Immunotherapy With Nivolumab and a CCR2/CCR5 Dual Antagonist (BMS-813160) With or Without GVAX Following Chemotherapy and Radiotherapy for Locally Advanced Pancreatic Ductal Adenocarcinomas (PDACs).
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins2 sites in 1 country22 target enrollmentStarted: December 12, 2019Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 22
- Locations
- 2
- Primary Endpoint
- Number of Participants experiencing study drug-related toxicities
Study Overview
Brief Summary
The purpose of this study is to evaluate if the combination of nivolumab and a CCR2/CCR5 dual antagonist (BMS-813160) with GVAX is safe in patients with locally advanced pancreatic cancer (LAPC) who have received chemotherapy and radiotherapy, and to see if this combination therapy enhances the infiltration of CD8+CD137+ cells in PDACs .
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥18 years.
- •Patients with histologically- or cytologically-proven, surgically unresectable, locally advanced pancreatic adenocarcinoma.
- •If the patient does not have a diagnostic biopsy that is adequate for review at our institution, the patient must agree to a research core biopsy to be performed at Johns Hopkins.
- •If the patient's available imaging is not adequate for review by our institution, the patient must agree to a repeat imaging to be performed at Johns Hopkins.
- •ECOG performance status 0 or 1
- •Life expectancy greater than 3 months.
- •Able to swallow pills or capsules.
- •Patient must have adequate organ function defined by the study-specified laboratory tests.
- •Patients must be eligible to receive FOLFIRINOX-based chemotherapy.
- •Patients must be willing to be treated with stereotactic body radiation therapy (SBRT) only at Johns Hopkins Hospital.
- •Patients must be willing to undergo a core biopsy of the pancreatic cancer.
- •Patients must be willing to undergo a biopsy of the pancreatic cancer if the patient is not deemed a surgical candidate during the pre-surgical evaluation.
- •Must use acceptable form of birth control while on study.
- •Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria
- •Patients cannot have had any prior therapy for the locally advanced pancreatic adenocarcinoma.
- •Have received any anti-neoplastic biologics, vaccines or hormonal treatment, including investigational drugs, within 28 days of the first dose of study.
- •History of past treatment with immunotherapy agents prior to initial enrollment into this study (including, but not limited to: IL-2, interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4 or anti-CCR2/5 drugs).
- •Have had prior organ or tissue allograft or allogeneic bone marrow transplantation, including corneal transplants.
- •Is currently participating or has participated in a study of an investigational agent or using an investigational device for the treatment of cancer.
- •Current use of immunosuppressive medications within 14 days prior to study medications.
- •Have received any vaccine within 14 days prior to study medications.
- •Receiving growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of the first dose of study medication.
- •History of any autoimmune disease. Patients with thyroid disease will be allowed.
- •Has a history of (non-infectious) pneumonitis or current pneumonitis.
- •Has a pulse oximetry < 92% on room air.
- •Requires the use of home oxygen.
- •Patients with uncontrolled intercurrent illness including, but not limited to, myocardial infarction or stroke/transient ischemic attack within the past 6 months, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •12-lead electrocardiogram with QRS ≥ 120 msec, except right bundle branch block ; QTcF (QT corrected for heart rate using Fridericia's method) ≥ 480 msec, except right bundle branch block
- •Has an active infection requiring systemic therapy.
- •Infection with HIV or hepatitis B or C.
- •Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix.
- •Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could impact the absorption of study treatment.
- •Any gastrointestinal surgery that is likely impact upon the absorption of study treatment.
- •Inability to tolerate oral medication.
- •Unable to have blood drawn.
- •Have had surgery within 28 days of the first dose of study medication.
- •Prior use of strong/moderate CYP3A4 inhibitors or inducers within 28 days of the first dose of BMS-
- •Prior use of Class I antiarrhythmics within 28 days of first dose of study medication.
- •Has ascites requiring medical management.
- •Presence of duodenal or gastric invasion by the tumor.
- •Hypersensitivity reaction to any monoclonal antibody.
- •Known allergy or hypersensitivity to study drugs or any of their components of the study arm that participant is enrolling.
- •Woman who are pregnant or breastfeeding.
- •Patient is unwilling or unable to follow the study schedule for any reason.
Arms & Interventions
Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist
Experimental
Intervention: Stereotactic Body Radiation (SBRT) (Radiation)
Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: Stereotactic Body Radiation (SBRT) (Radiation)
Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: Stereotactic Body Radiation (SBRT) (Radiation)
Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: CCR2/CCR5 dual antagonist (Drug)
Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: CCR2/CCR5 dual antagonist (Drug)
Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist
Experimental
Intervention: CCR2/CCR5 dual antagonist (Drug)
Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: GVAX (Drug)
Phase I - GVAX/Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: Nivolumab (Drug)
Phase II - Arm A: Nivolumab/CCR2/CCR5 dual antagonist
Experimental
Intervention: Nivolumab (Drug)
Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist
Experimental
Intervention: Nivolumab (Drug)
Phase II - Arm B: Nivolumab/GVAX/CCR2/CCR5 dual antagonist
Experimental
Intervention: GVAX (Drug)
Outcomes
Primary Outcomes
Number of Participants experiencing study drug-related toxicities
Time Frame: 3 years
Number of participants who experienced study drug-related toxicities as defined by CTCAE v5.0
Percentage of participants treated with immunotherapy who achieve an immune response
Time Frame: 3 years
Percentage of participants who have \>80% increase of infiltration of CD8+CD137+ T cells into the pancreatic ductal adenocarcinoma after treatment with immunotherapy compared to baseline before treatment.
Secondary Outcomes
- Overall survival (OS)(3 years)
- Metastasis free survival (MFS)(3 years)
- Local progression free survival (LPFS) Time(3 years)
- Surgical Resectability Rate(3 years)
- Pathological Response Rate(3 years)
- Change in Quality of life score based on EORTC QLQ-C30/Pan26(Baseline, 3 years)
Investigators
Study Sites (2)
Loading locations...
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