Clinical trial NCT03767582: Trial of Neoadjuvant and Adjuvant Nivolumab and BMS-813160 With or Without GVAX for Locally Advanced Pancreatic Ductal Adenocarcinomas.
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Locally Advanced Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic Ductal Adenocarcinoma
Keywords: GVAX
Nivolumab
CCR2/CCR5 dual antagonist
Anti-PD-1
Cancer vaccine
Monoclonal antibody
Checkpoint inhibitor
Myeloid modulating agent
Immunotherapy
Neoadjuvant chemotherapy
Stereotactic body radiation therapy
SBRT
Pancreatic cancer
Pancreatic Ductal Adenocarcinoma
PDAC
Locally advanced pancreatic ductal adenocarcinoma
LAPC
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-12-06
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 .


Eligibility criteria: 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.
* Patients cannot have had any prior therapy for the locally advanced pancreatic adenocarcinoma.
* 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:

* Have had non-FOLFIRINOX-based chemotherapy for the pancreatic cancer.
* 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-813160.
* 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.

Primary outcomes:
measure: Number of Participants experiencing study drug-related toxicities
timeFrame: 3 years
measure: Percentage of participants treated with immunotherapy who achieve an immune response
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years
measure: Metastasis free survival (MFS)
timeFrame: 3 years
measure: Local progression free survival (LPFS) Time
timeFrame: 3 years
measure: Surgical Resectability Rate
timeFrame: 3 years
measure: Pathological Response Rate
timeFrame: 3 years
measure: Change in Quality of life score based on EORTC QLQ-C30/Pan26
timeFrame: Baseline, 3 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins Medical Institution
name: Amol Narang, MD
role: PRINCIPAL_INVESTIGATOR
References: