Pre-Operative Trial (PGHA vs. PGH) for Resectable Pancreatic Cancer

Phase 2

Terminated

Interventions: Drug: Gemcitabine, Nab-Paclitaxel, hydroxychloroquine and Avelumab
Drug: Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine

Brief Summary: This is a randomized phase II trial that will examine the ability of Avelumab to improve the clinical activity of a pre-operative regimen of gemcitabine, nab-paclitaxel and hydroxychloroquine in subjects with potentially resectable adenocarcinoma of the pancreas.

Detailed Description: This is a phase II, non-blinded, adaptively randomized trial. Patients with PDA are evaluated prior to protocol entry by standard of care testing, including EUS, contrast-enhanced helical abdominal CT scan, or MRI. Patients meeting NCCN criteria for potentially resectable (borderline or resectable) tumors will be eligible. Subjects are randomized to receive either 2 cycles of PGH - gemcitabine and nab-paclitaxel (1000 mg/m2 \& 125 mg/m2, respectively: days 1, 8, and 15) plus oral HCQ (1200 mg PO daily) - or PGH plus Avelumab (PGHA; days 1 and 15 of each 28-day cycle), by means of response-adaptive randomization based on Grade IIB or greater histologic response.

Surgical exploration and pancreatectomy is performed if technically feasible and all toxicities have resolved. HCQ is taken until the evening before surgery. Avelumab is administered every two weeks until up to one week prior to the date of surgery. The Study Coordinator informs subjects of the date of operation. Following successful surgical removal of tumors, patients are then be free to pursue standard of care adjuvant therapy options, at the discretion of their treating physician.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
PGHA	Gemcitabine, Nab-Paclitaxel, hydroxychloroquine and Avelumab	Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine and Avelumab
PGH	Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine	Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine

Primary Outcome Measures

Name	Time	Method
Proportion of Grade IIb or Higher Histolopathologic Responses	up to 3 years	Number of grade IIb+lll+lllm+IV+lVm responses / total number of all grade histolopathologic responses. Histoligic appearance will be assess per the Grading System for Pathological Response: Grade I - Characteristic cytologic changes of malignancy present, but little (\< 10%) or no tumor cell destruction is evident; Grade II - Characteristic cytologic changes of malignancy; 10% to 90% of tumor cells are destroyed; Grade IIa - Destruction of 10% to 50% of tumor cells; Grade IIb - Destruction of 51% to 90% of tumor cells; Grade III - Few (\< 10%) viable-appearing tumor cells are present; Grade IIIm - Sizable pools of mucin present; Grade IV - No viable tumor cells present; Grade IVm - Acellular pools of mucin present.

Secondary Outcome Measures

Name	Time	Method
Change in CA19-9 Levels	Up to 3 years	Levels of CA19-9 (tumor marker) in preoperative and postoperative tissues will be determined. Higher levels of CA19-9 are associated with progressive disease.
Worst Grade of Adverse Event Experienced At Least Probably Related to Treatment	Up to 6 months	Percentage of participants that experienced an adverse event at least probably related to study treatment, by Grade. Adverse events were evaluated per per NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Worst Grade of Adverse Event Experienced At Least Possibly Related to Treatment	Up to 6 months	Percentage of participants that experienced an adverse event at least possibly related to study treatment, by Grade. Adverse events were evaluated per per NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Autophagy Biomarker Levels by Histopathological Response	Up to 3 years	Autophagy biomarker levels in blood by histopathological response (per the Grading System for Pathological Response)
Change in Coagulation Index (CI)	up to 3 years	Comparison of the preoperative and postoperative Thromboelastogram (TEG) Coagulation Index (CI) profile. TEG is an overall assessment of coagulability, quantitatively measures the ability of whole blood to form a clot. Cancer patients are at greater risk for thromboembolism compared to the normal population due to tumor burden and systemic therapies.