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

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Proportion of Grade IIb or Higher Histolopathologic Responses [up to 3 years]. Number, percentage of participants (95% Confidence Interval). PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=6): 33.3 (4.3 to 77.7); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=8): 50.0 (18.7 to 81.3). Analysis, PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab vs PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine: Odds Ratio (OR) 0.52 (95% CI 0.30 to 6.71); p=0.63; Fisher Exact; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change in CA19-9 Levels [Up to 3 years]. Mean, units per milliliter (U/mL) (95% Confidence Interval). PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=5): -0.37 (-0.87 to 0.13); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=5): -0.88 (-1.54 to -0.22). Analysis, PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab vs PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine: Mean Difference (Final Values) -0.63 (95% CI -1.00 to -0.25); p=0.13; t-test, 2 sided; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Worst Grade of Adverse Event Experienced At Least Possibly Related to Treatment [Up to 6 months]. Number, percetage of participants (95% Confidence Interval). Grade 1: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 6.7 (0.5 to 49.6); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 6.3 (0.5 to 47.8). Grade 2: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 40.0 (12.0 to 76.4); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 18.8 (3.5 to 59.6). Grade 3: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 40.0 (12.0 to 76.4); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 62.5 (26.0 to 88.8). Grade 4: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 6.7 (5.1 to 49.6); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 0.0 (0.0 to 40.9). Grade 5: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 6.7 (5.1 to 49.6); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 6.3 (0.5 to 47.8). No Adverse Events: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 0.0 (0.0 to 52.5); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 6.3 (0.5 to 47.8).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Worst Grade of Adverse Event Experienced At Least Probably Related to Treatment [Up to 6 months]. Number, percentage of participants (95% Confidence Interval). Grade 1: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 13.3 (1.8 to 56.0); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 12.5 (1.7 to 54.0). Grade 2: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 33.3 (8.9 to 71.9); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 18.8 (3.5 to 59.6). Grade 3: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 33.3 (8.9 to 71.9); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 43.3 (14.5 to 78.1). Grade 4: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 0.0 (0.0 to 42.4); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 0.0 (0.0 to 40.9). Grade 5: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 0.0 (0.0 to 42.4); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 0.0 (0.0 to 40.9). No Adverse Events: PGHA: Gemcitabine, Nab-Paclitaxel, Hydroxychloroquine+Avelumab (n=15): 20.0 (3.7 to 61.8); PGH: Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine (n=16): 25.0 (0.6 to 64.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Autophagy Biomarker Levels by Histopathological Response [Up to 3 years].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change in Coagulation Index (CI) [up to 3 years].