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

NCT03344172 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: HCC# 17-134R01CA181450
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer Resectable

Outcome Measures

Primary Outcomes (1)

• Proportion of Grade IIb or Higher Histolopathologic Responses

  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.

  up to 3 years

Secondary Outcomes (5)

• Change in CA19-9 Levels

  Up to 3 years

• Worst Grade of Adverse Event Experienced At Least Possibly Related to Treatment

  Up to 6 months

• Worst Grade of Adverse Event Experienced At Least Probably Related to Treatment

  Up to 6 months

• Autophagy Biomarker Levels by Histopathological Response

  Up to 3 years

• Change in Coagulation Index (CI)

  up to 3 years

Study Arms (2)

PGHA

EXPERIMENTAL

Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine and Avelumab

Drug: Gemcitabine, Nab-Paclitaxel, hydroxychloroquine and Avelumab

PGH

EXPERIMENTAL

Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine

Drug: Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine

Interventions

Gemcitabine, Nab-Paclitaxel, hydroxychloroquine and Avelumab DRUG

Days 1, 8, 15 of Cycles 1 and 2: gemcitabine (1000mg/m\^2) and nab-paclitaxel (125mg/m\^2) Beginning on Day 8 of Cycle 1: hydroxychloroquine (600mg/BID) daily until day of surgery Day 1 of Cycle 3: avelumab (10mg/kg)

Also known as: PGHA

PGHA

Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine DRUG

Days 1, 8, 15 of Cycles 1 and 2: gemcitabine (1000mg/m\^2) and nab-paclitaxel (125mg/m\^2) Beginning on Day 8 of Cycle 1: hydroxychloroquine (600mg/BID) daily until day of surgery

Also known as: PGH

PGH

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with biopsy-proven adenocarcinoma of the pancreas that is determined to be potentially or borderline resectable by NCCN criteria
• Karnofsky performance status of 70-100%
• No active second malignancy with the exception of basal or squamous cell carcinoma of the skin
• Patient has adequate biological parameters as demonstrated by the following blood counts at screening (obtained ≤14 days prior to randomization)
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
• Platelet count ≥100,000/mm3 (100 × 109/L),
• Hemoglobin (Hgb) ≥9 g/dL. Patient may receive transfusion as needed.
• Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to randomization):
• AST (SGOT), ALT (SGPT) ≤ 2.5 × upper limit of normal range (ULN).
• Total bilirubin ≤ ULN (Except in patients who have Gilbert's Syndrome or patients with recently placed stents for biliary obstruction when bilirubin should be \< 1.5 X ULN).
• Serum Creatinine ≤ 1.5mg/dl OR calculated creatinine clearance ≥ 50 for those patients with creatinine greater than 1.5.
• CPK \< ULN.
• Patients who have an elevated lipase or amylase and no history of autoimmune pancreatitis, nor physical exam concerning for, or CT correlates of pancreatitis can be enrolled. The elevated levels will serve as the new baseline. Changes above that will be termed toxicities as per CTCAE guidelines with relation to the new baseline.
• PT WNL+/- 15 % unless on active anticoagulation.
• PTT WNL+/- 15 % unless on active anticoagulation (suggested to be drawn peripherally to prevent port drawn elevation due to routine heparin flush of ports).

You may not qualify if:

• Subjects deemed surgically unresectable or subjects unwilling to undergo surgical resection
• Prior use of chemotherapy, radiotherapy, and / or investigational agents for pancreatic cancer
• Any evidence of metastasis to distant organs (liver, lung, peritoneum)
• Symptomatic evidence of gastric outlet obstruction
• Inability to adhere to study and/or follow-up procedures
• History of allergic reactions or hypersensitivity to the study drugs (hydroxychloroquine, gemcitabine, nab-Paclitaxel, Avelumab)
• Known or suspected HIV infection
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area.
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids.
• No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan

Sponsors & Collaborators

• Nathan Bahary, MD: lead
• Pfizer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Hydroxychloroquine; avelumab

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Barbara Stadterman, MPH, MCCR; CRS Regulatory Supervisor
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Nathan Bahary, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: associate professor

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: November 17, 2017
• Study Start: December 13, 2017
• Primary Completion: April 30, 2019
• Study Completion: April 30, 2019
• Last Updated: May 14, 2020
• Results First Posted: May 14, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)