Pre-Operative Trial (PGHA vs. PGH) for Resectable Pancreatic Cancer (17-134)
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|ClinicalTrials.gov Identifier: NCT03344172|
Recruitment Status : Terminated (Suspected Serious Adverse Events related to treatment)
First Posted : November 17, 2017
Results First Posted : May 14, 2020
Last Update Posted : May 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer Resectable||Drug: Gemcitabine, Nab-Paclitaxel, hydroxychloroquine and Avelumab Drug: Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase II Trial of Pre-Operative Gemcitabine, Nab-Paclitaxel, and Hydroxychloroquine With or Without Avelumab (PGHA vs. PGH)|
|Actual Study Start Date :||December 13, 2017|
|Actual Primary Completion Date :||April 30, 2019|
|Actual Study Completion Date :||April 30, 2019|
Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine and Avelumab
Drug: Gemcitabine, Nab-Paclitaxel, hydroxychloroquine and Avelumab
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)
Other Name: PGHA
Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine
Drug: Gemcitabine, Nab-Paclitaxel, and hydroxychloroquine
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
Other Name: PGH
- Proportion of Grade IIb or Higher Histolopathologic Responses [ Time Frame: 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.
- Change in CA19-9 Levels [ Time Frame: 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 Possibly Related to Treatment [ Time Frame: 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.
- Worst Grade of Adverse Event Experienced At Least Probably Related to Treatment [ Time Frame: 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.
- Autophagy Biomarker Levels by Histopathological Response [ Time Frame: Up to 3 years ]Autophagy biomarker levels in blood by histopathological response (per the Grading System for Pathological Response)
- Change in Coagulation Index (CI) [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03344172
|United States, Pennsylvania|
|UPMC Hillman Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Nathan Bahary, MD||UPMC Hillman Cancer Center|