Chemoimmunotherapy and Radiation in Pancreatic Cancer

Phase 1

Completed

Interventions: Drug: Tadalafil
Drug: Gemcitabine
Radiation: Radiation
Procedure: Pancreaticoduodenectomy

Brief Summary: The goal of this study is to evaluate the safety of combination treatment that includes chemotherapy, radiation therapy, and immunotherapy in patients with pancreatic cancer.

Detailed Description: This study is for borderline resectable and advanced pancreatic cancer patients. Patients will receive chemotherapy with gemcitabine and immunotherapy with daily tadalafil during the first 21 days of treatment. On study day 22, patients will receive the first of three planned doses of radiation therapy and continue daily tadalafil. Patients are then evaluated to determine if they are candidates for pancreaticoduodenectomy. Patients who are not candidates will continue daily tadalafil and receive gemcitabine chemotherapy. Patients who have surgery will resume daily tadalafil and gemcitabine chemotherapy following recovery from surgery. Patients will receive up to four cycles of gemcitabine.

Recruitment & Eligibility

Inclusion Criteria

Pancreatic adenocarcinoma
Locally advanced unresectable disease, or borderline resectable disease
ECOG (Eastern Cooperative Oncology Group)Performance Status 0 or 1
Ability to provide consent and comply with study protocol
Women of child-bearing potential must have a negative pregnancy test and avoid pregnancy during the study

Exclusion Criteria

Age < 18
History of other malignancy in previous 2 years except carcinoma in situ of the cervix or bladder, or non-melanoma skin cancer
Previous chemotherapy or radiation therapy for pancreatic cancer or previous radiation to the target field
Clinically active autoimmune disease or active infection
History of heart attack within 90 days or stroke within 6 months, hypertension requiring change in blood pressure medications in the last 4 weeks, hypotension, uncontrolled arrhythmias, heart failure (NYHA >= Class 2 in last 6 months), unstable angina, or angina during sexual activity
Use of nitrates or nitroglycerin
History of hereditary degenerative retinal disorders including retinitis pigmentosa
Chronic systemic corticosteroid use at supra-physiologic doses
Use of recreational drugs called 'poppers' like amyl nitrite and butyl nitrite
Blood test results (neutrophils < 1000 /uL (microliter); hemoglobin < 9 gm /dL; platelet count < 1000 cells / uL; significant coagulopathy; significant liver or renal dysfunction

Arm && Interventions

Group	Intervention	Description
Immunochemoradiotherapy	Radiation	Immunotherapy with oral tadalafil daily; three doses of chemotherapy with IV Gemcitabine in 21-day cycles for up to 4 cycles; three fractions of external beam radiation to the pancreas and and regional lymph nodes; pancreaticoduodenectomy (surgical resection) for eligible patients.
Immunochemoradiotherapy	Pancreaticoduodenectomy	Immunotherapy with oral tadalafil daily; three doses of chemotherapy with IV Gemcitabine in 21-day cycles for up to 4 cycles; three fractions of external beam radiation to the pancreas and and regional lymph nodes; pancreaticoduodenectomy (surgical resection) for eligible patients.
Immunochemoradiotherapy	Tadalafil	Immunotherapy with oral tadalafil daily; three doses of chemotherapy with IV Gemcitabine in 21-day cycles for up to 4 cycles; three fractions of external beam radiation to the pancreas and and regional lymph nodes; pancreaticoduodenectomy (surgical resection) for eligible patients.
Immunochemoradiotherapy	Gemcitabine	Immunotherapy with oral tadalafil daily; three doses of chemotherapy with IV Gemcitabine in 21-day cycles for up to 4 cycles; three fractions of external beam radiation to the pancreas and and regional lymph nodes; pancreaticoduodenectomy (surgical resection) for eligible patients.

Primary Outcome Measures

Name	Time	Method
Safety	135 Days	Patients will return be seen in the clinic 8 times over the first 50 days for an evaluation of adverse events and toxicities before being evaluated for surgery. Patients who are not candidates for surgery will be seen in clinic 10 more times over the next 85 days for safety evaluations, and patients who have surgery will be seen 10 times over the 85 days following recovery from surgery for safety evaluations.

Secondary Outcome Measures

Name	Time	Method
Immune Infiltration in pancreaticoduodenectomy tissue	50 Days	For surgery patients, formalin fixed and paraffin-embedded tumor tissue obtained during surgery will be sectioned and immunohistology performed to determine the tumor inflammatory micro-environment and the degree of macrophage and T cell inflammation.
Quantification of T cells in peripheral blood pre- and post-treatment	135 Days	Patients will provide a pre-treatment blood sample and 4 blood samples over 135 days to evaluate the influence of the study treatment on immune parameters. For patients who have surgery, the time period will be longer depending on their recovery time. Post-treatment long term follow up will occur every 12 weeks (+/- 2 weeks) beyond post-recovery date (PRD) 85 for 6 visits. Blood will be collected for immune monitoring at each visit.

Locations (1): Portland Providence Medical Center
🇺🇸
Portland, Oregon, United States