Clinical trial NCT01903083: Chemoimmunotherapy and Radiation in Pancreatic Cancer
Official title: Phase I Trial of Chemoimmunotherapy and Hypofractionated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Malignant Neoplasm
Keywords: Pancreas
Pancreatic cancer
Immunotherapy
Chemotherapy
Radiation
Surgery
Pancreaticoduodenectomy
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2013-07-19
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety
timeFrame: 135 Days
Secondary outcomes:
measure: Immune Infiltration in pancreaticoduodenectomy tissue
timeFrame: 50 Days
measure: Quantification of T cells in peripheral blood pre- and post-treatment
timeFrame: 135 Days
Other outcomes:
Locations:
city: Portland
country: United States
facility: Portland Providence Medical Center
state: Oregon
Study officials:
affiliation: Providence Health & Services
name: Todd Crocenzi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, Solhjem MC, To YY, Greathouse A, Tormoen G, Jutric Z, Young K, Bahjat KS, Gough MJ, Crittenden MR. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016 Aug 16;4:45. doi: 10.1186/s40425-016-0149-6. eCollection 2016.