Chemoimmunotherapy and Radiation in Pancreatic Cancer (CRIT)

Phase I Trial of Chemoimmunotherapy and Hypofractionated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Malignant Neoplasm
• Intervention / Treatment: Drug: Tadalafil; Drug: Gemcitabine; Radiation: Radiation; Procedure: Pancreaticoduodenectomy

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97213
      • Portland Providence Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Immunochemoradiotherapy; 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.

Drug: Tadalafil; One 2.5 mg tablet is self-administered orally by the study participant on a once daily basis.; Other Names: Cialis; Drug: Gemcitabine; Three doses of gemcitabine (1000 mg / m^2)are given over a 21-day cycle. Patients may receive up to 4 cycles.; Other Names: Gemzar; Radiation: Radiation; Patients will receive 3 doses of radiation (8-10 Gy per fraction).; Procedure: Pancreaticoduodenectomy; Surgical resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	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.	135 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Infiltration in pancreaticoduodenectomy tissue	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.	50 Days
Quantification of T cells in peripheral blood pre- and post-treatment	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.	135 Days

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Todd Crocenzi, MD, Providence Health & Services

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: July 2, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Actual): February 1, 2018
• Last Update Submitted That Met QC Criteria: January 31, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Surgery; Immunotherapy; Pancreas; Chemotherapy; Pancreatic cancer; Pancreaticoduodenectomy; Radiation
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Anti-Infective Agents; Urological Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Gemcitabine; Tadalafil
• Other Study ID Numbers: 13-026A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO