Chemoimmunotherapy and Radiation in Pancreatic Cancer

Locally Advanced Malignant Neoplasm Clinical Trial

— CRIT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903083
• Other study ID #: 13-026A
• Status: Completed
• Phase: Phase 1
• First received: July 2, 2013
• Last updated: January 31, 2018
• Start date: July 2013
• Est. completion date: December 2017

Study information

• Verified date: January 2018
• Source: Providence Health & Services
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Locally Advanced Malignant Neoplasm
• Neoplasms

Intervention

Drug:
• Tadalafil
One 2.5 mg tablet is self-administered orally by the study participant on a once daily basis.
• Gemcitabine
Three doses of gemcitabine (1000 mg / m^2)are given over a 21-day cycle. Patients may receive up to 4 cycles.

Radiation:
• Radiation
Patients will receive 3 doses of radiation (8-10 Gy per fraction).

Procedure:
• Pancreaticoduodenectomy
Surgical resection.

Locations

Country	Name	City	State
United States	Portland Providence Medical Center	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Providence Health & Services	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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