Study of Immune Checkpoint Inhibition With Radiation Therapy in Unresectable, Non-metastatic Pancreatic Cancer

Phase 1

Withdrawn

• Conditions: Pancreatic Cancer
• Interventions: Drug: MEDI4736; Drug: Tremelimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

• Registration Number: NCT02868632
• Lead Sponsor: NYU Langone Health

Brief Summary

This is an open-label, three-cohort, phase Ib study to determine the safety, recommended phase 2 dose (RP2D), and efficacy of Stereotactic Body Radiation Therapy (SBRT) in combination with either (A) MEDI4736 alone, (B) tremelimumab alone, or (C) the combination of MEDI4736 and tremelimumab for patients with unresectable locally advanced adenocarcinoma of pancreas.

Detailed Description

Patients with unresectable, locally advanced adenocarcinoma of pancreas will receive Stereotactic Body Radiation Therapy (SBRT) at a dose of 6 Gy daily, for 5 days. In Cohort A, where MEDI4736 is given, subjects will receive 10 mg/kg of MEDI4736 every 2 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours). In Cohort B, where tremelimumab is given, subjects will receive 10 mg/kg of tremelimumab every 4 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours). In Cohort C, where MEDI4736 and tremelimumab are given in combination, subjects will receive 10 mg/kg of tremelimumab every 4 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours), followed by 10 mg/kg of MEDI4736 every 4 weeks.

Correlative Studies The investigators will evaluate immune changes in peripheral blood samples and in tumor biopsy fine needle aspirate (FNA) specimens pre- and post- treatment from the 3 cohorts that involve the combination of stereotactic body radiation therapy (SBRT) with either (A) MEDI4736 alone, (B) tremelimumab alone, or (C) the combination of MEDI4736 and tremelimumab. FNA biopsies will be done at baseline (within 30 days of treatment initiation) and Day 28 of cycle 2 (between days 22-28 of cycle 2).

Study Timeline

• Study Start: 2016-08-07
• Study First Submitted: 2016-08-08
• Study First Submitted QC: 2016-08-11
• Study First Posted: 2016-08-16
• Primary Completion: 2019-03-04
• Study Completion: 2019-03-04
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-03
• Last Update Posted: 2019-04-05

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort C: MEDI4736 + Tremelimumab + SBRT	MEDI4736	MEDI4736 + Tremelimumab (recommended phase 2 IV dose for combination) plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 16 Subjects
Cohort B:Tremelimumab + SBRT	Stereotactic Body Radiation Therapy (SBRT)	Tremelimumab 10 mg/kg IV every 4 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
Cohort A: MEDI4736 + SBRT	MEDI4736	MEDI4736 10 mg/kg IV every 2 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
Cohort C: MEDI4736 + Tremelimumab + SBRT	Stereotactic Body Radiation Therapy (SBRT)	MEDI4736 + Tremelimumab (recommended phase 2 IV dose for combination) plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 16 Subjects
Cohort A: MEDI4736 + SBRT	Stereotactic Body Radiation Therapy (SBRT)	MEDI4736 10 mg/kg IV every 2 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
Cohort B:Tremelimumab + SBRT	Tremelimumab	Tremelimumab 10 mg/kg IV every 4 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
Cohort C: MEDI4736 + Tremelimumab + SBRT	Tremelimumab	MEDI4736 + Tremelimumab (recommended phase 2 IV dose for combination) plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 16 Subjects

Primary Outcome Measures

Name	Time	Method
Overall Survival	24 Months	Kaplan Meier curves will be used to summarize Overall Survival.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival	24 Months	Kaplan Meier curves will be used to summarize Progression-Free Survival.
Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	24 Months	Response rates will be estimated with exact 95% confidence intervals for each dose level.
Immune-related Response Criteria (irRC)	24 Hours	Kaplan Meier curves will be used to summarize Clinical Benefit Rate.

Trial Locations

Locations (3)

Georgetown University Medical Center; 🇺🇸 Washington, District of Columbia, United States

New York University School of Medicine; 🇺🇸 New York, New York, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States