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

• ClinicalTrials.gov Identifier: NCT02868632
• Recruitment Status: Withdrawn
• First Posted: August 16, 2016
• Last Update Posted: April 5, 2019
• Sponsor: NYU Langone Health
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): NYU Langone Health

Tracking Information

• First Submitted Date: August 8, 2016
• First Posted Date: August 16, 2016
• Last Update Posted Date: April 5, 2019
• Actual Study Start Date: August 7, 2016
• Actual Primary Completion Date: March 4, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 11, 2016)

Overall Survival [ Time Frame: 24 Months ]

Kaplan Meier curves will be used to summarize Overall Survival.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 11, 2016)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Immune Checkpoint Inhibition With Radiation Therapy in Unresectable, Non-metastatic Pancreatic Cancer
• Official Title: A Phase I Study of Immune Checkpoint Inhibition (Anti-CTLA4 and/or Anti-PD-L1) in Combination With Radiation Therapy in Patients With Unresectable and Non-metastatic Pancreatic Cancer
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Drug: MEDI4736
  anti-PD-L1 human monoclonal antibody
  Other Name: Durvalumab
• Drug: Tremelimumab
  anti-CTLA4 human monoclonal antibody
  Other Name: CP-675,206
• Radiation: Stereotactic Body Radiation Therapy (SBRT)
  Stereotactic body radiation therapy (SBRT) will be administered at the standard dose of 6 Gy daily for 5 days.

Study Arms

• Experimental: Cohort A: MEDI4736 + SBRT
  MEDI4736 10 mg/kg IV every 2 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
  Interventions:

  • Drug: MEDI4736
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)
• Experimental: Cohort B:Tremelimumab + SBRT
  Tremelimumab 10 mg/kg IV every 4 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
  Interventions:

  • Drug: Tremelimumab
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)
• Experimental: Cohort C: MEDI4736 + Tremelimumab + SBRT
  MEDI4736 + Tremelimumab (recommended phase 2 IV dose for combination) plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 16 Subjects
  Interventions:

  • Drug: MEDI4736
  • Drug: Tremelimumab
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: April 3, 2019): 0
• Original Estimated Enrollment (submitted: August 11, 2016): 36
• Actual Study Completion Date: March 4, 2019
• Actual Primary Completion Date: March 4, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion:

• Histopathological confirmation of pancreatic adenocarcinoma prior to study entry.
• Unresectable and non-metastatic disease
• At least 1 measurable metastatic lesion by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques, or as >10 mm with spiral computed tomography (CT) scan, and that is accessible for biopsy.
• Age >18 years
• ECOG performance status 0-1
• Normal organ and marrow function as defined below:

Absolute Neutrophil Count > 1,000/mcL Platelets ≥ 75,000/mcL Total Bilirubin ≤ 2 x ULN Serum Albumin ≥ 2.5 g/dl ALT or AST up to 3 x ULN if no liver metastases or ALT or AST up to 5 x ULN if liver metastases present Creatinine < 2 x institution upper limit of normal OR Creatinine Clearance > 45 mL/min/1.73 m2, as calculated below, for patients with creatinine levels above institutional normal

• No history of another malignancy in the past 5 years, except for treated non-melanoma skin cancer, superficial bladder cancer, or carcinoma-in-situ of the cervix
• No coexisting medical problems that would limit compliance with the study
• Ability to understand and sign a written informed consent document. Patient must have willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
• Female subjects of childbearing potential must have a negative serum pregnancy test prior to study entry
• Female subjects of childbearing potential and males must agree to use a highly effective method of contraception for the duration of study treatment, and for six months after discontinuation of the study drug.

Exclusion:

• Resectable, borderline resectable or metastatic disease
• Prior chemotherapy, targeted therapy, immunotherapy, clinical trials or radiotherapy for pancreatic cancer.
• Active or history of concomitant therapy with any of the following: interleukin (IL) 2, interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies, or chronic use of systemic corticosteroids (inhaled and topical steroids are permitted)
• Active or history of chronic autoimmune disease with symptomatic disease within the 3 years before randomization.
• Active or history of inflammatory bowel disease (colitis, Crohn's disease), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea.
• Diverticulitis within the past 2 years.
• Active HIV infection
• Uncontrolled systemic disease including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Brain metastases
• Patients should not be vaccinated with live attenuated vaccines within 1 month of starting tremelimumab and MEDI4736 treatment.
• History of hypersensitivity reaction to human or mouse antibody products
• Evidence of pre-existing idiopathic pulmonary fibrosis on CT scan at baseline
• Unhealed surgical wound at time of treatment, or history of unhealed surgical wound for more than 30 days
• History of an invasive secondary primary malignancy diagnosed within the previous 3 years, except for appropriately treated stage I endometrial or cervical carcinoma, prostate carcinoma treated surgically or non-melanoma skin cancer.
• Non-protocol antineoplastic agents will not be permitted during this study
• Patients may not recieve other investigational agents.
• Pregnant or lactating women
• Subjects with dementia or significantly altered mental status that would prohibit understanding or rendering of information and consent and compliance with the requirements of the protocol.
• Subjects unable or unwilling to abide by the study protocol or cooperate fully.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02868632
• Other Study ID Numbers: 14-01317
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: NYU Langone Health
• Original Responsible Party: Same as current
• Current Study Sponsor: NYU Langone Health
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

• Principal Investigator: Jennifer Wu, MD; NYU Langone Medical Center

• PRS Account: NYU Langone Health
• Verification Date: April 2019