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

NCT02868632 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 14-01317
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

Pancreatic Cancer

Keywords

Unresectable; Locally Advanced; Non-Metastatic

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Kaplan Meier curves will be used to summarize Overall Survival.

  24 Months

Secondary Outcomes (3)

• Progression-Free Survival

  24 Months

• Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  24 Months

• Immune-related Response Criteria (irRC)

  24 Hours

Study Arms (3)

Cohort A: MEDI4736 + SBRT

EXPERIMENTAL

MEDI4736 10 mg/kg IV every 2 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects

Drug: MEDI4736; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Cohort B:Tremelimumab + SBRT

EXPERIMENTAL

Tremelimumab 10 mg/kg IV every 4 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects

Drug: Tremelimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Cohort C: MEDI4736 + Tremelimumab + SBRT

EXPERIMENTAL

MEDI4736 + Tremelimumab (recommended phase 2 IV dose for combination) plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 16 Subjects

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

Interventions

MEDI4736 DRUG

anti-PD-L1 human monoclonal antibody

Also known as: Durvalumab

Cohort A: MEDI4736 + SBRT; Cohort C: MEDI4736 + Tremelimumab + SBRT

Tremelimumab DRUG

anti-CTLA4 human monoclonal antibody

Also known as: CP-675,206

Cohort B:Tremelimumab + SBRT; Cohort C: MEDI4736 + Tremelimumab + SBRT

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Stereotactic body radiation therapy (SBRT) will be administered at the standard dose of 6 Gy daily for 5 days.

Cohort A: MEDI4736 + SBRT; Cohort B:Tremelimumab + SBRT; Cohort C: MEDI4736 + Tremelimumab + SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• AstraZeneca: collaborator

Study Sites (3)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

durvalumab; tremelimumab; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jennifer Wu, MD

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 16, 2016
• Study Start: August 7, 2016
• Primary Completion: March 4, 2019
• Study Completion: March 4, 2019
• Last Updated: April 5, 2019

Record last verified: 2019-04

Locations

US (3)