Immune Checkpoint Inhibition (Tremelimumab and/or MEDI4736) in Combination With Radiation Therapy in Patients With Unresectable Pancreatic Cancer

NCT02311361 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 15002715-C-0027
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Stereotactic body radiation therapy (SBRT) is used to treat cancer. It is a way of giving very focused beams of radiation to tumors. Researchers think that the drugs being used in this study might work better when combined with SBRT in people with pancreatic cancer. Objective: \- To study the safety and effectiveness of Durvalumab (MEDI4736) and/or tremelimumab with SBRT. Eligibility: \- People 18 and older who have pancreatic cancer that has not responded or to chemotherapy. They must be candidates for radiation but not resection. Design:

• Participants will be screened with medical history and physical exam. They will have blood tests. Their tumor will be measured using computerized tomography (CT) or magnetic resonance imaging (MRI).
• Participants will have their tumor biopsied with a needle. They will have also have a biopsy after cycle 1.
• Participants will get 1 or 2 drugs in combination with the SBRT.
• For MEDI4736, the duration of each cycle will be 28-days. Participants will get the drug through an intravenous (IV) infusion twice in each cycle (Days 1 and 15).
• For tremelimumab, the duration of the first 6 cycles will each last 28 days. Then the duration of the last 3 cycles will change to 12 weeks. Participants will get the drug through an IV once in each cycle.
• All participants will have SBRT. Some will get 1 dose of radiation and some will get 5. CT scans will map their tumor.
• Participants will have medical history, physical exam, and blood tests in each cycle. They will have a CT scan or MRI every 8 weeks. Cycles will continue for up to 12 months.
• Participants will be contacted yearly for follow-up.

Conditions

Pancreatic Neoplasms; Pancreatic Cancer; Cancer of Pancreas; Cancer of the Pancreas; Pancreas Cancer

Keywords

Anti-PDL1; Anti-CTLA4; Streostatic Body Radiation Therapy (SBRT); Monoclonal Antibody; Antitumor Immunity

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events in Each Cohort With Grade 1 Through 5 Related to Study Drug

  Adverse Events (AEs) are reported by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1=Mild, Grade 2= Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Fatal.

  Participants were assessed from the start of study treatment at Cycle 1 then after every cycle (1 cycle = 28 days) of protocol treatment until 30 days after they were taken off treatment, approximately 4.0 months.

Secondary Outcomes (6)

• Plasma Pharmacokinetic (PK)

  30 days after treatment

• Percentage of Participants With 6-month Overall Survival

  6 month

• Overall Survival

  From study entry to death or date of last contact, whichever occurs first, up to 2 years of follow-up

• Tumor Response Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Measured by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI)

  At screening then every 8 weeks until disease progression or patient is taken off the trial, whichever comes first, approximately 6 months.

• Progression Free Survival (PFS)

  From study entry to disease progression, death or date of last contact, whichever occurs first, an average of 6 months

Study Arms (6)

Durvalumab + 8 Gray (Gy) in 1 fraction

EXPERIMENTAL

Cohort 1/Dose Level A1 Durvalumab + 8 Gray (Gy) in 1 fraction

Biological: Durvalumab; Radiation: Sterostatic body radiation therapy (SBRT)

Durvalumab +5 Gy in 5 fractions

EXPERIMENTAL

Cohort 2/Dose Level A2 Durvalumab +5 Gy in 5 fractions

Biological: Durvalumab; Radiation: Sterostatic body radiation therapy (SBRT)

Tremelimumab + 8 Gy in 1 fraction

EXPERIMENTAL

Cohort 3/Dose Level B1 (was removed with Amendment A) Tremelimumab + 8 Gy in 1 fraction

Biological: Tremelimumab; Radiation: Sterostatic body radiation therapy (SBRT)

Tremelimumab + 5 Gy in 5 fractions

EXPERIMENTAL

Cohort 4/Dose Level B2 (was removed with Amendment A) Tremelimumab + 5 Gy in 5 fractions

Biological: Tremelimumab; Radiation: Sterostatic body radiation therapy (SBRT)

Durvalumab +Tremelimumab + 8 Gy in 1 fraction

EXPERIMENTAL

Cohort C/ Dose Level C1 Durvalumab +Tremelimumab + 8 Gy in 1 fraction

Biological: Durvalumab; Biological: Tremelimumab; Radiation: Sterostatic body radiation therapy (SBRT)

Durvalumab +Tremelimumab +5 Gy in 5 fractions

EXPERIMENTAL

Cohort C/Dose Level C2 Durvalumab +Tremelimumab +5 Gy in 5 fractions

Biological: Durvalumab; Biological: Tremelimumab; Radiation: Sterostatic body radiation therapy (SBRT)

Interventions

Durvalumab BIOLOGICAL

10 mg/kg, mg intravenous (IV), every two weeks, or 1500 mg, IV, every four weeks.

Also known as: MEDI4736

Durvalumab + 8 Gray (Gy) in 1 fraction; Durvalumab +5 Gy in 5 fractions; Durvalumab +Tremelimumab + 8 Gy in 1 fraction; Durvalumab +Tremelimumab +5 Gy in 5 fractions

Tremelimumab BIOLOGICAL

75 mg IV, every 4 weeks for 16 weeks

Also known as: Ticilmumab

Durvalumab +Tremelimumab + 8 Gy in 1 fraction; Durvalumab +Tremelimumab +5 Gy in 5 fractions; Tremelimumab + 5 Gy in 5 fractions; Tremelimumab + 8 Gy in 1 fraction

Sterostatic body radiation therapy (SBRT) RADIATION

8 Gray (Gy) x 1; 5Gy x 5

Also known as: Sterostatic ablative radiotherapy

Durvalumab + 8 Gray (Gy) in 1 fraction; Durvalumab +5 Gy in 5 fractions; Durvalumab +Tremelimumab + 8 Gy in 1 fraction; Durvalumab +Tremelimumab +5 Gy in 5 fractions; Tremelimumab + 5 Gy in 5 fractions; Tremelimumab + 8 Gy in 1 fraction

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histopathological confirmation of pancreatic adenocarcinoma prior to entering this study by the Laboratory of Pathology of the National Cancer Institute (NCI) to entering this study by the Laboratory of Pathology of the NCI prior to entering this study
• Patients must have disease that is not amenable to potentially curative resection. Primary in-situ (or locally-recurrent) tumor must be present and, in the opinion of radiation oncology, be amenable to radiation therapy as planned in the protocol. Each case will be discussed at GI tumor board with multidisciplinary team.
• Patients must have at least 1 measurable metastatic lesion by Response Evaluation in Solid Tumors (RECIST) 1.1 criteria.
• There is no limit to the number of prior chemotherapy regimens received. Patients must have received at least one line of prior systemic chemotherapy for advanced unresectable and/or metastatic disease.
• Age greater than or equal to 18 years
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count - \> 1,000/mcL
• Platelets - greater than or equal to 100,000/mcL
• total bilirubin - Bili should be less than or equal to 2 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin less than 3.0 mg/dL)
• serum albumin - greater than or equal 2.5 g/dL
• Patients are eligible with alanine aminotransferase (ALT) or aspartate aminotransaminase (AST) up to 3 x ULN. (up to 5 x ULN if liver metastases present)
• Creatinine - \< 2X institution upper limit of normal
• creatinine clearance - \>45 mL/min/1.73 m(2), for patients with creatinine levels above institutional normal

You may not qualify if:

• Patients must not have had standard of care chemotherapy, radiotherapy, or major surgery within the last 2 weeks prior to entering the study. Note: Local surgeries for isolated lesions for palliative intent are acceptable. For recent experimental therapies a 28 day period of time must have elapsed before commencing protocol treatment.
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from Durvalumab (MEDI4736) or tremelimumab, or compromise the ability of the subject to give written informed consent.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome; Graves disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Requirement for intermittent use of bronchodilators or local steroid injections
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment
• Diverticulitis (either active or history of) within the past 2 years. Note that diverticulosis is permitted.
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of Information and Consent and compliance with the requirements of the protocol.
• True positive test results for hepatitis A (Immunoglobulin M (IgM) positive). Subjects with a history of hepatitis A with Immunoglobulin G (IgG) blood test are not excluded. True positive test results hepatitis B, or C infection.
• Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegeners granulomatosis.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736 and tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, and topical steroids
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.

  PMID: 17452677 BACKGROUND

• Reyes-Gibby CC, Chan W, Abbruzzese JL, Xiong HQ, Ho L, Evans DB, Varadhachary G, Bhat S, Wolff RA, Crane C. Patterns of self-reported symptoms in pancreatic cancer patients receiving chemoradiation. J Pain Symptom Manage. 2007 Sep;34(3):244-52. doi: 10.1016/j.jpainsymman.2006.11.007. Epub 2007 May 21.

  PMID: 17513082 BACKGROUND

• Moertel CG, Childs DS Jr, Reitemeier RJ, Colby MY Jr, Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969 Oct 25;2(7626):865-7. doi: 10.1016/s0140-6736(69)92326-5. No abstract available.

  PMID: 4186452 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Tim Greten
• Organization: National Cancer Institute

tim.greten@nih.gov

240-760-6114

Study Officials

• Tim F Greten, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 8, 2014
• Study Start: March 25, 2015
• Primary Completion: October 23, 2019
• Study Completion: December 31, 2020
• Last Updated: April 20, 2021
• Results First Posted: July 17, 2020

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)