Study of Durvalumab and Tremelimumab After Radiation for Microsatellite Stable Metastatic Colorectal Cancer Progressing on Chemotherapy

NCT03007407 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: NSABP FC-9ESR-15-11514
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 18

Brief Summary

This study is being done to look at the safety and response to the combination of two investigational drugs, tremelimumab and durvalumab, when given after radiation therapy for patients with microsatellite stable (MSS) metastatic colorectal cancer. Tremelimumab and durvalumab recognize specific proteins on the surface of cancer cells and trigger the immune system to destroy the cancer cells. In order to learn more about certain characteristics of colorectal cancer tumors, this study includes special research tests using samples from diagnostic tumors, fresh tumor samples from an area where the cancer has spread, and blood samples.

Conditions

Colorectal Cancer Metastatic

Keywords

microsatellite stable; MSS; durvalumab; tremelimumab; mCRC; NSABP

Outcome Measures

Primary Outcomes (1)

• Overall Objective Response Rate (ORR) of Dual Immune Checkpoint Blockade by RECIST 1.1

  Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be \<10mm on the short axis. Partial Response (PR): 30% or more decrease in the sum of diameters of target lesions. The reference the baseline sums of diameters. Progressive Disease (PD): 20% or more increase in the sum of diameters of target lesions. The reference is the smallest sum while on study (including the baseline sum if that is the smallest on study). In addition to the relative 20% increase, the sum must also demonstrate an absolute increase 5mm or more. (Note: any appearance of one or more new lesions is also considered progression).Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The reference is the smallest sum of diameters while on study.

  Through treatment, up to 1.3 years

Secondary Outcomes (3)

• Percentage of Patients Who Have Achieved Clinical Benefit

  At 16 weeks

• Median Duration of Response to mCRC (Metastic Colorectal Cancer) Responds to Study Therapy

  Through study completetion (1.3 years)

• Frequency of Adverse Events Assessed by CTCAE 4.0, From Beginning of Treatment to 90 Days After Last Dose

  During treatment (max of 12 cycles; each cycle 28 days) to 90 days after last dose of study therapy

Study Arms (1)

durvalumab and tremelimumab

EXPERIMENTAL

Drug: durvalumab; Drug: Tremelimumab

Interventions

durvalumab DRUG

Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive durvalumab (1500 mg IV infusion) on Day 1 for 4 cycles (in combination with tremelimumab). Beginning with Cycle 5 through Cycle 12, patients will receive durvalumab alone (1500 mg/IV infusion) on Day 1 of each 28 day cycle.

Also known as: MEDI4736

durvalumab and tremelimumab

Tremelimumab DRUG

Following three doses of hypofractionated palliative radiation (Days -2, -1, and Day 0 prior to Cycle 1), patients will receive tremelimumab (75 mg IV infusion) on Day 1 for 4 cycles (in combination with durvalumab).

durvalumab and tremelimumab

Eligibility Criteria

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

You may qualify if:

• The ECOG performance status must be 0 or 1.
• There must be histologic confirmation of a diagnosis of colorectal adenocarcinoma.
• The tumor must have been determined to be microsatellite stable (MSS).
• There must be documentation by positron emission tomography (PET)/computed tomography (CT) scan, CT scan, or magnetic resonance imaging (MRI), that the patient has evidence of measurable metastatic disease per RECIST 1.1.
• Patients must have an accessible metastatic lesion for pretreatment core biopsy.
• Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard metastatic chemotherapy regimens.
• The patient must have multiple sites of metastatic disease with at least one lesion amenable to treatment with stereotactic radiation therapy (SBRT) in the lung or liver and at least one lesion not being irradiated and meeting RECIST 1.1.
• At the time of study entry, blood counts performed within 2 weeks prior to study entry must meet the following criteria:
• ANC (absolute neutrophil count) must be greater than or equal to 1500/mm3,
• Platelet count must be greater than or equal to 100,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL.
• The following criteria for evidence of adequate hepatic function performed within 2 weeks prior to study entry must be met:
• Total bilirubin must be less than or equal to 1.5 x ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation greater than 1.5 x ULN to 3 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
• AST (aspartate aminotransferase)and ALT (alanine transaminase) must be less than or equal to 2.5 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be less than or equal to 5 x ULN.
• Adequate renal function within 4 weeks prior to study entry, defined as serum creatinine less than or equal to 1.5 x ULN for the lab or measured or calculated creatinine clearance greater than 40 mL/min by Cockcroft-Gault formula.

You may not qualify if:

• Diagnosis of anal or small bowel carcinoma.
• Colorectal cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
• Previous therapy with any PD-1 or PD-L1 (programmed cell death-1 (PD-1) protein, programmed death ligand-1 (PDL-1) protein inhibitor including durvalumab or anti-CTLA4 (including tremelimumab) for any malignancy.
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study therapy.
• Active or chronic hepatitis B or hepatitis C.
• Symptomatic or uncontrolled brain metastases requiring concurrent treatments, uncontrolled spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease; uncontrolled seizures.
• Active infection or chronic infection requiring chronic suppressive antibiotics.
• Active or documented inflammatory disease.
• Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency-related (AIDS) illnesses.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of study therapy with the exceptions of intranasal corticosteroids or systemic corticosteroids at physiological doses that do not exceed 10mg/day of prednisone or an equivalent corticosteroid.
• History of allogeneic organ transplantation.
• Any of the following cardiac conditions:
• Documented NYHA (New York Heart Association) Class III or IV congestive heart failure,
• Myocardial infarction within 6 months prior to study entry,
• Unstable angina within 6 months prior to study entry,

Sponsors & Collaborators

• NSABP Foundation Inc: lead

Study Sites (18)

City of Hope

Duarte, California, 91010, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

Smilow Cancer Hospital Care Center at North Haven

North Haven, Connecticut, 06473, United States

Location

UF Health Davis Cancer Pavilion and Shands Med Plaza

Gainesville, Florida, 32608, United States

Location

UF Health Shands Cancer Hospital

Gainesville, Florida, 32608, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Florida Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Centralia Oncology Clinic

Centralia, Illinois, 62801, United States

Location

Cancer Care Specialists of Central Illinois

Decatur, Illinois, 62526, United States

Location

Cancer Care Specialists of Central Illinois/Crossroads Cancer Center

Effingham, Illinois, 62401, United States

Location

Cancer Care Specialists of Central Illinois-Swansea

Swansea, Illinois, 62226, United States

Location

Trinity Health Michigan

Ann Arbor, Michigan, 48106, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

St. Joseph Mercy-Brighton

Brighton, Michigan, 48114, United States

Location

St. Joseph Mercy-Canton

Canton, Michigan, 48188, United States

Location

St Joseph Mercy-Chelsea

Chelsea, Michigan, 48118, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

MeSH Terms

Interventions

durvalumab; tremelimumab

Results Point of Contact

• Title: Director, Department of Site and Study Management
• Organization: NSABP Foundation

industrytrials@nsabp.org

1-800-270-3165

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: January 2, 2017
• Study Start: July 31, 2017
• Primary Completion: April 18, 2019
• Study Completion: August 9, 2019
• Last Updated: December 5, 2022
• Results First Posted: December 5, 2022

Record last verified: 2022-11

Locations

US (18)