Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer
A Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC
4 other identifiers
interventional
110
2 countries
42
Brief Summary
This randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2017
Longer than P75 for phase_2
42 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2016
CompletedFirst Posted
Study publicly available on registry
September 5, 2016
CompletedStudy Start
First participant enrolled
August 14, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2023
CompletedResults Posted
Study results publicly available
June 25, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
January 2, 2027
ExpectedApril 13, 2026
January 1, 2026
6.4 years
August 31, 2016
April 16, 2024
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate
Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. NSCLC: The proportion of patients with response (complete response or partial response according to RECIST) will be compared for each pair-wise comparison of radiotherapy (RT)-containing therapy and control using chi- squared tests. The difference between the proportions responding will be presented with a 90% confidence interval. CRC: The proportion of patients with response will be presented with a 90% exact confidence interval.
Up to 2 years
Secondary Outcomes (6)
Progression-free Survival (PFS)
From date of randomization until objective disease progression or death, whichever occurs first [up to 2 years]
Overall Survival (OS)
From time of randomization to death from any cause [up to 2 years]
Objective Response Per Immune-related Response (irRC) Criteria
Up to 2 years
Incidence of Grade 3-5 Adverse Events
Up to 2 years
Local Control Rate and Abscopal Response Rate
Up to 2 years
- +1 more secondary outcomes
Study Arms (5)
Cohort 1, Arm A (tremelimumab, durvalumab, HD-RT)
EXPERIMENTALPatients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy QD over 10 days for up to 3 fractions.
Cohort 1, Arm B (tremelimumab, Durvalumab, LD-RT)
EXPERIMENTALPatients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours BID on weeks 2, 6, 10 and 14.
Cohort 1, Arm C (tremelimumab, durvalumab)
EXPERIMENTALPatients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.
Cohort 2, Arm A (tremelimumab, durvalumab, HD-RT)
EXPERIMENTALPatients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy QD over 10 days for up to 3 fractions.
Cohort 2, Arm B (tremelimumab, durvalumab, LD-RT)
EXPERIMENTALPatients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours BID on weeks 2, 6, 10 and 14.
Interventions
Given IV
Undergo radiation therapy
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed non-small cell lung cancer (cohort 1) or colorectal cancer (cohort 2)
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1.5 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- Patients in both cohorts must have progressive disease following prior therapy; specifically:
- Cohort 1 (NSCLC): Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy and/or have been deemed not to derive clinical benefit from PD-1 directed treatment; this includes patients who demonstrated an initial response and subsequent progression; no prior treatment with chemotherapy or targeted agents are required; intervening therapy is allowed between previous PD-1 directed treatment and there is no required interval from prior PD-1 treatment required; PD-1 directed treatment includes treatment with antibodies targeting the PD-1 receptor such as pembrolizumab or nivolumab, as well as PD-L1 targeted antibodies such as MEDI4736 (durvalumab), atezolizumab and avelumab; these agents may have been administered as part of a clinical trial
- Cohort 2 (colorectal cancer): Patients must have progressed on \>= one-line chemotherapy
- At least 21 days must have elapsed from prior systemic therapy (chemotherapy or radiation)
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 60%) and life expectancy greater than 6 months; furthermore, enrollment of patients with greater than 10 measurable lesions is discouraged
- Patients must have normal organ and marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening
- Hemoglobin (Hgb) \>= 9 g/dl
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 1.5 x normal institutional limits; this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia \[predominantly unconjugated bilirubin\] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) = \< 2.5 x institutional upper limit of normal; for patients with hepatic metastases, ALT and AST =\< 5 x ULT
- Measured creatinine clearance (CL) \> 40 mL/min OR calculated creatinine clearance (CL) \> 40 mL/min as determined by Cockcroft-Gault (using actual body weight)
- Patients must have at least one lesion that has not previously been irradiated (and is not within a previously radiated field) and for which palliative radiation is potentially indicated and could be safely delivered at the radiation doses specified in this protocol; this lesion must not be the only measurable lesion so that it is still possible to determine the response rate outside of the radiation treatment field; this lesion must not be within the central nervous system (CNS) (brain or spinal cord) or requiring urgent or emergent palliative radiation given the timing of radiation specified on this protocol; furthermore, this lesion:
- +20 more criteria
You may not qualify if:
- Patients who have had systemic (chemotherapy, biologic therapy or radiotherapy) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1)
- Patients who are receiving any other investigational agents
- Patients with untreated brain metastases, spinal cord compression, or leptomeningeal carcinomatosis should be excluded from this clinical trial; patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases; these imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression); in addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of =\< 10 mg/day of prednisone or its equivalent (and anti-convulsants) for at least 14 days prior to the start of treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tremelimumab and MEDI4736 or previous toxicity attributed to MEDI4736 or other PD-1 or PD-L1 directed therapy that led to drug discontinuation
- Prior exposure to immune-mediated therapy, including durvalumab and tremelimumab, except for anti-PD-1 or anti-PD-L1 therapy (including durvalumab) in NSCLC patients; this includes anti-CTLA-4 agents (prior treatment with these agents is NOT allowed in either cohort) and, excludes therapeutic anticancer vaccines, excluding therapeutic anticancer vaccines; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because MEDI4736 (durvalumab), tremelimumab are immune checkpoint inhibitors with the potential for teratogenic or abortifacient effects, as is radiation therapy; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MEDI4736(durvalumab), tremelimumab and radiation, breastfeeding should be discontinued if the mother is treated with MEDI4736(durvalumab), tremelimumab and radiation
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy, whichever is later
- Human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- Any concurrent chemotherapy, immune therapy, biologic, hormonal therapy for cancer treatment
- Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP; the following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (42)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Related Publications (1)
Schoenfeld JD, Giobbie-Hurder A, Ranasinghe S, Kao KZ, Lako A, Tsuji J, Liu Y, Brennick RC, Gentzler RD, Lee C, Hubbard J, Arnold SM, Abbruzzese JL, Jabbour SK, Uboha NV, Stephans KL, Johnson JM, Park H, Villaruz LC, Sharon E, Streicher H, Ahmed MM, Lyon H, Cibuskis C, Lennon N, Jhaveri A, Yang L, Altreuter J, Gunasti L, Weirather JL, Mak RH, Awad MM, Rodig SJ, Chen HX, Wu CJ, Monjazeb AM, Hodi FS. Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2022 Feb;23(2):279-291. doi: 10.1016/S1470-2045(21)00658-6. Epub 2022 Jan 13.
PMID: 35033226DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Anita Giobbie-Hurder, MS (Study biostatistician)
- Organization
- Department of Data Science, Dana-Farber Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Jonathan D Schoenfeld
Dana-Farber - Harvard Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 31, 2016
First Posted
September 5, 2016
Study Start
August 14, 2017
Primary Completion
December 31, 2023
Study Completion (Estimated)
January 2, 2027
Last Updated
April 13, 2026
Results First Posted
June 25, 2024
Record last verified: 2026-01