- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03005002
Durvalumab and Tremelimumab in Treating Patients With Microsatellite Stable Metastatic Colorectal Cancer to the Liver
A Pilot Feasibility Study of Durvalumab (MEDI4736) and Tremelimumab Following Radioembolization in Patients With Metastatic Microsatellite Stable (MSS) Colorectal Cancer to the Liver
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Establish the safety of durvalumab and tremelimumab following radioembolization with selective internal radiation (SIR)-Spheres in patients with microsatellite stable (MSS) metastatic colorectal cancer to the liver.
II. Determine the hepatic response rate of SIR-Spheres followed by durvalumab and tremelimumab in patients with MSS metastatic colorectal cancer to the liver.
SECONDARY OBJECTIVES:
I. Estimate the progression free survival (PFS) and overall survival (OS) of the overall treated population.
II. Describe the overall response rate of the treated population. III. Describe the extra-hepatic response in the treated population (abscopal responses).
TERTIARY OBJECTIVES:
I. Describe intra-tumor immune alterations following SIR-Spheres, and following durvalumab plus tremelimumab in comparison to baseline through serial hepatic metastases biopsies.
II. Describe the immune alterations in the blood following SIR-Spheres and following durvalumab plus tremelimumab.
OUTLINE:
Patients receive durvalumab intravenously (IV) over 60 minutes and tremelimumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Beginning at week 17, patients receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Duarte, California, United States, 91010
- City of Hope Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Documented informed consent of the subject and/or legally authorized representative
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of > 12 weeks
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (>= 1500 per mm^3)
- Platelet count >= 75 x 10^9/L (>= 75,000 per mm^3)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional upper limit of normal given that all patients have liver metastases
- Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
- Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: >= 60 years old and no menses for >= 1 year without an alternative medical cause; AND/OR history of hysterectomy, AND/OR history of bilateral tubal ligation, AND/OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Patients must have received at least one prior line of therapy for the treatment of metastatic disease with a fluoropyrimidine in combination with oxaliplatin and/or irinotecan; patients with prior adjuvant therapy who progressed within 6 months of completion of treatment may be eligible
- Patients must have liver-only metastases or predominant liver metastatic disease
- Patients should have microsatellite stable (MSS) tumor by polymerase chain reaction (PCR) assay or mismatch repair protein proficient (MMRP) tumor by immunohistochemistry as confirmed by the presence of MLH1, MSH2, MSH6, and PMS2; the diagnosis of colorectal cancer should be confirmed by pathology either on the primary tumor or from a prior biopsy of a metastatic disease site
- Patients should have been identified by their respective physicians as candidates for radioembolization and scheduled to undergo such a procedure
- Patients should agree to serial liver metastases biopsy pre-treatment, post-radioembolization, and post-combination immunotherapy
- Patients should have measurable metastatic disease in the liver, defined (for the purpose of this study) as at least 1 measurable lesion more than 2 cm in size and readily accessible to ultrasound (US) or computed tomography (CT)-guided biopsy
- Patients should not be deemed candidate for curative hepatic resection
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrollment in the present study
- Participation in another clinical study with an investigational product during the last 4 weeks
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease >= 2 years before the first dose of study drug and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligns without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
- Receipt of the last dose of chemotherapy or tyrosine kinase inhibitors should be at least 3 weeks prior to durvalumab and tremelimumab dosing; monoclonal antibodies such as bevacizumab, ziv-aflibercept, ramucirumab, cetuximab, and panitumumab should be at least 6 weeks prior to durvalumab and tremelimumab therapy
- Clinical ascites
- Liver involvement by > 50% with metastatic disease determined by the investigator
- Complete portal vein thrombosis on CT scans
- Failure to satisfy minimum criteria of lung shunting (> 20%) or presence of extrahepatic gastrointestinal activity on microaggregated albumin (MAA) scan or angiogram that preclude SIR-Spheres
- Prior external beam radiation to the liver
- Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's correction
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Any unresolved toxicity (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2) from previous anti-cancer therapy; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
- Any prior systemic anti-cancer immunotherapy treatment
- Active or prior documented autoimmune disease within the past 2 years; NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- History of leptomeningeal carcinomatosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids
- Subjects with uncontrolled seizures
- Patients with symptomatic extrahepatic metastases
- 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 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
- Known allergy or hypersensitivity to investigational product (IP) or any excipient
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (durvalumab, tremelimumab)
Patients receive durvalumab IV over 60 minutes and tremelimumab IV over 60 minutes on day 1.
Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Beginning at week 17, patients receive durvalumab IV over 60 minutes on day 1.
Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hepatic tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame: Up to 1 year
|
Will be summarized using a 90% exact Clopper-Pearson confidence interval
|
Up to 1 year
|
Incidence of adverse events assessed by NCI CTCAE version 4.03
Time Frame: Up to 1 year
|
Toxicities observed will be summarized in terms of type and severity.
|
Up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Extrahepatic disease response assessed by RECIST 1.1
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Hepatic PFS
Time Frame: From study treatment to first progression in the treated liver or death (whichever occurs first), assessed up to 1 year
|
This will be reported for the overall population (safety analysis set) and will be described for liver only (time to hepatic progress or death) and for overall disease burden (progression free survival per se).
Progression free survival will be estimated using the product-limit (Kaplan-Meier) method, with any loss to follow-up as censoring.
|
From study treatment to first progression in the treated liver or death (whichever occurs first), assessed up to 1 year
|
OS
Time Frame: From study treatment to death, assessed up to 1 year
|
Overall survival will be estimated using the product-limit (Kaplan-Meier) method, with any loss to follow-up as censoring.
|
From study treatment to death, assessed up to 1 year
|
Overall PFS
Time Frame: From study treatment to progressive disease (hepatic and extrahepatic) and death, assessed up to 1 year
|
This will be reported for the overall population (safety analysis set) and will be described for liver only (time to hepatic progress or death) and for overall disease burden (progression free survival per se).
Progression free survival will be estimated using the product-limit (Kaplan-Meier) method, with any loss to follow-up as censoring.
|
From study treatment to progressive disease (hepatic and extrahepatic) and death, assessed up to 1 year
|
Overall response rate (both hepatic and extrahepatic disease) assessed by RECIST 1.1
Time Frame: Up to 1 year
|
Up to 1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor immune profiling
Time Frame: Up to 1 year
|
Will be summarized using standard statistical summaries.
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Marwan Fakih, MD, City of Hope Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Immunoglobulins
- Durvalumab
- Tremelimumab
- Antibodies, Monoclonal
- Ipilimumab
- Immunoglobulin G
Other Study ID Numbers
- 16423 (Other Identifier: City of Hope Medical Center)
- NCI-2016-02001 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on MLH1 Gene Mutation
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingBRCA1 Gene Mutation | BRCA2 Gene Mutation | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast Carcinoma | MLH1 Gene Mutation | RAD51C Gene Mutation | RAD51D Gene Mutation | BRIP1 Gene Mutation | PALB2 Gene Mutation | BARD1 Gene Mutation | MSH2 Gene Mutation | MSH6... and other conditionsUnited States
-
Dr Cipto Mangunkusumo General HospitalCompletedColorectal Cancer | APC Gene Mutation | TP53 Gene Mutation | PIK3CA Gene Mutation | KRAS Mutation-Related Tumors | MLH1 Gene MutationIndonesia
-
Memorial Sloan Kettering Cancer CenterRecruitingBRCA1 Mutation | BRCA2 Mutation | APC Gene Mutation | MLH1 Gene Mutation | RAD51C Gene Mutation | RAD51D Gene Mutation | BRIP1 Gene Mutation | PALB2 Gene Mutation | PTEN Gene Mutation | ATM Gene Mutation | CHEK2 Gene Mutation | BARD1 Gene Mutation | MSH2 Gene Mutation | MSH6 Gene Mutation | PMS2 Gene Mutation | POLD1 Gene... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingHereditary Breast and Ovarian Cancer Syndrome | Premenopausal | Deleterious BARD1 Gene Mutation | Deleterious BRCA1 Gene Mutation | Deleterious BRCA2 Gene Mutation | Deleterious BRIP1 Gene Mutation | Deleterious EPCAM Gene Mutation | Deleterious MLH1 Gene Mutation | Deleterious MSH2 Gene Mutation | Deleterious... and other conditionsUnited States
-
Marc Dall'Era, MDNational Cancer Institute (NCI); Janssen, LPRecruitingBRCA1 Gene Mutation | BRCA2 Gene Mutation | Prostate Carcinoma | RAD51C Gene Mutation | BRIP1 Gene Mutation | ATM Gene Mutation | CHEK2 Gene Mutation | NBN Gene Mutation | RAD51 Gene Mutation | CDK12 Gene Mutation | CHEK1 Gene Mutation | DNA Damage Response Gene Mutation | DNA Repair Gene Mutation | FANCA Gene Mutation and other conditionsUnited States
-
Southwest Oncology GroupNational Cancer Institute (NCI)CompletedBRCA1 Gene Mutation | BRCA2 Gene Mutation | Recurrent Squamous Cell Lung Carcinoma | Stage IV Squamous Cell Lung Carcinoma AJCC v7 | BRIP1 Gene Mutation | PALB2 Gene Mutation | ATM Gene Mutation | ATR Gene Mutation | CHEK2 Gene Mutation | NBN Gene Mutation | RAD51 Gene Mutation | CHEK1 Gene Mutation | FANCA Gene... and other conditionsUnited States, Canada
-
Pamela MunsterNational Cancer Institute (NCI)Not yet recruitingBRCA1 Mutation | BRCA2 Mutation | PALB2 Gene Mutation | ATM Gene Mutation | BRCA Mutation | Checkpoint Kinase 2 Gene MutationUnited States
-
Rabin Medical CenterUnknownBRCA1 Gene Mutation | BRCA2 Gene MutationIsrael
-
Sidney Kimmel Comprehensive Cancer Center at Johns...Bristol-Myers Squibb; Vanderbilt University; Avon Breast Health Access FundActive, not recruitingMetastatic Solid Tumor | SF3B1 Gene Mutation | Spliceosome Mutation | U2AF1 Gene Mutation | SRSF2 Gene MutationUnited States
-
Mayo ClinicRecruitingCancer | Cancer Gene Mutation | PAN Gene MutationUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized OsteosarcomaUnited States