Durvalumab and Tremelimumab in Treating Patients With Microsatellite Stable Metastatic Colorectal Cancer to the Liver

NCT03005002 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16423NCI-2016-02001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies the side effects and how well durvalumab and tremelimumab work in treating patients with microsatellite stable colorectal cancer that has spread to the liver. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.

Conditions

Metastatic Carcinoma in the Liver; MLH1 Gene Mutation; MSH6 Gene Mutation; PMS2 Gene Mutation; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Hepatic tumor response as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  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

  Toxicities observed will be summarized in terms of type and severity.

  Up to 1 year

Secondary Outcomes (5)

• Extrahepatic disease response assessed by RECIST 1.1

  Up to 1 year

• Hepatic PFS

  From study treatment to first progression in the treated liver or death (whichever occurs first), assessed up to 1 year

• OS

  From study treatment to death, assessed up to 1 year

• Overall PFS

  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

  Up to 1 year

Other Outcomes (1)

• Tumor immune profiling

  Up to 1 year

Study Arms (1)

Treatment (durvalumab, tremelimumab)

EXPERIMENTAL

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.

Biological: Durvalumab; Other: Laboratory Biomarker Analysis; Biological: Tremelimumab

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (durvalumab, tremelimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (durvalumab, tremelimumab)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Ticilimumab

Treatment (durvalumab, tremelimumab)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

durvalumab; Immunoglobulin G; Disulfides; tremelimumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Marwan Fakih, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2016
• First Posted: December 29, 2016
• Study Start: June 28, 2017
• Primary Completion: November 26, 2019
• Study Completion: November 26, 2019
• Last Updated: December 26, 2019

Record last verified: 2018-12

Locations

US (1)