Evaluate the Efficacy of MEDI4736 in Immunological Subsets of Advanced Colorectal Cancer

NCT02227667 | Completed Phase 2 Results

• 1 other identifier: 14-109
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, MEDI4736 has on the patient and cancer. MEDI4736 is a type of medication called an antibody. Antibodies are normal proteins in the body that help fight infections and possibly cancer. MEDI4736 is a special type of an antibody produced in a laboratory. MEDI4736 works by blocking a specific protein called the Programmed Death Ligand-1 (PDL-1), located on tumor cells.

Conditions

Advanced Colorectal Cancer

Keywords

MEDI4736; 14-109

Outcome Measures

Primary Outcomes (1)

• Best Response Rate

  according to RECIST 1.1.

  2 years

Secondary Outcomes (1)

• Number of Participants Evaluated for Toxicities to Determine Safety

  2 years

Study Arms (1)

Patients with Advanced Colorectal Cancer

EXPERIMENTAL

This will be a Simon two-stage design, single arm, phase II study. All subjects will receive MEDI4736 via IV infusion. Subjects will continue treatment for 12 months, or until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur. Following the 12-month treatment period, subjects without evidence for progressive disease or other reason to discontinue treatment will be monitored without further treatment. Upon evidence of PD (with or without confirmation according to RECIST 1.1) during the monitoring period, administration of MEDI4736 may resume at the Q2W schedule, for up to another 12 months. The same treatment guidelines followed during the initial 12-month treatment period will be followed during the retreatment period, including the same dose and frequency of treatments and the same schedule of assessments.

Drug: MEDI4736

Interventions

MEDI4736 DRUG

Patients will be seen the day of administration of MEDI4736. A medical history, with particular reference to toxicities, including medication review, and physical examination will be conducted at each treatment visit.

Patients with Advanced Colorectal Cancer

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained.
• Histologically- or cytologically- confirmed CRC.
• Microsatelite-high colorectal cancer (also known as MSI-H, DNA mismatch repair deficient, or sometimes Lynch syndrome); or increased Tumor-Infiltrating Lymphocytes in an archived tumor specimen or fresh biopsy.
• Locally advanced or metastatic CRC
• Subjects have received two or more standard available therapies known to prolong survival and for which they would be considered eligible. At a minimum, such therapies should include regimens containing oxaliplatin and irinotecan in combination with a fluoropyrimidine (e.g., FOLFOX and FOLFIRI or their variants).
• Age ≥ 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3.
• Platelet count ≥ 90,000/mm3.
• AST and ALT ≤ 3 × institutional upper limit of normal (ULN) or ≤ 5 × ULN for subjects with liver metastases.
• Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN for subjects with documented/suspected Gilbert's disease.
• Serum creatinine ≤ 1.5 x ULN;
• Radiographically measurable disease per RECIST 1.1.
• Life expectancy ≥ 16 weeks.

You may not qualify if:

• Anticancer therapy, monoclonal antibody or major surgery within 4 weeks prior to the first dose of MEDI4736.
• Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
• Any prior Grade ≥ 3 irAE while receiving immunotherapy (including anti-CTLA-4 or anti-CD137 MAb) or any unresolved irAE of any grade (controlled irAE endocrinopathies are allowed).
• Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of intranasal 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 CTCAE \>Grade 2 from previous anti-cancer therapy.
• Active autoimmune disease within the past 2 years, except for mild conditions not requiring systemic treatment, such as vitiligo.
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. NOTE: Local treatment of isolated lesions, excluding target lesions, for palliative intent is acceptable (e.g., by local ablation, surgery or radiotherapy).
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, irritable bowel syndrome, ulcerative colitis).
• Receipt of radiation therapy within 4 weeks prior to starting investigational product, or limited field of radiation for palliation within 2 weeks of the first dose of investigational product.
• Known allergy or reaction to any component of the MEDI4736 formulation or its excipients.
• Known central nervous system (CNS) metastases requiring treatment, such as surgery, radiation or steroids.
• Known history of confirmed primary immunodeficiency.
• History of organ transplant requiring therapeutic immunosuppression.
• Other malignancy within 3 years, except for noninvasive malignancies such as cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that has/have been surgically cured, or prior malignancy considered by the investigator to be of low likelihood for recurrence.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• MedImmune LLC: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

durvalumab

Results Point of Contact

• Title: Dr. Neil Segal, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

segaln@mskcc.org

646-888-4187

Study Officials

• Neil Segal, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: August 28, 2014
• Study Start: December 2, 2014
• Primary Completion: June 29, 2020
• Study Completion: June 29, 2020
• Last Updated: June 18, 2021
• Results First Posted: June 18, 2021

Record last verified: 2021-05

Locations

US (1)