Study of Durvalumab (MEDI4736) After Chemo-Radiation for Microsatellite Stable Stage II-IV Rectal Cancer

NCT03102047 | Completed Phase 2 FDA Drug

• 2 other identifiers: NSABP FR-2ESR-15-11477
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 43

Brief Summary

This study is being done to look at the safety and response to the investigational drug durvalumab (MEDI4736) following chemo-radiation therapy for patients with MSS stage II to IV rectal cancer. Durvalumab recognizes specific proteins on the surface of cancer cells and triggers the immune system to destroy the cancer cells. The chemoRT portion of the treatment will be completed just before the course of durvalumab is initiated. In order to learn more about certain characteristics of rectal cancer tumors, this study includes special research tests using samples from diagnostic tumors, a tissue sample from tumors removed during surgery, fresh tumor samples from an area where the cancer has recurred, and blood samples.

Conditions

Rectal Cancer

Keywords

microsatellite stable; MSS; durvalumab; NSABP

Outcome Measures

Primary Outcomes (1)

• Median modified Neoadjuvant Rectal (mNAR) Score

  Compare Median modified Neoadjuvant Rectal (mNAR) Score to historic control using the Wilcoxon test

  From the beginning of the study to time of surgical resection, assessed over an estimated 12 weeks

Secondary Outcomes (6)

• Pathologic complete response rate to study therapy

  At the time of surgical resection

• Clinical complete response rate to study therapy

  From one week prior to surgical resection up to time of surgical resection

• Rate of negative circumferential margin

  At the time of surgical resection

• Sphincter function in patients with sphincter preserving surgery

  From the time of surgical resection to 30 days after surgery

• Severity of post-operative complications

  From time of surgical resection to within 30 days post-operation

Study Arms (1)

durvalumab

EXPERIMENTAL

IV infusion once every 2 weeks for 4 total doses

Drug: durvalumab

Interventions

durvalumab DRUG

Within 3-7 days after completion of chemoradiation, patients will receive durvalumab (750 mg IV infusion) every 2 weeks for 4 doses on Day 1(Dose 1), Day 15 (Dose 2), Day 29 (Dose 3), and Day 43 (Dose 4)

Also known as: MEDI4736

durvalumab

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
• Patients with biopsy-proven adenocarcinoma, stage II- IV rectal cancer.
• The tumor must have been determined to be mismatch repair proficient or microsatellite stable through CLIA approved testing (Immunohistochemistry \[IHC\], polymerase chain reaction \[PCR\], or Next-Generation Sequencing \[NGS\] assays).
• Patients must be candidates for planned surgical resection of their primary rectal cancer 8 - 12 weeks after completion of neoadjuvant chemoRT, even if stage IV.
• Planned neoadjuvant chemoRT treatment must conform to NCCN guidelines.
• Baseline staging prior to chemoRT initiation must be obtained. If stage IV, there must be documentation by PET/CT scan, CT scan, or MRI, that the patient has evidence of measurable distant disease per RECIST 1.1. Note: Patients with stage IV disease should have limited but measurable metastatic disease (one or two organs involved e.g., liver and lung) and primary tumor deemed resectable.
• Blood counts performed within 4 weeks prior to study entry must meet the following criteria:
• ANC must be greater than or equal to 1500/mm3
• Platelet count must be greater than or equal to 75,000/mm3; and
• Hemoglobin must be greater than or equal to 9 g/dL.
• Adequate hepatic function performed within 4 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 Upper limit of normal (ULN) to 3 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
• AST and ALT 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 of study entry, defined as serum creatinine less than or equal to 1.5 x ULN for the lab. (If creatinine is 1.0-1.5 x ULN, the creatinine clearance should be greater than 40 mL/min per Cockcroft-Gault formula (Cockcroft-Gault 1976), or by 24-hour urine collection for determination of creatinine clearance.)
• Patients with reproductive potential (male/female) must agree to use accepted and highly effective methods of contraception while receiving durvalumab, and for at least 3 months after the last dose of durvalumab.

You may not qualify if:

• Diagnosis of anal or small bowel carcinoma.
• Histopathology other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
• Previous therapy with any PD1 or PD-L1 inhibitor (including durvalumab) for any malignancy.
• Completion of pelvic radiotherapy treatment for this current rectal cancer or any prior pelvic radiotherapy (e.g., prior prostate or cervical cancer therapy).
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days after receiving the last dose of durvalumab.
• Acute or chronic hepatitis B or hepatitis C.
• Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency-related (AIDS) illnesses.
• History of brain metastases, uncontrolled spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease.
• Active infection or chronic infection requiring chronic suppressive antibiotics.
• History of allogeneic organ transplantation.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• Active or prior history of autoimmune or inflammatory condition requiring ongoing immunosuppressive medications. This specifically includes use of immunosuppressive medication within 28 days before the first dose of durvalumab with the exceptions of intranasal corticosteroids or systemic corticosteroids at physiological doses, which do not exceed 10mg/day of prednisone or an equivalent corticosteroid.
• Any of the following cardiac conditions:
• Documented NYHA Class III or IV congestive heart failure
• Myocardial infarction within 6 months prior to study entry

Sponsors & Collaborators

• NSABP Foundation Inc: lead

Study Sites (43)

Smilow Cancer Hospital Care Center at Guilford

Guilford, Connecticut, 06437, United States

Location

Smilow Cancer Hospital Care Center at Yale

New Haven, Connecticut, 06510, United States

Location

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Smilow Cancer Hospital Care Center at North Haven

North Haven, Connecticut, 06473, United States

Location

Smilow Cancer Hospital Care Center at Trumbull

Trumbull, Connecticut, 06477, United States

Location

Smilow Cancer Hospital at Lawrence + Memorial Cancer Center

Waterford, Connecticut, 06385, United States

Location

University of Florida

Gainesville, Florida, 32610, 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

University of Michigan Oncology

Ann Arbor, Michigan, 48109, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Wake Forest Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Strecker Cancer Center

Belpre, Ohio, 45714, United States

Location

Adena Regional Medical Center

Chillicothe, Ohio, 45601, United States

Location

Columbus NCORP

Columbus, Ohio, 43215, United States

Location

Grant Medical Center

Columbus, Ohio, 43215, United States

Location

Doctors Hospital

Columbus, Ohio, 43228, United States

Location

Columbus Oncology and Hematology Associates, Inc.

Delaware, Ohio, 43015, United States

Location

Delaware Health Center Grady Cancer Center

Delaware, Ohio, 43015, United States

Location

Marietta Memorial Hospital

Marietta, Ohio, 45750, United States

Location

Marion General Hospital

Marion, Ohio, 43302, United States

Location

The Mark H. Sangmeister Center

Marion, Ohio, 43302, United States

Location

Knox Community Hospital

Mount Vernon, Ohio, 43050, United States

Location

Licking Memorial Hospital

Newark, Ohio, 43055, United States

Location

Southern Ohio Medical Center

Port Clinton, Ohio, 45662, United States

Location

Genesis Health Care Center

Zanesville, Ohio, 43701, United States

Location

UPMC Hillman Cancer at Upper St Clair

Bethel Park, Pennsylvania, 15102, United States

Location

UPMC Hillman Cancer Center at Mt. View

Greensburg, Pennsylvania, 15601, United States

Location

AHN Cancer Institute at Jefferson

Jefferson Hills, Pennsylvania, 15025, United States

Location

Forbes Regional Hospital

Monroeville, Pennsylvania, 15146, United States

Location

UPMC Hillman Cancer Center at Monroeville

Monroeville, Pennsylvania, 15146, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

WPAON/Medical Center Clinic

Pittsburgh, Pennsylvania, 15212, United States

Location

Western Pennsylvania Hospital dba West Penn Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

UPCI Hillman/Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Cancer Center at Passavant OHA

Pittsburgh, Pennsylvania, 15237, United States

Location

UPMC Hillman Cancer Center at Passvant HOA

Pittsburgh, Pennsylvania, 15237, United States

Location

UPMC Hillman Cancer Center at Washington

Washington, Pennsylvania, 15301, United States

Location

West Virginia University Medicine

Morgantown, West Virginia, 26506, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

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: March 7, 2017
• First Posted: April 5, 2017
• Study Start: May 14, 2018
• Primary Completion: February 22, 2021
• Study Completion: December 30, 2021
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

US (43)