Study of Durvalumab (MEDI4736) After Chemo-Radiation for Microsatellite Stable Stage II-IV Rectal Cancer
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|ClinicalTrials.gov Identifier: NCT03102047|
Recruitment Status : Recruiting
First Posted : April 5, 2017
Last Update Posted : January 28, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Drug: durvalumab||Phase 2|
The FR-2 study is designed as a phase II, open label, single arm study in patients with microsatellite stable (MSS) stages II-IV rectal cancer, to assess the activity of PD-L1 inhibition with durvalumab (MEDI4736) monotherapy after standard chemo-radiotherapy (chemoRT). The study's primary aim is to determine the safety and efficacy of durvalumab immediately following chemoRT in patients undergoing subsequent surgery with stage II-IV rectal cancer.
One dose of durvalumab will be given every 2 weeks for four total doses beginning within 3-7 days of completing chemoRT. Surgery for all patients must occur within 8-12 weeks of the final dose of RT. Adjuvant chemotherapy after surgical recovery is at the discretion of the treating physician.
During a safety run-in, the first 6 patients will be closely followed for 30 days after last dose of durvalumab without further accrual of patients. Patients will receive durvalumab (750mg IV infusion once every 2 weeks) for 4 total doses. No other concurrent anti-neoplastic medications or treatments aside from standard supportive care will be allowed during the durvalumab treatment phase.
The safety run-in portion of the study will proceed to full enrollment at the proposed study therapy dose, (750 mg IV infusion every 2 weeks), if one or less dose-limiting toxicity (DLT) or significant safety concern attributable to durvalumab is identified during the observation period of the first 6 patients. If there are two or more DLTs, accrual to the study will stop with reassessment of the protocol.
A total of 47 patients will be enrolled in this study for a sample size of 41 surgically evaluable patients.
Required tissue and blood samples will be collected at specific time points and submitted for correlative science studies. Optional tumor and blood samples will be collected from consenting patients upon disease recurrence or progression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study to Assess the Activity of PD-L1 Inhibition With Durvalumab (MEDI4736) After Chemo-Radiotherapy in Patients With Stage II-IV Microsatellite Stable (MSS) Rectal Cancer|
|Actual Study Start Date :||May 14, 2018|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||January 2021|
IV infusion once every 2 weeks for 4 total doses
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)
Other Name: MEDI4736
- Median Neoadjuvant Rectal (NAR) Score [ Time Frame: From the beginning of the study to time of surgical resection, assessed over an estimated 12 weeks ]Compare Median Neoadjuvant Rectal (NAR) Score to historic control using the Wilcoxon test
- Pathologic complete response rate to study therapy [ Time Frame: At the time of surgical resection ]Pathologic Complete response rate ( pCR) (ypT0 and ypN0) of primary rectal cancer and regional nodes determined by pathological examination
- Clinical complete response rate to study therapy [ Time Frame: From one week prior to surgical resection up to time of surgical resection ]Clinical complete response rate cCR (ycT0) determined by the clinical absence of the primary tumor via digital rectal exam and proctoscopic exam
- Rate of negative circumferential margin [ Time Frame: At the time of surgical resection ]Rate of negative circumferential margin in surgical resection specimens
- Sphincter function in patients with sphincter preserving surgery [ Time Frame: From the time of surgical resection to 30 days after surgery ]Sphincter function as determined by number of adverse events related to bowel control
- Severity of post-operative complications [ Time Frame: From time of surgical resection to within 30 days post-operation ]Surgical complications that result in re-hospitalizations or death
- Objective response rate to study therapy [ Time Frame: From date of randomization through study therapy, generally 8-12 weeks ]Objective response rate (ORR) determined by RECIST 1.1 criteria
- Duration of study therapy [ Time Frame: From date study therapy begins to completion of study therapy, generally 8-12 weeks ]Duration of study therapy in selected patients
- Frequency of adverse events assessed by CTCAE 4.0 [ Time Frame: From beginning of study therapy to 90 days after last dose of study therapy ]Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03102047
|Contact: Diana Gosik, RN, BSfirstname.lastname@example.org|
|Principal Investigator:||Norman Wolmark, MD||NSABP Foundation Inc|