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Rectal CancerPhase 2NCT03102047

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

A Phase 2 study testing durvalumab in people with Rectal Cancer, run by NSABP Foundation Inc at 43 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rectal Cancer
What is being tested?
durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
43 sitesUnited States
Study dates
14 May 2018to 30 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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
  • Unstable angina within 6 months prior to study entry
  • Symptomatic arrhythmia
  • Uncontrolled high blood pressure defined as systolic BP greater than or equal to 150 mmHg or diastolic BP greater than or equal to 100 mmHg with or without anti-hypertensive medication. Patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria.
  • Ongoing or active gastritis or peptic ulcer disease.
  • Active bleeding diatheses which in the opinion of the treating physician poses a significantly increased operative risk.
  • Known history of previous diagnosis of tuberculosis.
  • History of hypersensitivity to durvalumab or any excipient.
  • Known history of active pneumonia, pneumonitis, symptomatic interstitial lung disease, or definitive evidence of interstitial lung disease described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea at rest requiring current continuous oxygen therapy.
  • Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy greater than or equal to 12 months prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements, or interfere with interpretation of study results.
  • Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be performed within 14 days prior to study entry according to institutional standards for women of childbearing potential.)
  • Use of any investigational agent within 4 weeks prior to study entry.

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • University of Michigan Oncology

    Ann Arbor, Michigan, 48109

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Strecker Cancer Center

    Belpre, Ohio, 45714

  • UPMC Hillman Cancer at Upper St Clair

    Bethel Park, Pennsylvania, 15102

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Columbus NCORP

    Columbus, Ohio, 43215

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Doctors Hospital

    Columbus, Ohio, 43228

  • Cancer Care Specialists of Central Illinois

    Decatur, Illinois, 62526

  • Columbus Oncology and Hematology Associates, Inc.

    Delaware, Ohio, 43015

  • Delaware Health Center Grady Cancer Center

    Delaware, Ohio, 43015

  • Cancer Care Specialists of Central Illinois-Crossroads Cancer Center

    Effingham, Illinois, 62401

  • University of Florida

    Gainesville, Florida, 32610

  • UPMC Hillman Cancer Center at Mt. View

    Greensburg, Pennsylvania, 15601

  • Smilow Cancer Hospital Care Center at Guilford

    Guilford, Connecticut, 06437

  • AHN Cancer Institute at Jefferson

    Jefferson Hills, Pennsylvania, 15025

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Marion General Hospital

    Marion, Ohio, 43302

  • The Mark H. Sangmeister Center

    Marion, Ohio, 43302

  • Forbes Regional Hospital

    Monroeville, Pennsylvania, 15146

  • UPMC Hillman Cancer Center at Monroeville

    Monroeville, Pennsylvania, 15146

  • West Virginia University Medicine

    Morgantown, West Virginia, 26506

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • Smilow Cancer Hospital Care Center at Yale

    New Haven, Connecticut, 06510

  • Yale University, Yale Cancer Center

    New Haven, Connecticut, 06520

  • Licking Memorial Hospital

    Newark, Ohio, 43055

  • Smilow Cancer Hospital Care Center at North Haven

    North Haven, Connecticut, 06473

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • WPAON/Medical Center Clinic

    Pittsburgh, Pennsylvania, 15212

  • Western Pennsylvania Hospital dba West Penn Hospital

    Pittsburgh, Pennsylvania, 15224

  • UPCI Hillman/Shadyside

    Pittsburgh, Pennsylvania, 15232

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UPMC Cancer Center at Passavant OHA

    Pittsburgh, Pennsylvania, 15237

  • UPMC Hillman Cancer Center at Passvant HOA

    Pittsburgh, Pennsylvania, 15237

  • Southern Ohio Medical Center

    Port Clinton, Ohio, 45662

  • Cancer Care Specialists of Central Illinois-Swansea

    Swansea, Illinois, 62226

  • Smilow Cancer Hospital Care Center at Trumbull

    Trumbull, Connecticut, 06477

  • UPMC Hillman Cancer Center at Washington

    Washington, Pennsylvania, 15301

  • Smilow Cancer Hospital at Lawrence + Memorial Cancer Center

    Waterford, Connecticut, 06385

  • Wake Forest Baptist Comprehensive Cancer Center

    Winston-Salem, North Carolina, 27157

  • Wake Forest Medical Center

    Winston-Salem, North Carolina, 27157

  • Genesis Health Care Center

    Zanesville, Ohio, 43701

Other trials in United States

About this study

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

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.

Read the detailed description

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 44 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.

Given the increasing use of non-operative therapy for patients with rectal cancer who achieve a complete clinical response and in order to maximize the inclusion of patients participating in this trial, the primary endpoint was changed from NAR score to modified NAR score (mNAR). The mNAR score substitutes values from clinical staging for the pathologic T-Stage and N-Stage for those patients who don't go to surgery because of a complete clinical response and consequently have no pathology. Additionally, because of enrollment challenges related to COVID-19 pandemic and the exploratory nature of including stage IV patients, the stage IV analysis was moved to exploratory and reducing the number of patients needing to be enrolled in the study to approximately 44.

Conditions
Rectal Cancer
Being tested
durvalumab
Keywords
microsatellite stable, MSS, durvalumab, NSABP
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • durvalumabDrug

    Also called MEDI4736

    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)

Study groups in NCT03102047
Study groupRoleWhat they receive
durvalumabExperimentalIV infusion once every 2 weeks for 4 total doses
Receives: Drug: durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median modified Neoadjuvant Rectal (mNAR) Score

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

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

Secondary outcomes (6)

  1. Pathologic complete response rate to study therapy

    Pathologic Complete response rate ( pCR) (ypT0 and ypN0) of primary rectal cancer and regional nodes determined by pathological examination

    Measured: At the time of surgical resection

  2. Clinical complete response rate to study therapy

    Clinical complete response rate cCR (ycT0) determined by the clinical absence of the primary tumor via digital rectal exam and proctoscopic exam

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

  3. Rate of negative circumferential margin

    Rate of negative circumferential margin in surgical resection specimens

    Measured: At the time of surgical resection

  4. Sphincter function in patients with sphincter preserving surgery

    Sphincter function as determined by number of adverse events related to bowel control

    Measured: From the time of surgical resection to 30 days after surgery

  5. Severity of post-operative complications

    Surgical complications that result in re-hospitalizations or death

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

  6. Frequency of adverse events assessed by CTCAE 4.0

    Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0

    Measured: From beginning of study therapy to 90 days after last dose of study therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2017
  2. Study start14 May 2018
  3. Primary completion22 Feb 2021
  4. Study completion30 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03102047
Sponsor's protocol ID
NSABP FR-2
Other IDs
ESR-15-11477
Status last verified
Apr 2022
First submitted
7 Mar 2017
Last updated
20 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing durvalumab in people with Rectal Cancer, run by NSABP Foundation Inc at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median modified Neoadjuvant Rectal (mNAR) Score (time frame: From the beginning of the study to time of surgical resection, assessed over an estimated 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03102047.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2022.

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