- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04357587
Safety and Feasibility of PD-1 Blockade in the Treatment of dMMR or MSI-H Rectal Cancer
Neoadjuvant Immunotherapy in Rectal Cancer: A Pilot Study Examining the Safety and Feasibility of PD-1 Blockade in the Treatment of dMMR or MSI-H Rectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study investigates the safety, tolerability, and feasibility of Pembrolizumab, an immunotherapy agent, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil) in treatment of patients with mismatch repair deficient locally advanced rectal cancer. Pembrolizumab is an investigational (experimental) drug that works by enhancing the functional activity of the target lymphocytes (immune cells) to facilitate tumor regression and ultimately immune rejection. Pembrolizumab in combination with radiation and Capcitabine (or 5-Fluorouacil) is experimental because it is not approved by the Food and Drug Administration (FDA) for this specific indication.
The primary objective of this study is to determine the safety, tolerability and feasibility of neoadjuvant pembrolizumab in combination with capectiabine (or 5-Fluorouracil ) in the treatment of patients with MMR-d locally advanced rectal cancer
The secondary objective of this study is to determine the treatment response in MMR-d rectal cancer patients treated with neoadjuvant chemoradiotherapy and Pembrolizumab.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: David Liska, MD
- Phone Number: +1 216-444-9219
- Email: LISKAD@ccf.org
Study Locations
-
-
Ohio
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Cleveland, Ohio, United States, 44122
- Recruiting
- Cleveland Clinic, Case Comprehensive Cancer Center
-
Contact:
- David Liska, MD
- Phone Number: 216-444-9219
- Email: LISKAD@ccf.org
-
Principal Investigator:
- David Liska, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must have confirmed rectal adenocarcinoma Defined as, MRI based clinical stage II (T3-4, N0), stage III (T1-4, N+), or oligometastatic locally advanced stage IV that are candidates for curative surgery
- Tumor location at and/or below the peritoneal reflection on MRI.
- Review and discussion at multidisciplinary tumor board with consensus recommendation for neoadjuvant chemoradiation followed by curative-intent surgery. Documented in EPIC tumor board.
- MMR-deficiency confirmed on immunohistochemistry or MSI status confirmed by PCR.
- ECOG Performance status 0-1
- Life expectancy of ≥ 6 months, in the opinion of and as documented by the treating physician.
Must have normal organ and marrow function as defined below:
- Hemoglobin ≥ 8.0 g/dL
- Leukocytes ≥ 3,000/k/uL
- Absolute neutrophil count ≥ 1,500/k/uL
- Platelet count ≥ 100,000/k/uL
- Total bilirubin ≤ 1.3 x institutional upper limit of normal (ULN)
- AST (SGOT) ≤ 2.5 x institutional upper limit of normal (ULN)
- ALT (SGPT) ≤ 2.5 x institutional upper limit of normal (ULN)
- Must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Prior treatment for rectal cancer or prior radiation for other diagnoses to the expected rectal cancer treatment fields.
- Participants receiving any other investigational agents.
- Unresectable primary tumor or unresectable metastatic disease as determined by imaging.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab or other agents used in this study.
Participants with uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection
- Known history of pneumonitis
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or lactating females.
Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
- Male participants who: Are surgically sterile, OR Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
- HIV-positive participants on combination antiretroviral therapy, participants with active Hepatitis B or C, active tuberculosis, or administration of live vaccine within 30 days of planned start of study therapy will be excluded.
- Participants with a diagnosis of immunodeficiency, active autoimmune disease (including inflammatory bowel disease) or those receiving immunosuppressive therapy within 7 days (other than Prednisone ≤ 5mg daily) prior to the planned start of study treatment will be excluded.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab
Experimental pembrolizumab and SOC external beam radiation and capecitabine
|
200 mg intravenously (IV) on days 1, 22, and 43
Daily fractions of 200 cGy, 5 days a week for the first 5 weeks of the study, excluding weekends
825 mg/m2 orally twice a day on days where radiation therapy is given
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of adverse events (AEs) as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time Frame: 30 days after intervention
|
Safety endpoint will be defined by rate of AEs as defined by the CTCAE v5.0
|
30 days after intervention
|
Proportion of participants able to complete planned neoadjuvant treatment protocol
Time Frame: 45 days after intervention
|
Tolerability as defined by proportion of participants that are able to complete the planned neoadjuvant treatment protocol
|
45 days after intervention
|
Feasibility as defined by proportion of participants with any delay in planned surgery of more than 30 days
Time Frame: 115 days after intervention
|
Feasibility as defined by proportion of participants with any delay in the planned surgery of more than 30 days
|
115 days after intervention
|
Treatment response as measured by AJCC tumor regression grade (TRG)
Time Frame: at time of surgical resection, an average of 10 weeks after radiation
|
Treatment response as measured by pathologic assessment of treatment response using the AJCC TRG following surgical resection. AJCC TRG grading ranges from 0-3: 0 (complete response): no viable cancer cells
|
at time of surgical resection, an average of 10 weeks after radiation
|
Treatment response as measured by MRI tumor regression grade
Time Frame: 4-6 weeks before intervention
|
Treatment response as measured by MRI tumor regression grade. The MRI tumor regression grade uses the following scale:
|
4-6 weeks before intervention
|
Treatment response as measured by Carcinoembryonic antigen (CEA) blood test
Time Frame: 4-6 weeks before intervention
|
Treatment response as measured by CEA levels
|
4-6 weeks before intervention
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: David Liska, MD, Cleveland Clinic, Case Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Rectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Capecitabine
- Pembrolizumab
Other Study ID Numbers
- CASE1220
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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