Description:
Colorectal cancer is the third most common cancer worldwide and the second leading cause of
cancer mortality in the United States. The current standard of care (SOC) for locally
advanced rectal cancer includes neoadjuvant chemotherapy and radiation followed by surgery.
However, great variability exists in patient's response to neoadjuvant chemoradiotherapy with
only about 20-25% of patients achieving a complete response while other patients achieve a
partial or no treatment response. The purpose of this study is to test the investigational
agent, Pembrolizumab, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil)
in treatment of patients with mismatch repair deficient locally advanced rectal cancer.
Title
- Brief Title: Safety and Feasibility of PD-1 Blockade in the Treatment of Rectal Cancer
- Official Title: Neoadjuvant Immunotherapy in Rectal Cancer: A Pilot Study Examining the Safety and Feasibility of PD-1 Blockade in the Treatment of Rectal Cancer
Clinical Trial IDs
- ORG STUDY ID:
CASE1220
- NCT ID:
NCT04357587
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Pembrolizumab | | Pembrolizumab |
| Capecitabine | | Pembrolizumab |
Purpose
Colorectal cancer is the third most common cancer worldwide and the second leading cause of
cancer mortality in the United States. The current standard of care (SOC) for locally
advanced rectal cancer includes neoadjuvant chemotherapy and radiation followed by surgery.
However, great variability exists in patient's response to neoadjuvant chemoradiotherapy with
only about 20-25% of patients achieving a complete response while other patients achieve a
partial or no treatment response. The purpose of this study is to test the investigational
agent, Pembrolizumab, in combination with SOC radiation and Capecitabine (or 5-Fluorouacil)
in treatment of patients with mismatch repair deficient locally advanced rectal cancer.
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pembrolizumab | Experimental | Experimental pembrolizumab and SOC external beam radiation and capecitabine | - Pembrolizumab
- Capecitabine
|
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 Issue: | |
| Description: | Safety endpoint will be defined by rate of AEs as defined by the CTCAE v5.0 |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Case Comprehensive Cancer Center |
Last Updated
February 26, 2021
