Clinical Trials /

Safety and Feasibility of PD-1 Blockade in the Treatment of Rectal Cancer

NCT04357587

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.

Related Conditions:
  • Rectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

  • Rectal Neoplasms

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab
CapecitabinePembrolizumab

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

NameTypeDescriptionInterventions
PembrolizumabExperimentalExperimental 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 mg/dL

               -  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

Secondary Outcome Measures

Measure:Treatment response as measured by AJCC tumor regression grade (TRG)
Time Frame:at time of surgical resection, an average of 10 weeks after radiation
Safety Issue:
Description: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 (near complete response): single cells or rare small groups of cancer cells (partial response): residual cancer with evident tumor regression but more than single cells or rare small groups of cancer cells (poor or no response): extensive residual cancer with no evident tumor regression.
Measure:Treatment response as measured by MRI tumor regression grade
Time Frame:4-6 weeks before intervention
Safety Issue:
Description:Treatment response as measured by MRI tumor regression grade. The MRI tumor regression grade uses the following scale: No/minimal fibrosis visible (tiny linear scar) and no tumor signal Dense fibrotic scar (low signal intensity) but no macroscopic tumor signal (indicates no or microscopic tumor) Fibrosis predominates but obvious measurable areas of tumor signal visible Tumor signal predominates with little/minimal fibrosis Tumor signal only: no fibrosis, includes progression of tumor
Measure:Treatment response as measured by Carcinoembryonic antigen (CEA) blood test
Time Frame:4-6 weeks before intervention
Safety Issue:
Description:Treatment response as measured by CEA levels

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Last Updated

April 20, 2020