Overview

Window of Opportunity Study in Colorectal Cancer

Status:
Recruiting
Trial end date:
2022-01-01
Target enrollment:
0
Participant gender:
All
Summary
This is a window of opportunity translational study investigating the use of pre-operative pembrolizumab and chemotherapy or chemoradiotherapy in non-metastatic colorectal cancer.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Centre, Singapore
Collaborator:
Merck Sharp & Dohme Corp.
Treatments:
Capecitabine
Pembrolizumab
Criteria
Inclusion Criteria:

- Adenocarcinoma of the colon (radiologic T4 and/or N2) OR rectal adenocarcinoma with
positive lymph nodes and/or threatened/positive circumferential resection margin
(CRM).

- Patients with rectal adenocarcinoma must have completed neoadjuvant chemoradiation
therapy (or planned to receive neoadjuvant chemoradiation at point of recruitment).

- Male/female participants who are at least 21 years of age on the day of signing
informed consent with histologically confirmed diagnosis of colorectal adenocarcinoma.

- Female participants: A female participant is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions applies: a)
Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the
contraceptive guidance during the treatment period and for at least 120 days after the
last dose of study treatment.

- The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.

- Tumor evaluated to have sufficient tissue for translational studies

- Have provided sufficient archival tumor tissue sample.

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the date of
allocation/randomization.

- Have adequate organ function as defined in the following table. Specimens must be
collected within 10 days prior to the start of study treatment.

Adequate Organ Function Laboratory

1. Absolute neutrophil count (ANC): ≥1500/μL

2. Platelets: ≥100 000/μL

3. Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L

4. Creatinine OR Measured or calculated creatinine clearance: ≤1.5 × Upper 5. Limit of
Normal (ULN) OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional
ULN

5. Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
bilirubin levels >1.5 × ULN

6. Alanine Aminotransferase and Aspartate Aminotransferase: ≤2.5 × ULN

7. Coagulation - International normalized ratio (INR) OR prothrombin time (PT) Activated
partial thromboplastin time (aPTT): ≤1.5 × ULN

Exclusion Criteria:

- A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation of
subject number. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.

- Has any sign of distant metastases or need for emergency surgery.

- Has past history of bowel perforation and abdominal fistula; a recent history of bowel
resection (within past 12 months) and/or patients with radiological evidence of active
bowel obstruction.

- Has intercurrent illness, including but not limited to infections and unstable angina
pectoris.

- Is on anticoagulation therapy (warfarin, low molecular weight heparin, rivaroxaban).

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX-40, and CD137).

- Has received prior systemic anti-cancer therapy including investigational agents
within 1 year prior to allocation, except capecitabine as neoadjuvant therapy for
patients with rectal cancer.

- Has received prior radiotherapy within 1 year of start of study treatment or planned
radiotherapy prior to surgery, except radiotherapy received as neoadjuvant therapy for
patients with rectal cancer.

- Has received a live vaccine within 30 days prior to the first dose of study drug.

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device for cancer within 1 year prior to the
first dose of study treatment.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.

- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years.

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.

- Has an active infection requiring systemic therapy.

- Has Human Immunodeficiency Virus (HIV).

- Has Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known
Hepatitis C virus infection.

- Has a known history of active TB (Bacillus Tuberculosis).

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.