Window of Opportunity Study in Colorectal Cancer

NCT03984578 | Completed Phase 2

• 1 other identifier: WoOCRC
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Tumour immune gene expression signature

  Gene expression of key immune genes will be assayed and immune gene expression scores such as IFN-gamma Gene Expression Profile (GEP) signature score (Ayers et al. 2017 JCI) will be compared before (biopsy) and after treatment (surgery).

  From time of first tumour biopsy before treatment to time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment

• Pathology regression

  A change in viable tumour after treatment will be measured by pathologist using tumour regression grade and major pathologic regression.

  From time of first tumour biopsy before treatment to time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment

• Immune T-cell infiltration before and after treatment

  The change in immune cell infiltration will be measured by pathologists through immunohistochemistry and/or immuno-fluorescence.

  From time of first tumour biopsy before treatment to time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment

Secondary Outcomes (3)

• Relative proportion/ percentage of the different immune cell states or immune cell types as inferred from single cell or bulk gene expression profiling

  At time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment

• Relative distribution (percentage) of immune cells with specific expression of lineage markers

  At time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment

• Percentage of cell viability and cell death at fixed time points (e.g. 24 or 48 hours)

  At time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment

Study Arms (3)

Newly Diagnosed Colon cancers

EXPERIMENTAL

Pre-operative CAPEOX 1 cycle Pre-operative Pembrolizumab 2 cycles with cycle 1 on Day 1 (concurrent with start of CAPEOX) and cycle 2 on Day 22.

Drug: CAPEOX; Drug: Pembrolizumab; Procedure: Surgical resection

Newly Diagnosed Rectal Cancers

EXPERIMENTAL

Following completion of neo-adjuvant chemo-radiotherapy, 2 cycles of pre-operative Pembrolizumab administered 3 weeks apart.

Drug: Capecitabine/ 5-FU; Drug: Pembrolizumab; Procedure: Surgical resection

Newly Diagnosed Colon and Rectal Cancers Referred for Pre-Operative Chemotherapy

EXPERIMENTAL

Neoadjuvant pembrolizumab 3-weekly for a maximum of 6 doses to be administered along with XELOX chemotherapy, and additional 1 dose pembrolizumab.

Drug: CAPEOX/Pembrolizumab; Drug: Pembrolizumab alone; Procedure: Surgical resection

Interventions

CAPEOX DRUG

Oral Capecitabine: 1000mg/m2 twice a day from Day 1 to 14 of a 3-week cycle, and IV Oxaliplatin: 130mg/m2 on Day 1

Newly Diagnosed Colon cancers

Pembrolizumab DRUG

IV infusion of 200mg on Day 1 and Day 22

Also known as: Keytruda

Newly Diagnosed Colon cancers

Capecitabine/ 5-FU DRUG

Capecitabine: Oral dose of 825mg/m2/day twice a day on radiation days with concurrent radiation median 50.4 Gy/ 28 fractions; or 5-FU: 225mg/m2/day concurrent with radiation

Newly Diagnosed Rectal Cancers

CAPEOX/Pembrolizumab DRUG

* Oral Capecitabine: 1000mg/m2 twice a day from Day 1 to 14 of a 3-week cycle. * IV Oxaliplatin: 130mg/m2 on Day 1 of a 3-week cycle. * Pembrolizumab: IV infusion of 200mg on Day 1 of a 3-week cycle.

Newly Diagnosed Colon and Rectal Cancers Referred for Pre-Operative Chemotherapy

Pembrolizumab alone DRUG

IV infusion of 200mg 21 days from the last CAPEOX/Pembrolizumab combination dose.

Also known as: Keytruda

Newly Diagnosed Colon and Rectal Cancers Referred for Pre-Operative Chemotherapy

Surgical resection PROCEDURE

Performed after all medical intervention.

Newly Diagnosed Colon and Rectal Cancers Referred for Pre-Operative Chemotherapy; Newly Diagnosed Colon cancers; Newly Diagnosed Rectal Cancers

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For patients with colon cancer (Group 1): Adenocarcinoma of the colon (radiologic T4 and/or N2) OR rectal adenocarcinoma with positive lymph nodes and/or threatened/positive circumferential resection margin (CRM).
• Radiological staging is based on the degree of tumor infiltration beyond the serosa:
• rT1-2 tumors - no tumor extension beyond the serosa.
• rT3 tumors - tumor extension \<5 mm beyond the serosa.
• rT4 tumors - tumor extension ≥5 mm beyond the serosa.
• Lymph nodes are considered positive if they are more than 10 mm in short axis diameter or demonstrate an irregular contour:
• rN0 - absence of nodal involvement.
• rN1 - involvement of 1-3 nodes.
• rN2 - involvement of ≥ 4 nodes.
• For patients with rectal cancer (Group 1): Patients with rectal adenocarcinoma must have completed neoadjuvant chemoradiation therapy (or planned to receive neoadjuvant chemoradiation at point of recruitment).
• Colon or Rectal Cancer patients referred for preoperative chemotherapy (Group 2).
• Note: Patients may be included at any point during the preoperative chemotherapy phase and have pembrolizumab administered concurrently with the remaining cycles of preoperative chemotherapy.
• 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.

You may not qualify if:

• 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, unless medically treated (e.g. by stoma) or deemed to still be suitable for pre-operative systemic therapy; 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.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• 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. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• 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.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• 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 3 years.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

National Cancer Centre Singapore

Singapore, 168583, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Sengkang General Hospital

Singapore, 544886, Singapore

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pembrolizumab; Capecitabine; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Iain Tan, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 13, 2019
• Study Start: June 12, 2019
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: November 18, 2025

Record last verified: 2025-11

Locations

SG (3)