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Colorectal CancerPhase 2NCT03984578

Window of Opportunity Study in Colorectal Cancer

A Phase 2 study testing CAPEOX, Pembrolizumab and Capecitabine/ 5-FU in people with Colorectal Cancer, run by National Cancer Centre, Singapore at 3 sites in Singapore.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 100 years
Conditions the study is for
Colorectal Cancer
What is being tested?
CAPEOX, Pembrolizumab and Capecitabine/ 5-FU
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
3 sitesSingapore
Study dates
12 Jun 2019to 28 Feb 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • 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 14 days prior to the start of study treatment.
  • Adequate Organ Function Laboratory:
  • Absolute neutrophil count (ANC): ≥1500/μL.
  • Platelets: ≥100 000/μL.
  • Hemoglobin: ≥9.0 g/dL or ≥5.6 mmol/L.
  • Creatinine OR Measured or calculated creatinine clearance: ≤1.5 × Upper Limit of Normal (ULN) OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
  • Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN.
  • Alanine Aminotransferase and Aspartate Aminotransferase: ≤2.5 × ULN.
  • Coagulation - International normalized ratio (INR) OR prothrombin time (PT) OR Activated partial thromboplastin time (aPTT): ≤1.5 × ULN.
  • Are not on current anti-HCV treatment for subjects with chronic infection by HCV. For subjects who have had anti-HCV therapy, the last dose of anti-HCV medication should be at least 4 weeks before first dose of pembrolizumab.
  • Note: Screening for chronic HCV infection will be done if subject's HCV status is not already known.
  • Have HBV viral load under 100 IU/mL with or without treatment, for subjects with chronic hepatitis B infection.
  • HBV viral load must be less than 100 IU/mL on at least 4 weeks of anti-viral therapy prior to first dose of pembrolizumab. Subjects on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment. Subjects who are anti-HBc (+), negative for HBs Ag, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis

Who cannot join

  • 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).
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  • 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.
  • 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 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, 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.
  • Has dual active HBV infection [HBsAg (+) and/or detectable HBV DNA] and HCV infection [anti-HCV Ab (+) and detectable HCV RNA] at study entry.

Trial locations and contacts

3 sites in 1 country.

Singapore3 sites

  • National Cancer Centre Singapore

    Singapore, 168583

  • Singapore General Hospital

    Singapore, 169608

  • Sengkang General Hospital

    Singapore, 544886

Other trials in Singapore

About this study

Official title: Window of Opportunity Study With Neoadjuvant Pembrolizumab in Colorectal Cancer

This is a window of opportunity translational study investigating the use of pre-operative pembrolizumab and chemotherapy or chemoradiotherapy in non-metastatic colorectal cancer.

Read the detailed description

Patients with radiologically-assessed locally advanced non-metastatic colorectal cancer will receive the following treatment before surgery:

Newly Diagnosed Colon cancers:

One cycle of CAPEOX chemotherapy Two cycles of Pembrolizumab on Day 1 (concurrent with CAPEOX chemotherapy) and Day 22.

Newly Diagnosed Rectal cancers:

Following completion of chemo-radiotherapy with 5-fluorouracil (5-FU)/ capecitabine, patients will receive 2 cycles of Pembrolizumab given 3 weeks apart.

Colon and Rectal Cancer Patients Referred for Pre-Operative Chemotherapy:

Neoadjuvant pembrolizumab 200 mg 3-weekly for a maximum of 6 doses to be administered along with XELOX chemotherapy and additional 1 dose pembrolizumab 200 mg followed by standard of care (SOC) tumour resection.

Pre-operative biopsy and surgical samples as well as blood will be collected for translational studies.

Being tested
CAPEOX, Pembrolizumab, Capecitabine/ 5-FU, CAPEOX/Pembrolizumab, Pembrolizumab alone
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CAPEOXDrug

    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

  • PembrolizumabDrug

    Also called Keytruda

    IV infusion of 200mg on Day 1 and Day 22

  • Capecitabine/ 5-FUDrug

    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

  • PembrolizumabDrug

    Also called Keytruda

    IV infusion of 200mg on Day 1 of each cycle

  • CAPEOX/PembrolizumabDrug

    • 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.

  • Pembrolizumab aloneDrug

    Also called Keytruda

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

  • Surgical resectionProcedure or surgery

    Performed after all medical intervention.

Study groups in NCT03984578
Study groupRoleWhat they receive
Newly Diagnosed Colon cancersExperimentalPre-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.
Receives: Drug: CAPEOX; Drug: Pembrolizumab; Procedure: Surgical resection
Newly Diagnosed Rectal CancersExperimentalFollowing completion of neo-adjuvant chemo-radiotherapy, 2 cycles of pre-operative Pembrolizumab administered 3 weeks apart.
Receives: Drug: Capecitabine/ 5-FU; Drug: Pembrolizumab; Procedure: Surgical resection
Newly Diagnosed Colon and Rectal Cancers Referred for Pre-Operative ChemotherapyExperimentalNeoadjuvant pembrolizumab 3-weekly for a maximum of 6 doses to be administered along with XELOX chemotherapy, and additional 1 dose pembrolizumab.
Receives: Drug: CAPEOX/Pembrolizumab; Drug: Pembrolizumab alone; Procedure: Surgical resection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. Pathology regression

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

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

  3. 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.

    Measured: 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)

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

    Single cell RNA sequencing, bulk genomics \& bulk transcriptomics will be used to describe the enrichment of different immune cell states or cell types

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

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

    Flow cytometry will be used to determine the proportions of immune cell types with specific lineage marker expression including CD45, CD4, CD8, PDL1 and LAG3

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

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

    Functional assays of immune cell immunoreactivity will be used to determine the proportion of target cell kill of paired immune cell and target cell

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2019
  2. Study start12 Jun 2019
  3. Primary completion28 Feb 2025
  4. Study completion28 Feb 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03984578
Sponsor's protocol ID
WoOCRC
Status last verified
Nov 2025
First submitted
4 Jun 2019
Last updated
18 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CAPEOX, Pembrolizumab and Capecitabine/ 5-FU in people with Colorectal Cancer, run by National Cancer Centre, Singapore at 3 sites in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumour immune gene expression signature (time frame: From time of first tumour biopsy before treatment to time of tumour resection performed 1-3 weeks after last dose of neoadjuvant treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03984578.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.

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