Know Cancer

forgot password

A Randomized, Phase II Study of Concurrent Radiotherapy and Oxaliplatin, Capecitabine With or Without Cetuximab in Rectal Cancer Tumor Stratified by KRAS Mutation Status.

Phase 2
21 Years
Open (Enrolling)
Rectal Cancer

Thank you

Trial Information

A Randomized, Phase II Study of Concurrent Radiotherapy and Oxaliplatin, Capecitabine With or Without Cetuximab in Rectal Cancer Tumor Stratified by KRAS Mutation Status.

Aims: The primary aim of this study is to estimate the pathological complete response rate
following neoadjuvant radiotherapy with concurrent capecitabine and oxaliplatin (CAPOX),
with or without cetuximab based on the KRAS mutation status in rectal cancer.

Hypothesis: Cetuximab, a monoclonal antibody targeted against the EGF receptor, is active in
metastatic colorectal cancer and a radio-sensitizer. In colorectal cancer, the presence of
KRAS mutation has been associated with the absence of response to cetuximab. We hypothesise
that the addition of cetuximab to CAPOX concurrent with neoadjuvant radiotherapy only
benefited patients whose tumours do not have the KRAS mutation and therefore, personalizing
cetuximab therapy based on tumour KRAS mutation status may yield a higher pathological

Methods: This study employed a standard 2-stage Phase II design to evaluate the efficacy and
tolerability of two neoadjuvant chemoradiotherapy regimens. The assignment of the
neoadjuvant chemotherapy will be determined by the KRAS mutation status of the tumor.
Subjects with KRAS mutation will receive CAPOX. Subjects with no KRAS mutation will be
randomized to receive CAPOX +/- cetuximab.Definitive surgery is scheduled for 6-8 weeks
after the completion of chemoradiotherapy. Surgical management will be a sphincter
preservation approach whenever possible, using the total mesorectal excision technique.After
the operation, pathologic evaluation of the surgical specimen will be performed.

Significance:In this proof-of-concept study, we aim to demonstrate that using an enriched
patient cohort to test our hypothesis that the addition of cetuximab will yield a higher
pathological response rate in KRAS mutation-negative rectal cancer. This approach can
potentially identify a subset of patients that may benefit from cetuximab and spare those
who may not benefit from unnecessary treatment toxicities and costs. Our study will help to
prioritise novel targeted agents for a smaller, faster, and less expensive confirmatory
phase III trials.

Inclusion Criteria:

1. All patients must have histologically or cytologically confirmed T3/4 and/or node
positive adenocarcinoma of the rectum with the inferior border within 12 cm from the
anal verge without evidence of distant metastases, as evaluated by computed
tomography, ultrasonography, MRI or clinically.

2. Patients must have normal organ and marrow function as defined below:

leukocytes >3,000/mcL absolute neutrophil count >1,500/mcL platelets >100,000/mcL
total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) greater than
2.5 X institutional upper limit of normal creatinine within normal institutional

3. Age >21 years

4. Patients must have ECOG performance status of 0-2.

5. Patients must be 18 years old or greater.

6. The tumor must be considered by the surgeon to be amenable to curative resection.

7. Ability to understand and the willingness to sign a written informed consent

8. Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately.

Exclusion Criteria:

1. Patients who have had prior chemotherapy or radiotherapy.

2. Patients may not be receiving any other investigational agents.

3. Patients with stage I or IV cancer of the rectum.

4. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab, oxaliplatin or capecitabine.

5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

6. Inability to take oral medications.

7. Pregnant women are excluded from this study because agents use in the study may cause
fetal harm.

8. HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with docetaxel. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy.

9. History of other malignancies within 5 years, except non-melanoma skin cancer, in
situ carcinoma of the cervix or ductal carcinoma of the breast. Previous invasive
cancer permitted if disease-free at least 5 years.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Principal Investigator

Wei Peng Yong, MRCP, MB ChB

Investigator Role:

Principal Investigator

Investigator Affiliation:

National University Hospital, Singapore


Singapore: Health Sciences Authority

Study ID:




Start Date:

July 2008

Completion Date:

Related Keywords:

  • Rectal Cancer
  • tumor
  • Rectal Neoplasms