Preoperative CRT With Capecitabine ± Temozolomide in Patients With LARC

NCT03156036 | Completed Phase 2

• 1 other identifier: TemoCap2
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective biomarker-stratified, randomised phase II study of preoperative CRT with temozolomide plus capecitabine in patients with locally advanced rectal cancer. The primary endpoint is pathologic complete response rates defined as total regression of the primary tumor. For each cohort of MGMT hypermethylated versus MGMT unmethylated, patients will be randomised (ratio 1:1 for each arm) into preoperative CRT with capecitabine or preoperative CRT with temozolomide plus capecitabine arms. According to the prior phase I results, MGMT hypermethylated arm is estimated as 70% of total patients and the target pathologic complete response rate was assumed as 35% in this population when treated with preoperative CRT with temozolomide and capecitabine (15% in the standard treatment arm or those with unmethylated MGMT). Investigator would like to demonstrate the superiority in terms of pathologic complete responses when treated with preoperative CRT with temozolomide plus capecitabine in patients with locally advanced rectal cancer, and to validate the predictive role of MGMT status

Conditions

Advanced Rectal Cancer

Keywords

Temozolomide; Capecitabine; MGMT

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response rate(Pathologic staging and tumor regression grade.)

  Surgery is after the completion of CRT

  6 weeks(maximum 7 weeks)

Study Arms (4)

MGMT hypermethylated Cohort A

EXPERIMENTAL

MGMT hypermethylated Cohort A patients will be randomised into preoperative CRT with temozolomide plus capecitabine arms. (n=86)

Drug: Capecitabine plus temozolomide VS Capecitabine

MGMT hypermethylated Cohort B

ACTIVE COMPARATOR

MGMT hypermethylated B Cohort patients will be randomised into preoperative CRT with capecitabine arms. (n=86)

Drug: Capecitabine plus temozolomide VS Capecitabine

MGMT unmethylated Cohort A

ACTIVE COMPARATOR

MGMT unmethylated A patients will be randomised into preoperative CRT with temozolomide plus capecitabine arms. (n=37)

Drug: Capecitabine plus temozolomide VS Capecitabine

MGMT unmethylated Cohort B

ACTIVE COMPARATOR

MGMT unmethylated B patients will be randomised into preoperative CRT with capecitabine arms. (n=37)

Drug: Capecitabine plus temozolomide VS Capecitabine

Interventions

Capecitabine plus temozolomide VS Capecitabine DRUG

For each cohort of MGMT hypermethylated versus MGMT unmethylated, patients will be randomised (ratio 1:1 for each arm) into preoperative CRT with capecitabine or preoperative CRT with temozolomide plus capecitabine arms. Chemotherapy during preoperative chemoradiotherapy: Capecitabine and temozolomide will be administered during radiotherapy with drug holidays (weekend break). dosage: Capecitabine 825 mg/m2 twice daily, Temozolomide 75 mg/m2/day

Also known as: Temoram, Xeloda

MGMT hypermethylated Cohort A; MGMT hypermethylated Cohort B; MGMT unmethylated Cohort A; MGMT unmethylated Cohort B

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the rectum
• Tumor located within 12cm of anal verge
• Clinical stage of cT3-4Nany (cStage II) or cTanyN1-2 (cStage III) by rectal MRI
• Available tumor samples for methylation-specific PCR (MSP) to investigate MGMT hypermethylation
• Male or female aged over 20 years
• Be ambulatory and have an Eastern Cooperative Oncology Group (ECOG) performance status0-1.
• No prior systemic treatment (chemotherapy, immunotherapy) or radiation therapy
• Adequate major organ functions as following:
• Hematopoietic function: ANC 1,500/mm3, Platelet 100,000/mm3 Hepatic function: serum bilirubin 2.0 mg/dL, AST/ALT levels 2.5 x UNL Renal function: serum creatinine UNL or Cockroft creatinine clearance 50 ml/min
• Be willing and able to comply with the protocol for the duration of the study.
• Give written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

You may not qualify if:

• \- Patients will be exluded from the study for any of the following reasons:
• Histology other than adenocarcinoma or tumor arising from inflammatory bowel disease
• Inadequate tumor sample for MGMT MSP
• Any evidence of systemic metastasis
• Unresected synchronous colon cancer; endoscopically resected synchronous colon cancer of pTis or pT1 is permitted
• Subjects unable to swallow oral medication because of such as current or impending intestinal obstructions, but bypass surgery (colostomy or ileostomy) is permitted before study treatment
• Uncontrolled or severe cardiovascular disease:
• New York Heart Association class III or IV heart disease.
• Unstable angina or myocardial infarction within the past 6 months.
• History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality.
• Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
• Other malignancy within the past 5 years except cured non-melanomatous skin cancer, carcinoma in situ of the cervix, or thyroid papillary carcinoma.
• Organ allografts requiring immunosuppressive therapy.
• Psychiatric disorder or uncontrolled seizure that would preclude compliance.
• Pregnant, nursing women or patients with reproductive potential without contraception.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, Songpa, 05505, South Korea

Location

Related Publications (1)

• Oh CR, Kim JE, Lee JS, Kim SY, Kim TW, Choi J, Kim J, Park IJ, Lim SB, Park JH, Kim JH, Choi MK, Cha Y, Baek JY, Beom SH, Hong YS. Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02. Clin Oncol (R Coll Radiol). 2023 Feb;35(2):e143-e152. doi: 10.1016/j.clon.2022.10.016. Epub 2022 Nov 12.

  PMID: 36376167 DERIVED

MeSH Terms

Interventions

Capecitabine

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 3, 2017
• First Posted: May 17, 2017
• Study Start: November 30, 2017
• Primary Completion: February 2, 2021
• Study Completion: February 2, 2021
• Last Updated: September 7, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)