Preoperative CRT With Temozolomide Plus Capecitabine in Rectal Cancer

NCT01781403 | Completed Phase 1 Results

• 1 other identifier: ML28381
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators planned a phase I study of preoperative CRT with capecitabine plus temozolomide inpatients with locally advanced resectable rectal cancer: 1) the role of temozolomide as a radiosensitizer has been well established, 2) hypermethylation (or low expression) of MGMT promoter is associated with colorectal carcinogenesis, can be found in 20\~40% of colorectal cancer patients, and this proportion could be adequate for validation as its role of predictive biomarker, and 3) temozolomide can be additive or synergistic because radiotherapy is now essential in the treatment of rectal cancer.

Conditions

Rectal Cancer

Keywords

Temozolomide; capecitabine; rectal cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  The MTD is defined as the maximum dose level in the doses of temozolomide tested with capecitabine and radiation in which the incidence proportion of DLT exceeds 30%.

  5-6 weeks during study treatment

• Recommended Dose (RD)

  RD will be defined as one level below the MTD.

  5-6 weeks after CRT

Secondary Outcomes (1)

• Pathological Complete Response

  at the time of surgery (6-8 weeks after study treatment)

Other Outcomes (3)

• Toxicity(Adeverse Event)

  5-6 weeks during study treatment

• Efficacy: Pathologic Major Responses

  after surgery (6-8 weeks after study treatment)

• Disease-free Survival

  3-year or 5-year after surgery

Study Arms (1)

Capecitabine, Temozolomide, Radiotherapy

EXPERIMENTAL

The total dose of radiotherapy will be 50.4 Gy, with a daily dose of 1.8 Gy administered on 5 days of each week, comprising a total of 45 Gy to the whole pelvis, followed by a 5.4 Gy boost to the primary tumor. The doses and schedules for capecitabine will be fixed, with only temozolomide being prescribed using a dose-escalation schedule. Capecitabine and temozolomide will be administered during radiotherapy with drug holidays (weekend break).

Drug: Temozolomide

Interventions

Temozolomide DRUG

Preoperative chemoradiotherapy with fixed dose of capecitabine and temozolomide, the dose of temozolomide will be escalated for finding MTD and RD.

Also known as: Capecitabine, preoperative radiotherapy

Capecitabine, Temozolomide, Radiotherapy

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 T3-4 or N+ by rectal MRI with or without endorectal ultrasound
• Available tumor samples before study treatment (fresh or paraffin-embedded) for immunohistochemistry (IHC) and methylation-specific PCR (MSP) to investigate MGMT expression and hypermethylation
• Male or female aged over 20 years
• Be ambulatory and have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• No prior systemic treatment (chemotherapy, immunotherapy) or radiation therapy
• Adequate major organ functions as following:
• 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:

• Histology other than adenocarcinoma or tumor arising from inflammatory bowel disease
• Inadequate tumor sample for MGMT IHC or MSP
• Any evidence of systemic metastasis
• Unresected synchronous colon cancer
• Intestinal obstructions or impending intestinal obstruction, but bypass surgery (colostomy or ileostomy) is permitted before study treatment
• Uncontrolled or severe cardiovascular disease
• 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.
• Patients receiving a concomitant treatment with drugs interacting with 5-FU such as flucytosine, phenytoin, or warfarin et al.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Known hypersensitivity to any of the components of the study medications.

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, Songpa-gu, 138-736, South Korea

Location

Related Publications (1)

• Jeong JH, Hong YS, Park Y, Kim J, Kim JE, Kim KP, Kim SY, Park JH, Kim JH, Park IJ, Lim SB, Yu CS, Kim JC, Kim TW. Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer. Int J Radiat Oncol Biol Phys. 2016 Oct 1;96(2):289-295. doi: 10.1016/j.ijrobp.2016.05.009. Epub 2016 May 17.

  PMID: 27473815 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Temozolomide; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Tae Won Kim
• Organization: Asan Medical Center

twkimmd@amc.seoul.kr

+82-2-3010-3910

Study Officials

• Tae Won Kim, Professor

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 21, 2013
• First Posted: February 1, 2013
• Study Start: May 10, 2013
• Primary Completion: September 3, 2014
• Study Completion: May 4, 2016
• Last Updated: February 4, 2021
• Results First Posted: June 23, 2016

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)