Intensity-Modulated Radiation Therapy With Incorporated Boost and Capecitabine Before Surgery in Treating Patients With Locally Advanced Rectal Cancer

Temple University Health System (TUHS)

Status and phase

Completed

Phase 1

Conditions

Colorectal Cancer

Treatments

Drug: capecitabine

Procedure: neoadjuvant therapy

Procedure: conventional surgery

Radiation: radiation therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00084591

P30CA006927 (U.S. NIH Grant/Contract)

FCCC-03606

CDR0000365462

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Intensity-modulated radiation therapy (radiation directed at the tumor more precisely than in standard radiation therapy) with incorporated boost (an increase in the amount of radiation given during treatment) may cause less damage to normal tissue. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy together with chemotherapy before surgery may shrink the tumor so it can be removed.

PURPOSE: This phase I trial is studying the side effects and best dose of neoadjuvant intensity-modulated radiation therapy with incorporated boost when given together with capecitabine in treating patients with locally advanced rectal cancer.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose of neoadjuvant boost intensity-modulated radiotherapy when combined with capecitabine before surgery in patients with locally advanced rectal cancer.

Secondary

Determine the pathologic tumor response in patients treated with this regimen.
Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of boost intensity-modulated radiotherapy (IMRT).

Patients undergo neoadjuvant IMRT with incorporated boost once daily 5 days a week for 5 weeks. Beginning on the first day of radiotherapy, patients receive oral capecitabine twice daily 7 days a week for 5 weeks. Patients undergo surgical resection 4-8 weeks after completion of chemoradiotherapy.

Cohorts of 3-6 patients undergo escalating doses of boost IMRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline, at week 5 of chemoradiotherapy, before surgery, and then at 1, 3, and 12 months after surgery.

Patients are followed at 1, 3, and 12 months after surgery.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for this study.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary adenocarcinoma of the rectum
- Distal border of the tumor within 12 cm of the anal verge by proctoscopic exam
- Clinical stage T3-4, N1-2 (stage II or III) disease by 2 of the following tests:
  - Physical exam
  - Transrectal ultrasound
  - Pelvic CT scan
  - Pelvic MRI
No clinical evidence of metastatic disease

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

More than 3 months

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
No known, uncontrolled coagulopathy

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
SGOT and SGPT ≤ 1.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN

Renal

Creatinine ≤ 1.5 times normal
Creatinine clearance > 50 mL/min

Cardiovascular

No clinically significant cardiac disease
No congestive heart failure
No symptomatic coronary artery disease
No poorly controlled cardiac arrhythmias
No myocardial infarction within the past year

Gastrointestinal

No active inflammatory bowel disease
No lack of physical integrity of the upper gastrointestinal tract
No malabsorption syndrome

Other

No other prior or concurrent malignancy except inactive, non-invasive carcinoma of the cervix or non-melanoma skin cancer
No concurrent serious, uncontrolled infection(s)
No prior unanticipated severe reaction to fluoropyrimidine therapy
No known sensitivity to fluorouracil
No prior uncontrolled seizures
No CNS disorders that would preclude study participation
No other medical or psychiatric condition that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy