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A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer


Phase 1/Phase 2
18 Years
75 Years
Not Enrolling
Both
Colorectal Cancer

Thank you

Trial Information

A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer


OBJECTIVES:

Primary

- Determine the maximum tolerated dose of neoadjuvant oxaliplatin and capecitabine when
combined with radiotherapy in patients with locally advanced adenocarcinoma of the
rectum. (Phase I closed to accrual as of 06/2005.)

- Determine the rate of complete pathological response in patients treated with this
regimen.

Secondary

- Determine the overall survival of patients treated with this regimen.

- Determine the rate of local and overall failure in patients treated with this regimen.

- Determine the utility of TS, TP, DPD, ERCC-1, and apoptosis to predict response in
patients treated with this regimen.

- Determine the rate of pathologic down-staging in patients treated with this regimen.

- Determine the safety and toxicity of this regimen in these patients.

- Determine the rate of sphincter-saving rectal surgery in patients treated with this
regimen who had been deemed candidates for abdominoperineal resection at diagnosis.

OUTLINE: This is a multicenter, phase I (phase I closed to accrual as of 06/2005),
dose-escalation study of oxaliplatin and capecitabine followed by a phase II study.

- Phase I (closed to accrual as of 06/2005): Patients undergo radiotherapy once daily 5
days a week for 5.5 weeks and receive oral capecitabine twice daily on days
radiotherapy is administered. Beginning on day 1 of radiotherapy, patients also receive
oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.

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

- Phase II: Patients undergo radiotherapy and receive capecitabine and oxaliplatin as in
phase I at the MTD.

All patients undergo curative-intent surgery 6-8 weeks after the completion of
chemoradiotherapy.

Patients are followed every 3 months for 3 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 31-40 patients (6-15 for phase I [phase I closed to accrual as
of 06/2005] and 25 for phase II) will be accrued for this study within 2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the rectum

- Tumor involving the distal 12 cm of the rectum (above the anal verge)

- Clinically staged by endoscopic ultrasound with one of the following criteria:

- T3-T4 disease

- Evidence of lymph node involvement, defined by the presence of ≥ 1 enlarged
peri-rectal lymph node (≥ 1 cm in size)

- No known distant metastases

PATIENT CHARACTERISTICS:

Age

- 18 to 75

Performance status

- ECOG 0-1 OR

- Karnofsky 70-100%

Life expectancy

- More than 1 year

Hematopoietic

- WBC ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal

Renal

- Creatinine normal OR

- Creatinine clearance ≥ 60 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- Able to receive oral medication

- No other malignancy within the past 5 years except nonmelanoma skin cancer

- No prior or concurrent significant neuropathy

- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to study drugs

- No ongoing or active infection

- No other concurrent uncontrolled illness

- No psychiatric illness or social situation that would preclude study compliance

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception during and for 3
months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent granulocyte-stimulating factors

Chemotherapy

- No prior chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- No prior pelvic radiotherapy

Surgery

- Not specified

Other

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete pathological response rate at time of surgery

Outcome Time Frame:

Time of surgery

Safety Issue:

No

Principal Investigator

Marwan Fakih, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

I 10803

NCT ID:

NCT00086931

Start Date:

September 2003

Completion Date:

May 2010

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the rectum
  • stage III rectal cancer
  • stage II rectal cancer
  • Rectal Neoplasms
  • Colorectal Neoplasms

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263