Oxaliplatin, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Rectum

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00086931
• Other study ID #: I 10803
• Secondary ID: RPCI-I-10803SANO
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 8, 2004
• Last updated: March 7, 2013
• Start date: September 2003
• Est. completion date: May 2010

Study information

• Verified date: March 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Oxaliplatin and capecitabine may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin and capecitabine when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for locally advanced cancer of the rectum. NOTE: *The phase I portion of this trial closed 06/2005. The best dose of oxaliplatin and capecitabine has been determined.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 2010
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• capecitabine
oral dose escalating, twice daily.
• oxaliplatin
IV over 2 hours on days 1, 8, 15, 22, and 29.

Procedure:
• conventional surgery
curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy
• neoadjuvant therapy
chemotherapy and radiation prior to surgery

Radiation:
• radiation therapy
once daily 5 days a week for 5.5 weeks

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (2)

Fakih MG, Bullarddunn K, Yang GY, Pendyala L, Toth K, Andrews C, Rustum YM, Ross ME, Levea C, Puthillath A, Park YM, Rajput A. Phase II study of weekly intravenous oxaliplatin combined with oral daily capecitabine and radiotherapy with biologic correlates — View Citation

Fakih MG, Rajput A, Yang GY, et al.: A phase I and biological correlates study of capecitabine (CAP) + oxaliplatin (OX) + radiation therapy (RT) in locally advanced rectal cancer (LARC). [Abstract] J Clin Oncol 23 (Suppl 16): A-3633, 279s, 2005.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete pathological response rate at time of surgery		Time of surgery	No
Secondary	Disease-free survival, safety, and overall survival at 5 years		Continuous	Yes