Capecitabine, Oxaliplatin, Selenomethionine, and Radiation Therapy in Treating Patients Undergoing Surgery For Newly Diagnosed Stage II or III Rectal Adenocarcinoma

NCT ID: NCT00625183

Last Updated: 2017-11-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2009-12-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Selenomethionine may slow the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together With selenomethionine and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well selenomethionine works when given together with capecitabine, oxaliplatin, and radiation therapy in treating patients undergoing surgery for newly diagnosed stage II or stage III rectal cancer.

Detailed Description

OBJECTIVES:

Primary

• To determine the complete pathological response rate of the combination of capecitabine, oxaliplatin, selenomethionine, and radiotherapy in patients with stage II or III rectal adenocarcinoma.
• To determine the T-downstaging rate with this regimen in patients with stage II or III rectal adenocarcinoma.

Secondary

• To determine the safety of this regimen by assessing toxicity and dose intensity of the various components of this regimen.
• To determine the rate of local relapse.
• To determine the rate of distant relapse.

OUTLINE: Patients receive neoadjuvant therapy comprising oral selenomethionine twice daily for 1 week prior to radiotherapy and then once daily for 6 weeks. Patients also receive oxaliplatin IV over 2 hours on days 1-7 and oral capecitabine twice daily on days 1-5 for 6 weeks and undergo radiotherapy 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after completion of neoadjuvant therapy, patients undergo curative-intent surgery. Beginning 4-8 weeks after surgery, patients may receive up to 9 courses of standard adjuvant combination chemotherapy (FOLFOX).

Blood samples are collected at baseline and weekly during treatment and analyzed by absorption spectrophotometry for selenium measurement of drug concentration. Pharmacokinetic studies are also performed.

After completion of study treatment, patients are followed for up to 5 years.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the rectum; stage II rectal cancer; stage III rectal cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Capecitabine, Oxaliplatin, Selenomethionine, Radiation Therapy

Oxaliplatin: 50 mg/m2 weekly x 5 Capecitabine 725 mg/m2BID on days of RT Selenomethionine: 4000mcg/m2 PO BID X 7 days prior to RT, then 4000mcg/m2 PO QD from first to last day of RT, including weekends

Group Type: EXPERIMENTAL

selenomethionine

Intervention Type: DIETARY_SUPPLEMENT

capecitabine

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

selenomethionine

Intervention Type: DIETARY_SUPPLEMENT

capecitabine

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

therapeutic conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed rectal adenocarcinoma that is involving the distal 12 cm of the rectum (above the anal verge)

• Staged within 8 weeks prior to initiation of study by endoscopic ultrasound OR MRI or CT scan if endorectal ultrasound is non-conclusive or non-tolerable
• T3-T4 tumor or evidence of lymph node involvement defined by the presence of at least 1 enlarged peri-rectal lymph node
• No evidence of distant or known metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
• Life expectancy > 1 year
• Leukocytes ≥ 3,000/µL
• Absolute neutrophil count ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Total bilirubin ≤ upper limit of normal (ULN)
• AST/ALT ≤ 2.5 times ULN
• Creatinine ≤ ULN OR creatinine clearance ≥ 60 mL/min
• Able to receive oral medication
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent or previous malignancies unless disease free for > 5 years (excluding nonmelanoma skin cancer)
• No neuropathy ≥ grade 2
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or selenomethionine
• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to the pelvis
• No prior chemotherapy
• No other concurrent investigational or anticancer agents or therapies
• No concurrent vitamin B6 supplementation (except as part of a standard, multivitamin supplement)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marwan Fakih, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Other Identifiers

RPCI-I-113607

Identifier Type: -

Identifier Source: secondary_id

I 113607

Identifier Type: -

Identifier Source: org_study_id