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

Roswell Park Comprehensive Cancer Center

Status and phase

Terminated

Phase 2

Conditions

Colorectal Cancer

Treatments

Radiation: radiation therapy

Procedure: neoadjuvant therapy

Drug: capecitabine

Procedure: therapeutic conventional surgery

Procedure: adjuvant therapy

Dietary Supplement: selenomethionine

Other: laboratory biomarker analysis

Other: pharmacological study

Drug: oxaliplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00625183

RPCI-I-113607

I 113607

Details and patient eligibility

About

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.

Full 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.

Enrollment

5 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

5 participants in 1 patient group

Capecitabine, Oxaliplatin, Selenomethionine, Radiation Therapy

Experimental group

Description:

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

Treatment: