Colorectal Cancer
Conditions
Keywords
adenocarcinoma of the rectum, stage II rectal cancer, stage III rectal cancer
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.
Interventions
DIETARY_SUPPLEMENTselenomethionine
DRUGcapecitabine
DRUGoxaliplatin
OTHERlaboratory biomarker analysis
OTHERpharmacological study
PROCEDUREadjuvant therapy
PROCEDUREneoadjuvant therapy
PROCEDUREtherapeutic conventional surgery
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Pathological Response Rate | After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically. |
| Rate of T-downstaging With Capecitabine, Oxaliplatin, Selenomethionine, and Radiotherapy | After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Intensity | During treatment with capecitabine, oxaliplatin, selenomethionine. | — |
| Local Relapse Rate | For up to 5 years following surgery. | — |
| Distant Relapse Rate | For up to 5 years following surgery. | — |
| Safety and Tolerability as Assessed by NCI CTCAE Version 3.0 | Adverse events were queried for and collected every cycle for the duration of treatment. | Number of participants with any adverse event as assessed by NCI CTCAE version 3.0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine, Oxaliplatin, Selenomethionine and Radiation Ther 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 | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 1 |
Baseline characteristics
| Characteristic | Capecitabine, Oxaliplatin, Selenomethionine and Radiation Ther |
|---|---|
| Age, Continuous | 56.48 years STANDARD_DEVIATION 6.8 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Complete Pathological Response Rate
Time frame: After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically.
Population: Due to the study's early termination, as a result of low accrual, target accrual was not reached and no data was not collected for this assessment.
Primary
Rate of T-downstaging With Capecitabine, Oxaliplatin, Selenomethionine, and Radiotherapy
Time frame: After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically.
Population: Due to the study's early termination, as a result of low accrual, target accrual was not reached and no data was collected for this assessment.
Secondary
Distant Relapse Rate
Time frame: For up to 5 years following surgery.
Population: Due to the study's early termination, as a result of low accrual, target accrual was not reached and no data was not collected for this assessment.
Secondary
Dose Intensity
Time frame: During treatment with capecitabine, oxaliplatin, selenomethionine.
Population: Due to the study's early termination, as a result of low accrual, target accrual was not reached and no data was collected for this assessment.
Secondary
Local Relapse Rate
Time frame: For up to 5 years following surgery.
Population: Due to the study's early termination, as a result of low accrual, target accrual was not reached and no data was collected for this assessment.
Secondary
Safety and Tolerability as Assessed by NCI CTCAE Version 3.0
Number of participants with any adverse event as assessed by NCI CTCAE version 3.0.
Time frame: Adverse events were queried for and collected every cycle for the duration of treatment.
Population: All treated and eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Capecitabine, Oxaliplatin, Selenomethionine, Radiation Therapy | Safety and Tolerability as Assessed by NCI CTCAE Version 3.0 | 5 Participants |