Clinical trial NCT00625183: Capecitabine, Oxaliplatin, Selenomethionine, and Radiation Therapy in Treating Patients Undergoing Surgery For Newly Diagnosed Stage II or III Rectal Adenocarcinoma
Official title: A Phase II Study of Capecitabine, Oxaliplatin and Selenomethionine and Radiation Therapy in Patients With Stage II and III Rectal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
stage II rectal cancer
stage III rectal cancer
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-28
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Complete Pathological Response Rate
timeFrame: After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically.
measure: Rate of T-downstaging With Capecitabine, Oxaliplatin, Selenomethionine, and Radiotherapy
timeFrame: After completion of capecitabine, oxaliplatin, selenomethionine, and radiation, and before surgery. Assessed endoscopically.
Secondary outcomes:
measure: Safety and Tolerability as Assessed by NCI CTCAE Version 3.0
timeFrame: Adverse events were queried for and collected every cycle for the duration of treatment.
measure: Dose Intensity
timeFrame: During treatment with capecitabine, oxaliplatin, selenomethionine.
measure: Local Relapse Rate
timeFrame: For up to 5 years following surgery.
measure: Distant Relapse Rate
timeFrame: For up to 5 years following surgery.
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Marwan Fakih, MD
role: PRINCIPAL_INVESTIGATOR
References: