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

A Phase II Study of Capecitabine, Oxaliplatin and Selenomethionine and Radiation Therapy in Patients With Stage II and III Rectal Adenocarcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: pharmacological study; Radiation: radiation therapy; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Drug: oxaliplatin; Drug: capecitabine; Dietary supplement: selenomethionine

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Other: pharmacological study; Radiation: radiation therapy; Other: laboratory biomarker analysis; Procedure: therapeutic conventional surgery; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Drug: oxaliplatin; Drug: capecitabine; Dietary supplement: selenomethionine

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Adverse events were queried for and collected every cycle for the duration of treatment.
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.

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marwan Fakih, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: February 26, 2008
• First Submitted That Met QC Criteria: February 26, 2008
• First Posted (Estimate): February 28, 2008

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: October 13, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage II rectal cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Capecitabine; Oxaliplatin; Selenium
• Other Study ID Numbers: I 113607; RPCI-I-113607