Pyridoxine in Preventing Hand-Foot Syndrome in Patients Who Are Receiving Capecitabine for Advanced Colorectal Cancer or Breast Cancer

A Randomised Placebo-controlled Study Evaluating the Role of Pyridoxine in Controlling Capecitabine-induced Hand-foot Syndrome

RATIONALE: Pyridoxine (vitamin B6) may prevent or lessen hand-foot syndrome caused by chemotherapy. It is not yet known whether pyridoxine is more effective than a placebo in preventing hand-foot syndrome.

PURPOSE: This phase III randomized trial is studying pyridoxine to see how well it works compared to a placebo in preventing hand-foot syndrome in patients who are receiving capecitabine for advanced colorectal cancer or breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Colorectal Cancer; Palmar-plantar Erythrodysesthesia
• Intervention / Treatment: Other: placebo; Procedure: quality-of-life assessment; Dietary supplement: pyridoxine hydrochloride

Detailed Description

OBJECTIVES:

Primary

• Determine whether pyridoxine can reduce the incidence of capecitabine dose modifications (dose delay and dose reductions) due to toxicity.

Secondary

• Determine the incidence of hand-foot syndrome (HFS).
• Determine the overall toxicity.
• Determine the quality of life.
• Determine the response to chemotherapy.
• Determine the progression-free survival.
• Determine the level of biomarkers which might predict the occurrence of HFS.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (breast cancer vs colorectal cancer). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral pyridoxine hydrochloride 3 times daily beginning with the initiation of capecitabine chemotherapy and continuing until completion of chemotherapy.
• Arm II: Patients receive oral placebo 3 times daily beginning with the initiation of capecitabine chemotherapy and continuing until completion of chemotherapy.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Evidence of hand-foot syndrome is assessed at baseline and before each course of capecitabine. Quality of life is assessed at baseline and then every 6 weeks.

After completion of study treatment, patients are followed at 6 and 12 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 270
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Basildon, England, United Kingdom, SS16 5NL
      • Basildon University Hospital
    • Bedford, England, United Kingdom, MK42 9DJ
      • Primrose Oncology Unit
    • Bury St. Edmunds, England, United Kingdom, IP33 2QZ
      • West Suffolk Hospital
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
    • Canterbury, England, United Kingdom, CT2 7NR
      • Kent and Canterbury Hospital
    • Derby, England, United Kingdom, DE1 2QY
      • Derbyshire Royal Infirmary
    • Exeter, England, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
    • King's Lynn, England, United Kingdom, PE30 4ET
      • Queen Elizabeth Hospital
    • Lancanshire, England, United Kingdom, WN1 2NN
      • Royal Albert Edward Infirmary
    • Maidstone, England, United Kingdom, ME16 9QQ
      • Mid Kent Oncology Centre at Maidstone Hospital
    • Peterborough, England, United Kingdom, PE3 6DA
      • Peterborough Hospitals Trust
    • Plymouth, England, United Kingdom, PL6 8DH
      • Derriford Hospital
    • Swindon, England, United Kingdom, SN3 6BB
      • Great Western Hospital
    • Tunbridge Wells, England, United Kingdom, TN4 8AT
      • Kent and Sussex Hospital
    • Walsall, England, United Kingdom, WS2 9PS
      • Walsall Manor Hospital
    • Westcliff-On-Sea, England, United Kingdom, SS0 0RY
      • Southend University Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of advanced colorectal or breast carcinoma

  • Hormone receptor status not specified
• Receiving single-agent capecitabine chemotherapy
• Measurable disease for response assessment, determined on an individual patient basis, using conventional clinical and/or radiological methods

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Menopausal status not specified
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100,000 mm^3
• WBC ≥ 3,000/mm^3
• ANC ≥ 1,500/mm^3
• Bilirubin ≤ 1.3 x upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 x ULN
• AST and ALT ≤ 5 x ULN
• Creatinine ≤ 1.5 x ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial
• No medical or psychiatric condition which would influence the ability to provide informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 6 weeks since prior investigational agents
• Concurrent radiotherapy allowed
• No other concurrent chemotherapy or immunotherapy

• No concurrent nonsteroidal anti-inflammatory drugs NSAIDs) for the primary purpose of treating hand-foot syndrome (HFS) or cancer

  • NSAIDs for conditions other than HFS or cancer allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence of capecitabine dose modifications (dose delay and dose reductions) due to toxicity

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Quality of life
Overall toxicity
Response to chemotherapy
Incidence of hand-foot syndrome (HFS)
Measurement of biomarkers that might predict the occurrence of HFS

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Study Chair: Pippa Corrie, PhD, FRCP, Cambridge University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: breast cancer; rectal cancer; male breast cancer; colon cancer; palmar-plantar erythrodysesthesia
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Breast Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Drug Eruptions; Drug Hypersensitivity; Breast Neoplasms; Colorectal Neoplasms; Hand-Foot Syndrome; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Vitamin B 6; Pyridoxine
• Other Study ID Numbers: CRCA-CCTC-CAPP-IT; CDR0000576453 (Registry Identifier: PDQ (Physician Data Query)); EUDRACT-2004-000325-29; EU-20786; ISRCTN82842634; CCLG-CAPP-IT