Pyridoxine in Preventing Hand-Foot Syndrome in Patients Who Are Receiving Liposomal Doxorubicin for Cancer

A Double-Blind Randomized Trial of Pyridoxine Versus Placebo for the Prevention of Doxil-Related Palmar-Plantar Erythrodysesthesia (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 randomized clinical trial is studying pyridoxine to see how well it works compared to a placebo in preventing hand-foot syndrome in patients who are receiving liposomal doxorubicin for recurrent ovarian, fallopian tube, or peritoneal cancer, metastatic breast cancer, or advanced endometrial cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cavity Cancer; Endometrial Cancer; Drug/Agent Toxicity by Tissue/Organ
• Intervention / Treatment: Dietary supplement: pyridoxine hydrochloride; Drug: doxorubicin HCL liposome; Drug: Placebo

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of pyridoxine vs placebo in preventing palmar-plantar erythrodysesthesia (PPE) in patients receiving doxorubicin HCl liposome for recurrent ovarian, fallopian tube, or peritoneal cavity cancer, metastatic breast cancer, or advanced endometrial cancer.
• Compare quality of life in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to cancer type (ovarian, fallopian tube, or peritoneal cavity cancer vs breast cancer vs endometrial cancer). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive doxorubicin HCl liposome IV 40mg/m2 over 1 hour on day 1 and oral pyridoxine 100 mg twice daily on days 1-28.
• Arm II: Patients receive doxorubicin HCl liposome IV 40mg/m2 over 1 hour on day 1 and oral placebo 100 mg twice daily on days 1-28.

In both arms, treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients who develop grade 2-3 palmar-plantar erythrodysesthesia despite dose reduction of doxorubicin HCl liposome are unblinded and removed from the study (for patients in arm I) OR receive oral pyridoxine twice daily beginning day 1 of the next planned therapy (for patients in arm II).

Quality of life is assessed at baseline and after every third course of therapy.

After completion of study treatment, patients are followed periodically for 6 months.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44024
      • Geauga Regional Hospital
    • Cleveland, Ohio, United States, 44060
      • Lake/University Ireland Cancer Center
    • Cleveland, Ohio, United States, 44130
      • Southwest General Health Center
    • Cleveland, Ohio, United States, 44145
      • UHHS Westlake Medical Center
    • Cleveland, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center
    • Cleveland, Ohio, United States, 44143
      • University Suburban Health Center
    • Cleveland, Ohio, United States, 44708
      • UHHS Chagrin Highlands Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Recurrent ovarian, fallopian tube, or peritoneal cavity cancer
  • Metastatic breast cancer
  • Advanced endometrial cancer
• Planning to receive chemotherapy with doxorubicin HCl liposome at a dose of 40 mg/m^2

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Sex

• Not specified

Menopausal status:

• Not specified

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL

Hepatic

• AST and ALT ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2 times ULN
• Bilirubin normal

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• Ejection fraction ≥ 50% by MUGA or 2-D echocardiogram
• No history of cardiac disease
• No New York Heart Association class II-IV heart disease
• No clinical evidence of congestive heart failure

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No active infection requiring antibiotics
• No history of hypersensitivity reaction attributed to a conventional formulation of doxorubicin HCl or doxorubicin HCl liposome and any of its components
• No other invasive malignancy within the past 5 years except nonmelanoma or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 3 weeks since prior biologic or immunologic agents for this cancer

Chemotherapy

• Recovered from prior chemotherapy

  • Alopecia or neuropathy allowed
• No prior doxorubicin HCl liposome

• Other concurrent chemotherapy allowed provided palmar-plantar erythrodysesthesia is not one of the side effects of the therapy

  • No concurrent cytarabine, fluorouracil, liposomal daunorubicin, or capecitabine
  • No concurrent pre-medication with corticosteroids as part of the chemotherapy regimen

Endocrine therapy

• See Chemotherapy
• At least 3 weeks since prior and no concurrent oral or topical corticosteroids

• At least 1 week since prior hormonal therapy for this cancer

  • Concurrent hormone replacement therapy allowed

Radiotherapy

• At least 3 weeks since prior radiotherapy for this cancer and recovered

Surgery

• Recovered from prior surgery

Other

• At least 3 weeks since prior and no other concurrent forms of pyridoxine except what is included in a multivitamin
• No prior anticancer treatment that contraindicates study treatment
• No concurrent amifostine or other protective agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pyridoxine; Arm I: Patients receive doxorubicin HCl liposome IV 40 mg/m2 over 1 hour on day 1 and oral pyridoxine 100 mg twice daily on days 1-28.	Dietary supplement: pyridoxine hydrochloride; Arm I: Patients receive doxorubicin HCl liposome IV 40 mg/m2 over 1 hour on day 1 and oral pyridoxine twice 100 mg daily on days 1-28.; Drug: doxorubicin HCL liposome; IV, 40mg/m2
PLACEBO_COMPARATOR: Placebo; Arm II: Patients receive doxorubicin HCl liposome IV 40 mg/m2 over 1 hour on day 1 and oral placebo twice 100 mg daily on days 1-28.	Drug: doxorubicin HCL liposome; IV, 40mg/m2; Drug: Placebo; Arm II: Patients receive doxorubicin HCl liposome IV 40 mg/m2 over 1 hour on day 1 and oral placebo 100 mg twice daily on days 1-28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Palmar-plantar Erythrodysesthesia (PPE)	Patients were monitored weekly with phone calls from the research nurse and monthly at clinic visits for overall (including pyridoxine) and specific doxorubicin HCl liposome related toxicities using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.	Treatment repeats every 4 weeks for up to 6 courses in the absence of unacceptable toxicity.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy (FACT-G)	QOL was measured with the FACT-G questionnaire following the third course of doxorubicin HCl liposome before the patient was seen by the treating physician and before chemotherapy was administered. The FACT-G, version 4, is a 27-item core questionnaire evaluating the domains of physical, functional, family-social, and emotional well-being (PWB, FWB, SWB, EWB). Total score ranges from 0-108 and higher scores indicate better QOL.	After Cycle 3 of chemotherapy (on average at 3 months)

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): September 1, 2011

Study Registration Dates

• First Submitted: October 25, 2005
• First Submitted That Met QC Criteria: October 25, 2005
• First Posted (ESTIMATE): October 27, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2011
• Last Update Submitted That Met QC Criteria: December 28, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; recurrent ovarian epithelial cancer; male breast cancer; fallopian tube cancer; stage IV endometrial carcinoma; recurrent endometrial carcinoma; drug/agent toxicity by tissue/organ; stage III endometrial carcinoma; peritoneal cavity cancer
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Adnexal Diseases; Breast Diseases; Fallopian Tube Diseases; Dermatitis; Drug Eruptions; Drug Hypersensitivity; Breast Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Drug-Related Side Effects and Adverse Reactions; Hand-Foot Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Micronutrients; Antibiotics, Antineoplastic; Vitamins; Vitamin B Complex; Doxorubicin; Liposomal doxorubicin; Vitamin B 6; Pyridoxine
• Other Study ID Numbers: CASE5Y03 (OTHER: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract)