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

Breast Cancer Clinical Trial

Official title:

A Double-Blind Randomized Trial of Pyridoxine Versus Placebo for the Prevention of Doxil-Related Palmar-Plantar Erythrodysesthesia (Hand-Foot Syndrome)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00245050
• Other study ID #: CASE5Y03
• Secondary ID: P30CA043703CASE5
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2005
• Last updated: December 28, 2011
• Start date: April 2004
• Est. completion date: September 2011

Study information

• Verified date: December 2011
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: September 2011
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Drug/Agent Toxicity by Tissue/Organ
• Endometrial Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Hand-Foot Syndrome
• Ovarian Cancer
• Peritoneal Cavity Cancer
• Peritoneal Neoplasms

Intervention

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:
• 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.
• doxorubicin HCL liposome
IV, 40mg/m2

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Geauga Regional Hospital	Cleveland	Ohio
United States	Lake/University Ireland Cancer Center	Cleveland	Ohio
United States	Mercy Cancer Center at Mercy Medical Center	Cleveland	Ohio
United States	Southwest General Health Center	Cleveland	Ohio
United States	UHHS Chagrin Highlands Medical Center	Cleveland	Ohio
United States	UHHS Westlake Medical Center	Cleveland	Ohio
United States	University Suburban Health Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	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)	No