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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Drug/Agent Toxicity by Tissue/Organ, Endometrial Cancer, Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

Intervention / Treatment
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* Dietary Supplement: pyridoxine hydrochloride
* Drug: Placebo
* Drug: doxorubicin HCL liposome


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyridoxine<br>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<br>* 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.<br>Drug: doxorubicin HCL liposome<br>* IV, 40mg/m2<br>|
| Placebo Comparator: Placebo<br>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: Placebo<br>* 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.<br>Drug: doxorubicin HCL liposome<br>* IV, 40mg/m2<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug/agent toxicity by tissue/organ, fallopian tube cancer, peritoneal cavity cancer, recurrent ovarian epithelial cancer, recurrent endometrial carcinoma, stage III endometrial carcinoma, stage IV endometrial carcinoma, stage IV breast cancer, male breast cancer, recurrent breast cancer