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

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 3

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

Treatments: Dietary Supplement: pyridoxine hydrochloride; Drug: doxorubicin HCL liposome; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00245050

CASE5Y03 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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34 participants in 2 patient groups, including a placebo group

Pyridoxine

Experimental group

Description:

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.

Treatment:

Dietary Supplement: pyridoxine hydrochloride

Drug: doxorubicin HCL liposome

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: doxorubicin HCL liposome

Drug: Placebo