Clinical trial NCT00245050: Pyridoxine in Preventing Hand-Foot Syndrome in Patients Who Are Receiving Liposomal Doxorubicin for Cancer
Official title: A Double-Blind Randomized Trial of Pyridoxine Versus Placebo for the Prevention of Doxil-Related Palmar-Plantar Erythrodysesthesia (Hand-Foot Syndrome)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Drug/Agent Toxicity by Tissue/Organ
Endometrial Cancer
Fallopian Tube Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Keywords: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-27
Enrollment: 34
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Palmar-plantar Erythrodysesthesia (PPE)
timeFrame: Treatment repeats every 4 weeks for up to 6 courses in the absence of unacceptable toxicity.
Secondary outcomes:
measure: Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy (FACT-G)
timeFrame: After Cycle 3 of chemotherapy (on average at 3 months)
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Geauga Regional Hospital
state: Ohio
city: Cleveland
country: United States
facility: Lake/University Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Southwest General Health Center
state: Ohio
city: Cleveland
country: United States
facility: University Suburban Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Westlake Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Chagrin Highlands Medical Center
state: Ohio
Study officials:
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Vivian von Gruenigen, MD
role: PRINCIPAL_INVESTIGATOR
References: