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

• ClinicalTrials.gov Identifier: NCT00245050
• Recruitment Status: Completed
• First Posted: October 27, 2005
• Results First Posted: December 22, 2010
• Last Update Posted: December 30, 2011
• Sponsor: Case Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Case Comprehensive Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Drug/Agent Toxicity by Tissue/Organ; Endometrial Cancer; Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer	Dietary Supplement: pyridoxine hydrochloride; Drug: Placebo; Drug: doxorubicin HCL liposome	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Double-Blind Randomized Trial of Pyridoxine Versus Placebo for the Prevention of Doxil-Related Palmar-Plantar Erythrodysesthesia (Hand-Foot Syndrome)
• Study Start Date: April 2004
• Actual Primary Completion Date: April 2008
• Actual Study Completion Date: September 2011

Arms and Interventions

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: 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.; Drug: doxorubicin HCL liposome; IV, 40mg/m2

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) [ Time Frame: Treatment repeats every 4 weeks for up to 6 courses in the absence of unacceptable toxicity. ]
   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.

Secondary Outcome Measures :

1. Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy (FACT-G) [ Time Frame: After Cycle 3 of chemotherapy (on average at 3 months) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Ohio

Geauga Regional Hospital

Cleveland, Ohio, United States, 44024

Lake/University Ireland Cancer Center

Cleveland, Ohio, United States, 44060

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44106-5065

Southwest General Health Center

Cleveland, Ohio, United States, 44130

University Suburban Health Center

Cleveland, Ohio, United States, 44143

UHHS Westlake Medical Center

Cleveland, Ohio, United States, 44145

Mercy Cancer Center at Mercy Medical Center

Cleveland, Ohio, United States, 44708

UHHS Chagrin Highlands Medical Center

Cleveland, Ohio, United States, 44708

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Vivian von Gruenigen, MD; Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

More Information

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00245050
• Other Study ID Numbers: CASE5Y03; P30CA043703 ( U.S. NIH Grant/Contract ); CASE5Y03 ( Other Identifier: Case Comprehensive Cancer Center )
• First Posted: October 27, 2005
• Results First Posted: December 22, 2010
• Last Update Posted: December 30, 2011
• Last Verified: December 2011

Keywords provided by Case Comprehensive Cancer Center:

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

Additional relevant MeSH terms:

Breast Neoplasms; Endometrial Neoplasms; Fallopian Tube Neoplasms; Hand-Foot Syndrome; Drug-Related Side Effects and Adverse Reactions; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Neoplasms; Uterine Diseases; Fallopian Tube Diseases; Chemically-Induced Disorders; Drug Eruptions; Dermatitis; Drug Hypersensitivity; Pyridoxine; Vitamin B 6; Doxorubicin; Liposomal doxorubicin; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Vitamin B Complex