Breast Cancer, Drug/Agent Toxicity by Tissue/Organ, Endometrial Cancer, Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Conditions
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
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.
Interventions
DIETARY_SUPPLEMENTpyridoxine 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.
DRUGPlacebo
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.
IV, 40mg/m2
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | 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
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy (FACT-G) | 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. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the outpatient gynecologic oncology clinics at University Hospitals from May 2004 to December 2007.
Pre-assignment details
Patients were required to have discontinued corticosteroid therapy at least three weeks prior to enrollment and no corticosteroids were allowed for the duration of the trial. Patients must have discontinued pyridoxine therapy at least three weeks prior to enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Pyridoxine 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. | 18 |
| Placebo 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. | 16 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | Pyridoxine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 14 Participants |
| Age Continuous | 65.9 years STANDARD_DEVIATION 11 | 62.9 years STANDARD_DEVIATION 9.4 | 64.3 years STANDARD_DEVIATION 10.2 |
| Region of Enrollment United States | 16 participants | 18 participants | 34 participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 15 | 10 / 14 |
| serious Total, serious adverse events | 8 / 15 | 6 / 14 |
Outcome results
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.
Time frame: Treatment repeats every 4 weeks for up to 6 courses in the absence of unacceptable toxicity.
Population: Patients were evaluable for PPE/HFS(Hand-Foot Syndrome) incidence and toxicity assessment if they received at least one course of chemotherapy. Intention to treat analysis was used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pyridoxine | Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | Grade 1 HFS | 2 participants |
| Pyridoxine | Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | Grade 2 HFS | 3 participants |
| Pyridoxine | Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | Grade 3 HFS | 3 participants |
| Placebo | Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | Grade 1 HFS | 3 participants |
| Placebo | Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | Grade 2 HFS | 3 participants |
| Placebo | Number of Participants With Palmar-plantar Erythrodysesthesia (PPE) | Grade 3 HFS | 1 participants |
Comparison: Based on published literature, it is estimated that the incidence of HFS for all grades is 49%. A decrease of 50% or more in the incidence of HFS in patients receiving pyridoxine would be of clinical significance. A sample size of 27 patients per group was chosen as this would allow us to detect a difference between HFS incidence of 49% and 11.5% (alpha=0.05, two-sided, power=0.80). Interim analysis was conducted after 30 patients were enrolled and had evaluable HFS assessment data.p-value: <0.0595% CI: [0.536, 2.16]Chi-squared
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.
Time frame: After Cycle 3 of chemotherapy (on average at 3 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pyridoxine | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy (FACT-G) | 84.9 Total scores on FACT-G scale | Standard Deviation 10.2 |
| Placebo | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy (FACT-G) | 84.4 Total scores on FACT-G scale | Standard Deviation 9.5 |
p-value: 0.916t-test, 2 sided