A Phase II Trial of Doxil and Multiday Vinorelbine in Patients With Metastatic Breast Cancer
Study design: Phase II trial of monthly Doxil® and vinorelbine on day 1 and 2 in women with
metastatic breast cancer.
Treatment plan: Patients will continue therapy, until they have unacceptable toxicity or
Primary endpoint: Response rate
Secondary endpoints: Time to progression, overall survival and toxicity.
Additional study objectives: Evaluation of treatment-related dyspnea, with measurement of
pulse oximetry during and after drug administration, and rigorous study of patients who
experience dyspnea. Palmar-plantar erythrodysesthesia (PPE) will be treated with one of 2
randomly assigned topical salves, measuring duration and severity of symptoms.
Eligibility: Women who have had prior chemotherapy in the adjuvant or metastatic setting, or
both, up to 3 prior regimens. Patients having more than one prior regimen for metastatic
disease must have a performance status of 0 or 1; others may have 0-2. No prior Doxil® or
vinorelbine therapy. Patients are ineligible if prior anthracycline dose is greater than 400
mg/m2, or if they have primary anthracycline-refractory disease, with disease progression
during treatment or with relapse/recurrence within 6 months after last dose of
anthracycline. Patients must have normal neurologic, hematologic, renal and hepatic
functional parameters. Asymptomatic brain metastases are permissible.
Treatment plan: Doxil® 40 mg/m2 IV infusion over 60 minutes on day 1 Vinorelbine 15 mg/m2
IV over 6 minutes on days 1 and 2 Dexamethasone 4 mg IV or 8 mg po (Doxil® pretreatment)
Heparin 5000 U IV (Vinorelbine pretreatment) Pyridoxine (vitamin B6) 200 mg po qd Repeat
every 28 days.
For anemia (hematocrit < 35): Procrit® 40,000 U q wk For neutropenia (ANC < 1,000/mm3 ):
Prophylactic antibiotics (Cipro® or Septra®) For all cycles after neutropenic
fever/infection or grade 3-4 stomatitis: Prophylactic Neulasta® 6 mg SQ on day 3 (This
intervention may be adopted for all patients, all cycles, if 2 of the first 4 patients
enrolled need it.) For PPE: randomize between 2 topical salves and document duration and
severity of sx
Dose adjustments: Subsequent cycles are given on day 29 or after recovery or to grade 0-1
toxicity, with no more than 3 weeks delay. Reduce dose of both drugs by 25% if grade 3 or 4
stomatitis or palmar-plantar or grade 4 thrombocytopenia. Reduce dose of Doxil® ONLY by
50-75% if abnormal bilirubin, alkaline phosphatase and/or ALT, AST (appendix 14.3)
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Leslie R Laufman, MD
Hematology Oncology Consultants, Inc
United States: Institutional Review Board
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