Phase II Trial of Vinfluinine and Capecitabine in Previously Treated Metastatic Breast Cancer
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed breast cancer meeting the following
criteria:
- Metastatic disease
- Previously treated with 1-2 chemotherapy regimens for metastatic disease
- Measurable disease, defined as ≥ 1 measurable lesion ≥ 2.0 cm by conventional
techniques OR ≥ 1.0 cm by spiral CT scan
- No nonmeasurable disease, including any of the following:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural or pericardial effusion
- Inflammatory breast disease
- Lymphangitis cutis/pulmonis
- Abdominal masses not confirmed and followed by imaging techniques
- Cystic lesions
- Must have received ≥ 1 prior trastuzumab (Herceptin®)-containing regimen (unless
there is a contraindication) if tumor is HER2 positive (3+ by immunohistochemistry or
amplified by fluorescent in situ hybridization [FISH])
- No CNS metastasis unless controlled by prior surgery and/or radiotherapy
- "Controlled" is defined as ≥ 2 months of no symptoms or evidence of progression
- Currently enrolled on clinical trial QOL N0392
- Hormone receptor status not specified
- Hormone-positive tumor must meet at least 1 of the following criteria:
- Tumor refractory to hormonal therapy
- Heavy visceral tumor burden that requires chemotherapy for better and
faster control of metastatic disease
- Relapsed disease during adjuvant hormonal therapy and failed first-line
chemotherapy
- Not treated with hormonal therapy because of side effects or adverse events
PATIENT CHARACTERISTICS:
- Male or female
- Menopausal status not specified
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- Platelet count ≥ 100,000/mm^3
- Hemoglobin > 8.0 g/dL
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase (AP), AST, and ALT must meet 1 of the following criteria:
- AP normal AND AST and ALT ≤ 5 times ULN
- AP ≤ 2.5 times ULN AND AST and ALT ≤ 1.5 times ULN
- AP ≤ 5 times ULN AND AST and ALT normal
- Creatinine clearance ≥ 30 mL/min
- Serum sodium normal
- Not pregnant or nursing
- No nursing during and for 30 days after completion of study therapy
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 30 days after
completion of study therapy
- No history of allergy or hypersensitivity to drug product excipients or to agents
chemically similar to vinflunine and/or capecitabine
- No prior unanticipated severe reaction to fluoropyrimidine therapy
- No known hypersensitivity to fluorouracil
- No known dihydropyrimidine dehydrogenase deficiency
- No active, unresolved infection
- No New York Heart Association class III-IV cardiovascular disease, unstable angina,
myocardial infarction within the past 6 months, or poorly controlled hypertension
- No preexisting neuropathy ≥ grade 2
- No concurrent serious medical condition that would preclude study treatment
- No other stage III or IV invasive cancer within the past 3 years
- No lack of physical integrity of the upper gastrointestinal tract, clinically
significant malabsorption syndrome, or inability to take oral medication
- Ability to complete questionnaires alone or with assistance
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior unlimited hormonal therapy allowed in the neoadjuvant, adjuvant, or metastatic
setting
- No major surgery, chemotherapy, or immunologic therapy within the past 4 weeks
- No radiotherapy within the past 4 weeks, except if to a nontarget lesion only
- Prior radiotherapy to a target lesion is allowed if there has been clear
progression of the lesion since radiotherapy was completed
- If patient received single-dose radiotherapy or palliation to a nontarget lesion
only, the patient may immediately proceed to study registration without waiting
4 weeks
- No prior fluoropyrimidines, including capecitabine, or vinca alkaloids (e.g.,
vinorelbine, vinblastine, vincristine, or vindesine) for metastatic breast cancer
- No prior radiotherapy to > 30% of bone marrow-containing areas
- No cimetidine, allopurinol, sorivudine, or brivudine within the past 2 weeks
- No ketoconazole, itraconazole, ritonavir, amprenavir, or indinavir within the past 2
weeks
- No concurrent treatment in another clinical trial in which investigational procedures
are performed or investigational therapies are administered
- No concurrent trastuzumab (Herceptin®)
- No concurrent hormonal therapy
- No concurrent interleukin-11
- No other concurrent chemotherapeutic agents, biologic agents, or radiotherapy
- No concurrent administration of any of the following:
- Cimetidine
- Allopurinol
- Sorivudine
- Brivudine
- Ketoconazole
- Itraconazole
- Ritonavir
- Amprenavir
- Indinavir
- Wwarfarin allowed if patient is on a stable dose and has an INR < 3.0