RATIONALE: Drugs used in chemotherapy, such as doxorubicin and carboplatin, work in different
ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Giving doxorubicin together with carboplatin may kill more tumor cells.
PURPOSE: This phase I and phase II trial is studying the side effects and best dose of
carboplatin when given together with doxorubicin to see how well it works in treating
patients with recurrent ovarian cancer.
- To determine the maximum tolerated dose and safety of intravenous doxorubicin
hydrochloride and intraperitoneal carboplatin in patients with platinum-sensitive
recurrent ovarian cancer.
- To evaluate the feasibility of this regimen in these patients.
- To evaluate the response rate and progression-free survival of patients with recurrent
ovarian cancer who have had no more than two prior salvage regimens.
OUTLINE: This is a phase I dose-escalation study of carboplatin followed by a phase II study.
- Phase I: Patients receive doxorubicin hydrochloride IV over 1 hour followed by
carboplatin intraperitoneally on day 1 until the maximum tolerated dose is achieved.
Treatment repeats every 28 days for 6 courses in the absence of disease progression or
- Phase II: Patients receive doxorubicin hydrochloride as in phase I and carboplatin at
the maximum tolerated dose as in phase I.
After completion of study treatment, patients are followed every 4 weeks for 1 year.
PROJECTED ACCRUAL: A total of 61 patients (18 patients in phase I and 43 patients in phase
II) will be accrued for this study.
- Histologically confirmed ovarian carcinoma
- Recurrent disease
- Known platinum-sensitive recurrent disease after no more than 2 prior salvage regimens
- Measurable disease as defined by a target lesion and a CA125 level
- No epithelial ovarian carcinoma of low malignant potential
- GOG performance status 0, 1, or 2
- Life expectancy > 6 months
- Absolute neutrophil count ≥ 1,500/uL
- Platelet count ≥ 100,000/uL
- Hemoglobin > 9.0 g/dL
- Creatinine ≤ 2.0 mg/dL
- Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- SGOT and alkaline phosphatase ≤ 3 x ULN
- Neuropathy (sensory and motor) ≤ CTCAE grade 1
- GOG performance status 3 or 4
- Pregnant or breastfeeding
- History of hypersensitivity reactions attributed to a conventional formulation of
doxorubicin hydrochloride or the components of DOXIL®
- Abnormal LVEF as determined by gated cardiac radionucleotide scan (MUGA)
- Septicemia or severe infection
- Acute hepatitis or severe gastrointestinal bleeding
- Any of the following:
- Unstable angina
- Myocardial infarction within the past 6 months
- NYHA class II-IV heart failure
- Uncontrolled angina
- Severe uncontrolled ventricular arrhythmias
- Clinically significant pericardial disease
- Electrocardiographic evidence of acute ischemic or active conduction system
- Patients with evidence of abnormal cardiac conduction (e.g., bundle branch
block or heart block) are eligible if their disease has been stable for the
past six months
- Other invasive malignancies within the past 5 years except for nonmelanoma skin cancer
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 6 months since prior adjuvant regimen
- At least 4 weeks since prior salvage treatment
- May have received secondary cytoreduction for recurrent ovarian cancer
- May have received prior intraperitoneal therapy for ovarian cancer
- May have received no more than 2 prior platinum and taxane-based regimens
- May have received prior intraperitoneal platinum during front-line treatment
- Prior anthracycline dose exceeding 360 mg/m^2 for doxorubicin hydrochloride (including
DOXIL®) or 720 mg/m^2 for epirubicin hydrochloride
- Prior radiotherapy
- Prior intraperitoneal carboplatin or cisplatin as salvage treatment for recurrent
- Concurrent amifostine or other protective agents