A Phase II Study Of Single Agent Depsipeptide (FK228) In Recurrent, Platinum Sensitive Adeno-Carcinoma Of The Ovary Or Peritoneum
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed primary ovarian epithelial or peritoneal
cavity cancer
- Histologic confirmation of recurrent disease not required
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques (including palpation, plain x-ray, CT scan, or MRI) OR ≥ 10
mm by spiral CT scan
- Achieved a complete response after initial prior platinum-containing (cisplatin or
carboplatin) chemotherapy regimen (e.g., conventional-dose therapy, high-dose
therapy, consolidation therapy, or extended therapy after surgical or nonsurgical
assessment)
- Patients who have not received paclitaxel or docetaxel as initial therapy may
receive a second regimen containing these drugs
- No prior chemotherapy for persistent or recurrent disease, including
re-treatment with the original regimen
- Platinum-sensitive disease, defined as having a treatment-free interval with no
evidence of progressive disease for > 6 but < 12 months after completion of a
platinum-based regimen
- No known brain metastases
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- ECOG 0-2 OR
- Karnofsky 60-100%
Life expectancy
- More than 6 months
Hematopoietic
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Renal
- Creatinine ≤ 1.5 times ULN OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- No New York Heart Association class III or IV congestive heart failure
- No myocardial infarction within the past year
- No uncontrolled dysrhythmias
- No poorly controlled angina
- No history of serious ventricular arrhythmia (e.g., ventricular tachycardia or
ventricular fibrillation, ≥ 3 beats in a row)
- QTc interval < 500 msec
- No other significant cardiac disease
Other
- Potassium normal
- Magnesium normal
- No uncontrolled electrolyte abnormality (hypokalemia and hypomagnesemia)
- No ongoing or active infection requiring antibiotics
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to study drug
- No neuropathy ≥ grade 2
- No other uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior monoclonal antibodies, cytokines, or signal transduction inhibitors for
recurrent disease
- No concurrent biologic therapy
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
for the primary malignancy
- No prior FR901228 (depsipeptide)
- No other concurrent chemotherapy
Endocrine therapy
- More than 4 weeks since prior hormonal therapy for the primary malignancy
- Concurrent estrogen replacement therapy allowed
Radiotherapy
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to > 25% of bone marrow
- No concurrent radiotherapy
Surgery
- Not specified
Other
- Recovered from all prior therapy
- More than 4 weeks since prior noncytotoxic therapy for the primary malignancy
- No other prior noncytotoxic therapy for recurrent disease
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No other concurrent drugs known to have histone deacetylase inhibitor activity (e.g.,
valproic acid)
- No concurrent agents that cause QTc prolongation
- No other concurrent investigational agents
- No other concurrent anticancer agents