Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Recurrent Advanced Ovarian Epithelial or Peritoneal Cavity Cancer

OBJECTIVES:

I. Determine the response rate, time to progression, and survival of patients with recurrent advanced ovarian epithelial or primary peritoneal cavity cancer treated with gemcitabine hydrochloride and 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin).

II. Determine the toxicity of this regimen in these patients. III. Correlate the effect of 17-AAG alone on chaperone and client proteins in tumor samples and peripheral blood mononuclear cells with response, time to progression, and survival of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to gemcitabine hydrochloride therapy (gemcitabine hydrochloride-naive/no prior exposure to gemcitabine hydrochloride vs gemcitabine hydrochloride-resistant/prior exposure to gemcitabine hydrochloride as a single agent with disease progression while on treatment). Patients receive tanespimycin intravenously (IV) over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

Inclusion criteria

• Diagnosis of ovarian epithelial or primary peritoneal cavity cancer

• Relapsed disease
• Persistent disease
• Platinum-resistant disease, defined as having evidence of disease that would be expected to be non-responsive to additional platinum-containing regimens or contraindication to platinum-based chemotherapy and 1 of the following:

• Failure to obtain a complete response to initial platinum therapy
• Recurrence < 6 months after completing a platinum-containing regimen for initial or recurrent disease
• Any of the above situations and following treatment with additional chemotherapy regimens (e.g., non-platinum containing regimens)
• Relative or absolute contraindication to platinum-based chemotherapy regimens (e.g., platinum allergy) as determine by the investigator
• Measurable or evaluable disease

• Patients with a rising CA 125 level, even in the absence of other indicators of disease, allowed provided CA 125 is ≥ 2 times upper limit of normal (ULN)
• Patients with accessible disease must be willing to undergo tumor biopsies
• No CNS metastases
• Performance status - ECOG 0-2
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Bilirubin normal
• Alkaline phosphatase ≤ 2.5 times ULN
• AST ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN
• Ejection fraction > 40% by ECHO for patients with prior anthracycline therapy
• No significant cardiac disease including any of the following:

• New York Heart Association class III or IV heart disease
• History of myocardial infraction within the past year
• Uncontrolled dysrhythmias or requirement for antiarrhythmic drugs
• Poorly controlled angina
• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No history of QTc ≥ 500 msec
• No active ischemic heart disease within the past 12 months
• No congenital long QT syndrome
• No left bundle branch block
• No cardiac symptoms ≥ grade 2
• No history of cardiac toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone, bleomycin, or carmustine)
• Does not meet the medicare criteria for home oxygen
• No pulse oximetry at rest and exercise < 88%
• No symptomatic pulmonary disease requiring medication including any of the following:

• Dyspnea on or off exertion
• Paroxysmal nocturnal dyspnea
• Oxygen requirement
• Significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease)
• No pulmonary symptoms ≥ grade 2
• No history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone, bleomycin, or carmustine)
• K+, Mg ++, and Ca ++ normal
• No seizure disorder
• No uncontrolled infection
• No history of serious allergic reaction to eggs
• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent immunotherapy
• No concurrent routine or prophylactic colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
• Prior gemcitabine hydrochloride allowed provided 1 of the following criteria is met:

• Patients have no prior exposure to gemcitabine hydrochloride
• Patients who have prior exposure to gemcitabine hydrochloride as a single agent have experienced progressive disease while on treatment
• No other concurrent chemotherapy
• No prior radiotherapy to > 25% of bone marrow
• No history of radiotherapy that potentially included the heart in the field (e.g., mantle)

• Chest wall irradiation or other radiotherapy techniques that do not include the heart in the radiation field area allowed
• More than 4 weeks since prior radiotherapy
• More than 4 weeks since prior radiopharmaceuticals
• No concurrent radiotherapy
• No other concurrent investigational therapy
• No concurrent medications that may prolong QTc