RATIONALE: Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin,
work in different ways to stop tumor cells from dividing so they stop growing or die.
17-N-allylamino-17-demethoxygeldanamycin may also stop the growth of tumor cells by blocking
the enzymes necessary for their growth.
PURPOSE: This phase II trial is studying how well 17-N-allylamino-17-demethoxygeldanamycin
works in treating patients with metastatic kidney cancer.
- Determine the efficacy of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in patients
with metastatic papillary or clear cell renal cell carcinoma.
- Determine the safety of this drug in these patients.
- Correlate tumor c-met expression with response in patients treated with this drug.
OUTLINE: This is an open-label study. Patients are stratified according to histology
(papillary vs clear cell).
Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-90 minutes on
days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 1 year in the absence of
disease progression or unacceptable toxicity.
Patients are followed at 3 weeks and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 24-74 patients (12-37 per stratum) will be accrued for this
study within 6-20 months (clear cell stratum) and 2-5 years (papillary stratum).
- Histologically confirmed renal cell carcinoma
- Papillary OR clear cell histology
- If other histologies are present, clear cell or papillary must be
- Metastatic disease
- Measurable disease
- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
OR ≥ 10 mm by spiral CT scan
- No brain metastases unless previously treated with radiotherapy or surgery AND
asymptomatic with no active brain metastases detectable by CT scan or MRI for ≥ 6
- 18 and over
- Karnofsky 70-100%
- Not specified
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 2.0 times ULN
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No severe valvular disease
- No severe debilitating pulmonary disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No allergy to egg or egg products
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
- No active or ongoing infection requiring IV antibiotics
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
PRIOR CONCURRENT THERAPY:
- No more than 1 prior cytokine-based regimen
- No concurrent biologic therapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- Not specified
- More than 4 weeks since prior radiotherapy
- No concurrent radiotherapy
- More than 4 weeks since prior major surgery
- Recovered from prior therapy
- No more than 1 prior non-cytokine-based regimen
- No other prior systemic treatment regimens
- No other concurrent cytotoxic therapy
- No other concurrent anticancer therapy
- No other concurrent investigational agents