A Phase II Study of SB-715992 (NSC-727990, IND-70273) in Advanced Renal Cell Cancer
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed renal cell carcinoma
which is metastatic (M1); histopathology is not restricted; patients with
unresectable primary tumor (but MO) are also eligible
- Patients must have measurable disease; x-rays, scans or physical examinations used
for tumor measurement must have been completed within 28 days prior to registration;
x-rays, scans or physical examinations for non-measurable disease must have been
completed within 42 days prior to registration
- Patients with metastatic disease who have a resectable primary tumor and are deemed a
surgical candidate may have undergone resection and have recovered from surgery; at
least 28 days must have elapsed since surgery and patient must have recovered from
any adverse effects of surgery
- Patients must have discontinued therapy due to toxicity or demonstrated progression
of disease following a minimum of one prior therapy; prior therapies may include:
immunotherapy with either interferon (IFN) and/or Interleukin-2 (IL-2) or prior
anti-angiogenesis agents; at least 28 days must have elapsed since the last
treatment; patients must have recovered from any adverse effects of prior therapy
- Patients may have received prior radiation therapy; at least 21 days must have
elapsed since completion of prior radiation therapy; patients must have recovered
from all associated toxicities at the time of registration
- Patients may not have received prior tubule, DNA, or mitosis targeting agents for the
treatment of renal cell carcinoma
- Patients must have a ECOG performance status of 0 - 2
- Pregnant or nursing women may not participate in this trial; women and men of
reproductive potential must have agreed to use an effective contraceptive method;
women of child-bearing potential must have a negative urine pregnancy test
- Patients with a history of brain metastases or who currently have treated or
untreated brain metastases are not eligible; patients with clinical evidence of brain
metastases must have a brain CT or MRI negative for metastatic disease within 56 days
prior to registration
- Absolute granulocyte count (AGC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9 mg/dl, and a
platelet count ≥ 100,000 cells/mm3 within 14 days prior to registration
- Patients must have a total bilirubin < 2 mg/dl obtained within 14 days prior to
registration
- Patients must have SGOT and SGPT =< 2.5 x institutional upper limit of normal within
14 days prior to registration
- Patients must have a serum creatinine =< 2.0 or a calculated creatinine clearance >=
40 mL/min for patients with creatinine levels above institutional normal; this must
be obtained within 14 days prior to registration
- Patients must have a corrected QT interval less than 0.47 seconds
- All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and federal
guidelines
- Prohibited medications; SB-715992 is a moderate to significant in vitro inhibitor of
CYP3A4; the following lists of medications/substances are moderate to significant
inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may
alter study drug exposure; the use of these medications/ substances within 14 days
(=< 6 months for amiodarone) prior to the administration of the first dose of
SB-715992 through discontinuation from the study is prohibited
- Inhibitors of CYP3A4:
- Antibiotics: Clarithromycin, erythromycin, troleandomycin, rifabutin,
rifapentine
- Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day),
voriconazole
- Antidepressants: nefazodone, fluovoxamine
- Calcium channel blockers: verapamil, diltiazem
- Miscellaneous: amiodarone*, bitter orange
- Use of amiodarone within 6 months prior to the administration of the first dose
of SB-715992 is prohibited.
- Inducers of CYP3A4:
- Anticonvulsants: phenytoin, carbamazepine, phenobarbital, oxcarbazepine
- Antibiotics: rifampin, rifabutin, rifapentine
- Miscellaneous: St. John's Wort, modafinil
- Patients must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to SB-715992
- Patients must not have any uncontrolled intercurrent illness including, but not
limited to, ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social
situations that would limit compliance with study requirements
- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving
combination anti-retroviral therapy are not eligible because of possible
pharmacokinetic interactions with SB-715992
- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from
which the patient is currently in complete remission, or any other cancer from which
the patient has been disease-free for 5 years