Phase I Clinical Trial of Temsirolimus and Vinorelbine in Advanced Solid Tumors.
Inclusion Criteria
Inclusion
- Patients with histologically confirmed metastatic or unresectable solid tumors for
which standard curative measures do not exist or are no longer effective; histology
will be limited to those tumors for which temsirolimus or vinorelbine have reported
clinical activity: lung, breast, ovary, cervix, prostate, uterus, renal, bladder and
neuroendocrine tumors
- SWOG performance status of 0-2
- Projected life expectancy of at least 3 months
- Provision of informed consent prior to any study-related procedures
- Negative pregnancy test for women of childbearing potential
- Female patients must not be pregnant due to the potential mutagenicity and
teratogenicity of this treatment; a pregnancy test must be administered 7 days prior
to administration of therapy to women of childbearing potential; patients must agree
to use some form of contraception while on this study at initiation and for the
duration of participation in the study; sexually active males must also use a
reliable and appropriate method of contraception; post-menopausal women must be
amenorrheic for at least 12 months to be considered of nonchildbearing potential
- Patients must have recovered from acute toxicities from previous surgery,
chemotherapy or radiation therapy
- ANC >= 1500/mm^3
- Platelet count >= 100,000 cells/mm^3
- Hemoglobin >= 9.0g/dL
- Serum creatinine =< 1.5 mg/dl
- Hepatic function: Patients must have adequate liver functions: AST or ALT =< 2.5 X
upper limit of normal (ULN), alkaline phosphatase =< 2.5 X upper limit of normal; in
patients with bone metastasis and no evidence of liver metastasis and bilirubin =<
upper limit of normal an alkaline phosphatase =< 5 ULN will be allowed
- Serum Bilirubin =< 1.0 mg/dL
- Peripheral neuropathy grade 0-1
- No other concomitant therapy directed at the cancer is allowed
Exclusion
- Prior therapy with vinorelbine or an mTor inhibitor
- Receipt of any investigational agents within 30 days prior to commencing study
treatment
- Last dose of prior chemotherapy discontinued less than 4 weeks before the start of
study therapy
- Last radiation therapy within the last 4 weeks before the start of study therapy,
except palliative radiotherapy
- Any unresolved toxicity greater than CTC grade 1 from previous anticancer therapy,
excluding alopecia
- CTC Grade 1 or greater neuropathy (motor or sensory) at study entry
- Hematologic function with absolute neutrophils =< 1500/mm^3 and/or platelets <
100,000/mm^3
- Hepatic function with serum bilirubin greater than the upper institutional limits of
normal, ALT and AST > 2.5 times the upper institutional limits of normal
- Concurrent use of strong inhibitors of CYP3A4: ketoconazole, itraconazole, ritonavir,
amprenavir, indinavir, nelfinavir, delavirdine and voriconazole
- CYP3A4 inducers should be avoided or used with caution; the use of these agents is
discouraged: rifabutin, rifampicin, rifapentine, carbamazepine, Phenobarbital,
phenytoin and St. John's wart
- Ongoing long term use of steroids for chronic conditions