Breast Cancer, Gastric Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer
Conditions
Brief summary
This study will determine the best doses of docetaxel and lonafarnib when the two anti-cancer agents are used in combination. Patients with tumors for which treatment with docetaxel would be appropriate are eligible. A second part of the study will further examine the effectiveness of the combination treatment in men with prostate cancer.
Interventions
DRUGDocetaxel plus lonafarnib
Docetaxel: 60-75 mg/m2 Lonafarnib: 150-375 mg PO BID
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For Part 1: Subjects may be male or female and must be at least 18 years of age. * For Part 1: Cancer for which docetaxel treatment is appropriate. * For Part 1: Docetaxel-naïve * For Part 2: Subjects must be male and at least 18 years of age. * For Part 2: Subjects must have adenocarcinoma of the prostate confirmed by histologic/cytologic biopsy. * For Part 2: Subjects must have progressive, metastatic, AIPC and a PSA of 10 ng/ml or more after hormonal therapy prior to docetaxel treatment. Progressive disease is defined as a consistently increasing serum PSA level within 28 days prior to docetaxel administration. * Adequate organ function within 3 weeks prior to first study drug administration. * Performance status (ECOG) is less than or equal to 2. * Subject understands and agrees to procedures and participation by signing informed consent form. * Agrees to use medically accepted form of contraception.
Exclusion criteria
* Receipt of or need to continue to receive prohibited medications (listed in the protocol) more recently than the washout period (indicated in the protocol). * Surgery within 3 weeks prior to first study drug administration. * History within 5 years prior to first study drug administration of another malignancy except adequately treated Stage I/II basal/squamous cell skin cancer. * Radiation therapy to more than 25% of his/her total bone marrow during life. * Radiation therapy within 3 weeks prior to first study drug administration. * Known hypersensitivity to prednisone, docetaxel, polysorbate 80, lonafarnib, or any excipients associated with these medications. * Known contraindication to steroid use. * Known leptomeningeal or CNS metastasis. * Heart, vascular, or seizure disorder (detailed list in the protocol) within 6 months prior to first study drug administration. * Baseline QTc interval greater than 450 msec. * Grade 2 or more peripheral neuropathy or drug-related toxicity per CTCAE. Exceptions are noted in the protocol. * Any clinically significant condition or situation that the investigator thinks would interfere with the study evaluations or subject's participation. * Subject is part of staff personnel involved in the study. * Subject has known clinically significant immunosuppression.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events and dose-limiting toxicities | Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity |
| Rate of prostate-specific antigen (PSA) responses | Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with dose-limiting toxicities | Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity |
| Plasma lonafarnib concentrations | Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity |
| RECIST-defined radiological response rate | Until disease progression, unacceptable dose delays or reductions, or unacceptable toxicity |
Outcome results
None listed