A Study to Evaluate the Safety, Tolerability, and Activity of Lonafarnib and Docetaxel (Study P04467AM1)(TERMINATED)

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Two-Part Study to Determine the Safety, Tolerability, and Activity of Lonafarnib and Docetaxel

Conditions
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Prostate Cancer, Breast Cancer, Ovarian Cancer, Lung Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: Docetaxel plus lonafarnib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel plus lonafarnib (single arm)<br>Docetaxel plus lonafarnib | Drug: Docetaxel plus lonafarnib<br>* Docetaxel: 60-75 mg/m2 Lonafarnib: 150-375 mg PO BID<br>* Other names: Docetaxel (Taxotere®); lonafarnib (SCH 066336, Sarasar®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 |