Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Docetaxel

Androgens

Hormones

Mitogens

Tyrosine Kinase Inhibitors

Imatinib Mesylate

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

One treatment cycle is defined as 21 days.

Docetaxel: 70 mg/m\^2 (60 mg/m\^2 was tested in Phase I as well), Intravenous, every 21 days.

One treatment cycle is defined as 21 days.

Imatinib Mesylate: 24-36 hours after Docetaxel, 600 mg (400 mg was tested in Phase I as well), orally, daily x 14 days.

Anna Ferrari, MD

This trial is designed to determine the proper doses of Docetaxel and Imatinib mesylate to be used to treat hormone refractory prostate cancer and to evaluate the safety and efficacy of the treatment.

Androgen-independent prostate cancer is the second most common cause of cancer death in men. These patients have limited treatment options. Docetaxel(Taxotere) is the single most active agent for the treatment of hormone refractory prostate cancer. Phase II clinical trials including docetaxel combinations with other microtubule inhibitors have shown 60-70% prostate specific antigen (PSA) declines greater than 50% and 30-40% measurable disease responses. However, the duration of response is limited to roughly 22 weeks. Combinations with new agents are needed to increase the rate and duration of response over existing docetaxel containing combinations.

The platelet derived growth factor receptor(PDGFR)and platelet derived growth factor (PDGF) A are frequently expressed (80%) in primary and bone marrow metastasis of human prostate cancer (PC). Recent experimental evidence suggests that activation of PDGFR/PDGF can be oncogenic in the development and/or progression of PC. There is also evidence that PC cells that express PDGF promote PDGFR expression in endothelial cells and neo- angiogenesis. Together, these experimental evidence supports that inhibition of PDGFR may be of therapeutic benefit to advanced prostate cancer patients.

Gleevec (Imatinib mesylate ) is a potent inhibitor of PDGFR. Consistent with these observations, treatment with Gleevec in an experimental prostate cancer mouse model was better than paclitaxel alone in reducing bone metastasis but the antitumor effect was strongest with the combination of both. In a phase I study of heavily pretreated hormone refractory PC patients, Gleevec 600 mg/daily lead-in for 30 days followed by Gleevec 600 mg/daily with Paclitaxel 30mg/m2 weekly x4 weeks every 6 weeks induced a \>50% PSA decline in 7% and 38% of patients respectively with acceptable toxicity. These observations suggested that this combination merits further investigation.

With high-dose docetaxel (70mg/m\^2) being the single most active agent in hormone refractory prostate cancer and no data existing in the use of high-docetaxel with Gleevec, a phase I/II study to determine the maximum tolerated dose (MTD) of the combination and optimum dose for a phase II trial is warranted.

Gleevec is expected to affect the activation status of sensitive receptor tyrosine kinase targets and associated signaling effectors in the tumor cells and the neovasculature. However, it is not fully established to what extent alterations of the target and /or other molecules in the signaling pathway are essential for Gleevec's antitumor activity in prostate cancer patients. It is also unknown whether preexisting molecular changes in the prostate tumors of individual patients could affect Gleevec's activity even in the presence of the targets. Therefore, an assessment of the expression levels and/or presence of mutations of selected molecules in specimens of patients in clinical trials may contribute in various ways: 1. to understand the requirements to elicit or inhibit a response to the combination, 2. whether adding other targeted agents may improve response and/or 3. whether selection of patients that might benefit should be based on the tumor profile. Thus, whenever possible specimens form the primary and/or metastatic sites should be retrieved and/or obtained to perform these analyses.

Docetaxel (Taxotere) and Imatinib Mesylate (Gleevec) in Hormone Refractory Prostate Cancer

Phase I/II, Open Label Study of Sequential Taxotere® (Docetaxel) and Gleevec® (Imatinib Mesylate) in Hormone Refractory Prostate Cancer

PSA response is defined as a greater than or equal to a 50% decrease in PSA from the baseline without clinical or radiologic evidence of progression according to the Response Evaluation Criteria in Solid Tumors (RECIST). PSA concentration was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy.

PSA was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy.

Measurable disease response is defined as the number of participants whose best response is complete response or partial response over the number of patients with measurable desease according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Time to PSA pregression is defined as the time at which therapy statred and ends when the PSA increased by 50% above the nadir confirmed on a second determination.

Overall survival time is the time from the start of therapy till death. Median overall survival reported here is the time when 50% of the participants are alive.

Novartis

NYU Langone Health

adverse events were collected by patient reporting, investigator questioning, physical exams, lab tests, etc.

21 days per treatment cycle for up to 1 year: Day 1: Docetaxel (Taxotere) ( 70 mg/m\^2 intravenously over 1 hour. Day 2: (24-36 hours later) start Gleevec (Imatinib Mesylate) 600 mg, orally, daily x 14 days

Docetaxel +Gleevec

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

This study was terminated before it reached the target accrual number due to slow accrual, leading to small number of subjects analyzed (12 out of the target number of 37).

The analysis was based on intent-to-treat population.

Percentage of Participants With Prostate Specific Antigen (PSA) Response

The analysis was based on intent-to-treat population

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Docetaxel (Taxotere) and Imatinib Mesylate (Gleevec) in Hormone Refractory Prostate Cancer	NCT00861471	Prostate Cancer Prostatic Neopl...	Docetaxel Imatinib Mesyla...	18 Years -	NYU Langone Health
Docetaxel (Taxotere) and Imatinib Mesylate (Gleevec) in Hormone Refractory Prostate Cancer	NCT00861471	Prostate Cancer Prostatic Neopl...	Docetaxel Imatinib Mesyla...	18 Years -	NYU Langone Health

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