Phase I Study of Vorinostat in Combination With Docetaxel in Patients With Advanced and Relapsed Solid Malignancies.

Study Overview
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Brief Summary
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Vorinostat (Suberoylanilide Hydroxamic Acid; NSC 701852) is a drug that inhibits an enzyme that plays a key role in the regulation of cell survival, growth, and eventual cell death, all of which play a role in cancer. As a result, this drug has the potential to affect a tumor's ability to survive. Vorinostat is the most potent drug of its kind that is currently under investigation in clinical trials. The primary objective of this study is to define the maximum safest dose of vorinostat in combination with a standard chemotherapy agent, docetaxel, in patients with advanced and relapsed lung, bladder, or prostate cancer.

Detailed Description
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Vorinostat (also known as Suberoylanilide Hydroxamic Acid) is a new investigational drug that is not approved by the Food and Drug Administration. This drug has shown promising activity against a number of cancers. We want to determine if treatment with vorinostat in combination with a standard type of chemotherapy (docetaxel [Taxotere™]) is safe and possibly better than treatment with docetaxel alone. We also want to find out more about how patients and the cancer will react to the drugs, what happens to vorinostat in the human body (how your body reacts to this drug and breaks it down) and about its side effects when used in combination with chemotherapy (docetaxel). The purpose of this study is to: Test the safety of the research study drug, vorinostat To determine if any toxicities or severe side effects occur when combining vorinostat with docetaxel (a standard chemotherapy treatment) To study how your body takes in, breaks down and responds to vorinostat To obtain more evidence of the ability of vorinostat to react against cancer, such as the kind that you have. The use of vorinostat in combination with chemotherapy such as docetaxel may result in improved response of the cancer to treatment. Indeed, vorinostat may have an added benefit with docetaxel by promoting cancer cell death. This is because both drugs can interfere with the ability of the cancer to grow, although the way vorinostat does this is not clearly defined. Vorinostat and docetaxel both can disrupt the cancer's ability to produce daughter cancer cells and therefore, the administration of vorinostat before docetaxel is hoped to be better then either drug alone.

Official Title
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A Phase I Study of Suberoylanilide Hydroxamic Acid (Vorinostat) (NSC 701852) in Combination With Docetaxel in Patients With Advanced and Relapsed Solid Malignancies

Conditions
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Prostate Cancer, Bladder Cancer, Urothelial Carcinoma, Non-Small-Cell Lung Carcinoma

Intervention / Treatment
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* Drug: vorinostat (suberoylanilide hydroxamic acid)
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: There is no limit on prior courses of chemotherapy as long as the regimen did not contain docetaxel. Prior use of paclitaxel (Taxol) or other taxanes is permissible. Only patients with non-small cell lung, prostate, and bladder/urothelial cancer that has progressed after chemotherapy or after hormone therapy. Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 3 weeks. Patients may not be receiving any other investigational agents nor had prior treatment with histone deacetylase (HDAC) inhibitors (i.e. Valproic acid, PXD-001, Depsipeptide, MS-275 and LAQ-824) Significant cardiovascular disease including congestive heart failure

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: docetaxel plus vorinostat<br> | Drug: vorinostat (suberoylanilide hydroxamic acid)<br>* Vorinostat will be administered by mouth as a pill for the first 14 days on a continuous basis during of each 21-day cycle (2 weeks of treatment, 1 week break).<br>* Other names: Zolinza,NSC 701852;Drug: docetaxel<br>* Docetaxel will be administered as an intravenous infusion (through the vein) on day 4 of each 21-day cycle.<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The TITE-CRM dose escalation scheme will be used in this study to determine the maximum tolerated dose (MTD) of the combination therapy. |  | After 25 evaluable patients are accrued, a final set of side-effect estimates will be produced for each dose level, and the MTD will be the highest dose with a side-effect estimate at or below the target toxicity estimate of 30%. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Although response is not the primary endpoint of this trial, patients with measurable disease will be assessed by standard criteria. |  | For the purposes of this study, tumor response will be assessed every 6 weeks. | 
| To evaluate the blood levels of vorinostat and docetaxel when administered in combination. |  | All blood levels of the drugs will be conducted during the first cycle of chemotherapy only. |