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

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

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer; Bladder Cancer; Urothelial Carcinoma; Non-Small-Cell Lung Carcinoma
• Intervention / Treatment: Drug: vorinostat (suberoylanilide hydroxamic acid); Drug: docetaxel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Only patients with non-small cell lung, prostate, and bladder/urothelial cancer that has progressed after chemotherapy or after hormone therapy.

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 3 weeks.
2. 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)
3. Significant cardiovascular disease including congestive heart failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: docetaxel plus vorinostat	Drug: vorinostat (suberoylanilide hydroxamic acid); 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).; Other Names: Zolinza,NSC 701852; Drug: docetaxel; Docetaxel will be administered as an intravenous infusion (through the vein) on day 4 of each 21-day cycle.; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Deborah Bradley, MD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: November 27, 2007
• First Submitted That Met QC Criteria: November 28, 2007
• First Posted (Estimate): November 29, 2007

Study Record Updates

• Last Update Posted (Estimate): December 2, 2016
• Last Update Submitted That Met QC Criteria: December 1, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Histone Deacetylase Inhibitors; Docetaxel; Vorinostat
• Other Study ID Numbers: UMCC 2006.026