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

This study has been terminated.
(closed due to toxicity)
Sponsor:
Information provided by:
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00565227
First received: November 27, 2007
Last updated: January 14, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Non-small Cell Lung, Prostate, Bladder/Urothelial Cancers.
Drug: vorinostat (suberoylanilide hydroxamic acid)
Drug: docetaxel
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Suberoylanilide Hydroxamic Acid (Vorinostat) (NSC 701852) in Combination With Docetaxel in Patients With Advanced and Relapsed Solid Malignancies

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • The TITE-CRM dose escalation scheme will be used in this study to determine the maximum tolerated dose (MTD) of the combination therapy. [ Time Frame: 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%. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Although response is not the primary endpoint of this trial, patients with measurable disease will be assessed by standard criteria. [ Time Frame: For the purposes of this study, tumor response will be assessed every 6 weeks. ] [ Designated as safety issue: Yes ]
  • To evaluate the blood levels of vorinostat and docetaxel when administered in combination. [ Time Frame: All blood levels of the drugs will be conducted during the first cycle of chemotherapy only. ] [ Designated as safety issue: Yes ]

Enrollment: 12
Study Start Date: April 2007
Study Completion Date: September 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    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 Name: 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 Name: Taxotere
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565227

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Deborah Bradley, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Dr. Deborah Bradley, University of Michigan Health Systems
ClinicalTrials.gov Identifier: NCT00565227     History of Changes
Other Study ID Numbers: UMCC 2006.026
Study First Received: November 27, 2007
Last Updated: January 14, 2010
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Docetaxel
Vorinostat
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 30, 2014