A Study of Vorinostat in Patients With Solid Tumors (MK-0683-029)

NCT00127127 | Completed Phase 1 Results DMC

• 3 other identifiers: 0683-0292005_040MK-0683-029
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of this trial is to determine the maximum tolerated dose (MTD), or the maximum acceptable dose (MAD) and evaluate the dose limiting toxicity (DLT) of oral suberoylanilide hydroxamic acid in participants with solid tumors.

Conditions

Tumors

Keywords

Solid tumors

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced One or More Adverse Events

  An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to approximately 4 years

• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event

  An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to approximately 4 years

• Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1

  A DLT was defined as an event considered to be related to study treatment and included: 1) Grade 4 neutropenia refractory to treatments persisting more than 5 days; 2) Grade 3 or more severe neutropenic fever; 3) Grade 3 thrombocytopenia requiring blood transfusions or Grade 4 thrombocytopenia; 4) Grade 4 hemoglobin decrease; 5) Grade 3 or more severe non-hematological toxicities other than anorexia, nausea/vomiting, and fatigue. (For the diarrhea, it was defined as not to use the frequency for the grading. For the alanine aminotransferase \[ALT\]/aspartate aminotransferase \[AST\]), it was defined as the case of over 300 IU/L; 6) Grade 3 or more severe anorexia, nausea/vomiting, and fatigue refractory to treatments; and 7) compliance of the study drug, while administrating 14 consecutive days, was less than 50% due to the drug-related adverse experience.

  Up to 26 days

Secondary Outcomes (12)

• Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUC0-inf) of Vorinostat After a Single Oral Dose in a Fasted State

  Day 1: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

• AUC0-Inf of Vorinostat After a Single Oral Dose in a Fed State

  Day 3: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

• AUC0-inf of Vorinostat After 14 Days of Once-Daily or Twice-Daily Administration

  Day 19: pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

• Maximum Concentration (Cmax) of Vorinostat After a Single Oral Dose in a Fasted State

  Day 1: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

• Cmax of Vorinostat After a Single Oral Dose in a Fed State

  Day 3: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose

Study Arms (4)

Vorinostat 100 mg

EXPERIMENTAL

During Cycle 1, participants receive a single oral dose of vorinostat 100 mg on Day 1 in a fasted state, Day 3 in a fed state, and Day 19 in a fed state. On Days 5-18, participants receive vorinostat 100 mg twice daily, in the morning and evening. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle will be 26 days.)

Drug: vorinostat

Vorinostat 200 mg

EXPERIMENTAL

During Cycle 1, participants receive a single oral dose of vorinostat 200 mg on Day 1 in a fasted state; on Day 3 in a fed state; and on Day 19 in a fed state. On Days 5-18, participants receive vorinostat 200 mg twice daily, in the morning and evening. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle will be 26 days.)

Drug: vorinostat

Vorinostat 400 mg

EXPERIMENTAL

During Cycle 1, participants receive a single oral dose of vorinostat 400 mg on Day 1 in a fasted state; on Day 3 in a fed state; and on Day 19 in a fed state. On Days 5-18, participants receive a single oral dose of vorinostat 400 mg once-daily in the morning. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy during Cycle 2 and subsequent cycles. (Each cycle will be 26 days.)

Drug: vorinostat

Vorinostat 500 mg

EXPERIMENTAL

During Cycle 1, participants receive a single oral dose of vorinostat 500 mg on Day 1 in a fasted state; on Day 3 in a fed state; and on Day 19 in a fed state. On Days 5-18, participants receive a single oral dose of vorinostat 500 mg once-daily in the morning. If participants do not match to the discontinuation criteria, they can continue the same dose level therapy on the Cycle 2 and subsequent cycles.(Each cycle will be 26 days.)

Drug: vorinostat

Interventions

vorinostat DRUG

vorinostat 100 mg, 200 mg, 400 mg, or 500 mg single oral dose; once-daily or twice-daily administration

Also known as: MK-0683, L-001079038, suberoylanilide hydroxamic acid (SAHA)

Vorinostat 100 mg; Vorinostat 200 mg; Vorinostat 400 mg; Vorinostat 500 mg

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with histologically or cytologically diagnosed solid tumor; no standard therapy available or participant has failed to respond to standard therapy

You may not qualify if:

• Participants with history of immunotherapy, radiotherapy, surgery, or chemotherapy during the previous 4 weeks; previous treatment is 5 or more chemotherapeutic regimens.
• Any uncontrolled concomitant illness
• Are pregnant or breast-feeding
• Serious drug or food allergy

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Fujiwara Y, Yamamoto N, Yamada Y, Yamada K, Otsuki T, Kanazu S, Iwasa T, Hardwick JS, Tamura T. Phase I and pharmacokinetic study of vorinostat (suberoylanilide hydroxamic acid) in Japanese patients with solid tumors. Cancer Sci. 2009 Sep;100(9):1728-34. doi: 10.1111/j.1349-7006.2009.01237.x. Epub 2009 May 31.

  PMID: 19575752 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Vorinostat

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2005
• First Posted: August 5, 2005
• Study Start: June 10, 2005
• Primary Completion: August 21, 2009
• Study Completion: August 21, 2009
• Last Updated: September 13, 2022
• Results First Posted: May 2, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share