Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1)) - Full Text View

Sponsor:	Merck
Information provided by:	Merck
ClinicalTrials.gov Identifier:	NCT00111813

Purpose

The purposes of this study are:

To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma
To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.

Condition	Intervention	Phase
Multiple Myeloma	Drug: vorinostat Drug: bortezomib	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia hereditary multiple exostoses

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Suberoylanilide hydroxamic acid Bortezomib

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Mean Duration of Treatment With Vorinostat [ Time Frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months ] [ Designated as safety issue: Yes ]
Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity.

Progressive disease was defined as:
- >25% increase in the level of serum monoclonal paraprotein.
- 25% increase in 24-hour urinary light chain excretion.
- >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy.
- Development of new bone lesions or soft tissue plasmacytomas.
- Development of hypercalcemia.
Intolerable toxicity was based on the clinical judgment of the investigator.

Secondary Outcome Measures:

Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug [ Time Frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months ] [ Designated as safety issue: Yes ]
An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib [ Time Frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months ] [ Designated as safety issue: Yes ]
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
Clinical AE Summary [ Time Frame: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months) ] [ Designated as safety issue: Yes ]
An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.
Laboratory AE Summary [ Time Frame: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months ] [ Designated as safety issue: Yes ]
An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.

Enrollment:	34
Study Start Date:	September 2005
Study Completion Date:	May 2011
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: vorinostat 200 mg + bortezomib 0.7 mg/m^2 Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.	Drug: vorinostat Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break). Other Names: MK0683 Zolinza® Suberoylanilide Hydroxamic Acid (SAHA) Drug: bortezomib Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles. Other Name: Velcade
Experimental: vorinostat 200 mg + bortezomib 0.9 mg/m^2 Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.	Drug: vorinostat Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break). Other Names: MK0683 Zolinza® Suberoylanilide Hydroxamic Acid (SAHA) Drug: bortezomib Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles. Other Name: Velcade
Experimental: vorinostat 300 mg + bortezomib 1.3 mg/m^2 Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.	Drug: vorinostat Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break). Other Names: MK0683 Zolinza® Suberoylanilide Hydroxamic Acid (SAHA) Drug: bortezomib Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles. Other Name: Velcade
Experimental: vorinostat 400 mg + bortezomib 0.9 mg/m^2 Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.	Drug: vorinostat Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break). Other Names: MK0683 Zolinza® Suberoylanilide Hydroxamic Acid (SAHA) Drug: bortezomib Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles. Other Name: Velcade
Experimental: vorinostat 400 mg + bortezomib 1.1 mg/m^2 Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.	Drug: vorinostat Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break). Other Names: MK0683 Zolinza® Suberoylanilide Hydroxamic Acid (SAHA) Drug: bortezomib Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles. Other Name: Velcade
Experimental: vorinostat 400 mg + bortezomib 1.3 mg/m^2 Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.	Drug: vorinostat Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break). Other Names: MK0683 Zolinza® Suberoylanilide Hydroxamic Acid (SAHA) Drug: bortezomib Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles. Other Name: Velcade

Eligibility

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

Criteria

Inclusion Criteria:

Adults with refractory or relapsed multiple myeloma
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities)
Adequate bone marrow reserve
Adequate hepatic and renal function
Ability to swallow capsules
3 weeks or more since prior chemotherapy and have recovered from prior toxicities

Exclusion Criteria:

Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment
Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism
Participants with other active/uncontrolled clinically significant illness
Pregnant or nursing female participants
Participants who received bortezomib within 3 months of start of this trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00111813

Sponsors and Collaborators

Merck

Investigators

Study Director:

Medical Monitor

Merck

More Information

No publications provided

Responsible Party:	Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00111813 History of Changes
Other Study ID Numbers:	MK-0683-015, 2005_018
Study First Received:	May 25, 2005
Results First Received:	March 10, 2011
Last Updated:	June 21, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders

Immunoproliferative Disorders
Immune System Diseases
Vorinostat
Bortezomib
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protease Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012