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CancerPhase 1NCT00020579

MS-275 in Treating Patients With Advanced Solid Tumors or Lymphoma

A Phase 1 study testing entinostat in people with Cancer, run by National Institutes of Health Clinical Center (CC) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer
What is being tested?
entinostat
How many people
75 participants
Where
3 sitesUnited States
Study dates
Mar 2001to Oct 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignancy that is metastatic or unresectable and for which no effective standard curative or palliative therapy exists
  • Brain metastases allowed provided both of the following criteria are met:
  • Received treatment for the brain metastases
  • Stable for ≥ 6 months without steroids or antiseizure medications

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2 OR
  • Karnofsky 50-100%

Life expectancy:

  • More than 3 months

Hematopoietic:

  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN) (≤ 3 mg/dL for patients with Gilbert's syndrome)
  • AST/ALT no greater than 2.5 times ULN
  • Albumin at least 75% of lower limit of normal

Renal:

  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • Cardiac ejection fraction normal by MUGA
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Adequate oral intake
  • No weight loss of more than 10% of actual body weight within the past 2 months
  • No history of allergic reaction to compounds of similar chemical or biological composition to study drug
  • No other uncontrolled illness
  • No ongoing or active infection
  • No seizure disorder
  • No psychiatric illness or social situation that would preclude study compliance
  • No acute or chronic gastrointestinal conditions (e.g., peptic ulcer or colitis) within the past 2 months that would interfere with drug tolerance or absorption
  • Willing and able to self-administer and document doses of MS-275

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior anticancer vaccine therapy and recovered
  • No concurrent immunotherapy

Chemotherapy:

  • At least 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • At least 8 weeks since prior UCN-01 and recovered
  • No concurrent chemotherapy

Endocrine therapy:

  • At least 4 weeks since prior anticancer hormonal therapy (except gonadotropin-releasing hormone [GnRH] agonists) and recovered
  • Concurrent corticosteroids for physiological replacement, as antiemetic therapy, or for an ongoing condition allowed
  • Must be on a stable dose during the past 4 weeks
  • No concurrent anticancer hormonal therapy except GnRH agonists for noncastrated patients with prostate cancer

Radiotherapy:

  • At least 4 weeks since prior anticancer radiotherapy and recovered
  • No concurrent radiotherapy
  • Concurrent localized radiotherapy to a single lesion allowed if the patient achieves at least a partial response

Surgery:

  • At least 3 weeks since prior major surgery

Other:

  • No other concurrent investigational or commercial antineoplastic therapies

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • National Naval Medical Center

    Bethesda, Maryland, 20889-5000

  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

    Bethesda, Maryland, 20892-1182

  • NCI - Center for Cancer Research

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas

RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma.

Read the detailed description

OBJECTIVES:

  • Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 in patients with advanced solid tumors or lymphomas.
  • Determine the profile of adverse events, including changes in laboratory parameters, in patients treated with this drug.
  • Assess the pharmacology and pharmacokinetics of this drug in these patients.
  • Design MS-275 regimens with possibly more frequent dose administration based on the pharmacology of MS-275 using the schedule in this study.
  • Determine the antineoplastic activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral MS-275 once on day 1. Courses repeat every 2 weeks (every 2-week schedule). Alternatively, patients receive oral MS-275 once on days 1, 8, 15, and 22 (weekly schedule). Courses repeat every 6 weeks. Treatment for both schedules continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MS-275 on the every 2-week schedule until the maximum tolerated dose (MTD) is determined. Once the MTD for the every 2-week schedule is determined, patients receive treatment on the weekly schedule as above. The MTD is then determined for the weekly schedule. The MTD for both schedules is defined as the dose preceding that at which at least 2 of up to 6 patients experience dose-limiting toxicity. Once the MTD is determined for the weekly schedule, up to 3 additional patients are accrued to receive MS-275 at the MTD of the weekly schedule.

Disease status is assessed every 3 months.

PROJECTED ACCRUAL: A total of 50-75 patients will be accrued for this study.

Conditions
Cancer
Being tested
entinostat
Keywords
stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma
Medical subject headings
Neoplasms, Lymphoma, T-Cell, Cutaneous, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • entinostatDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicities and maximum tolerated dose

  2. Pharmacology and pharmacokinetics

Secondary outcomes (2)
  1. Acetylation of histones in peripheral blood

  2. Tumor response by CT scan every 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startMar 2001
  3. Primary completionApr 2008
  4. Study completionOct 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Masking
None (open label)
Enrolment
75 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00020579
Sponsor's protocol ID
010124
Other IDs
01-C-0124, NCI-2792, CDR0000068615
Status last verified
Mar 2012
First submitted
11 Jul 2001
Last updated
15 Mar 2012
Results posted
No

Publications

  • Ryan QC, Headlee D, Sparreboom A, et al.: A phase I trial of an oral histone deacetylase inhibitor, MS-275, in advanced solid tumor and lymphoma patients. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-802, 2003.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing entinostat in people with Cancer, run by National Institutes of Health Clinical Center (CC) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities and maximum tolerated dose. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00020579, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2012; AzTrials last refreshed its copy on 2 Nov 2026.

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