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.
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
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.
Dose-limiting toxicities and maximum tolerated dose
Pharmacology and pharmacokinetics
Secondary outcomes (2)
Acetylation of histones in peripheral blood
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.
- First posted27 Jan 2003 (estimated)
- Study startMar 2001
- Primary completionApr 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Shivaani Kummar, MD, Principal investigator, NCI - Medical Oncology Branch
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.
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275, in Refractory Solid Tumors and Lymphomas
- ClinicalTrials.gov ID
- NCT00020579
- Acronym / sponsor ID
- 010124
- Conditions
- Cancer
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2001
- Primary completion
- Apr 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| entinostat | Drug | – |
Primary outcome
Dose-limiting toxicities and maximum tolerated dose
Pharmacology and pharmacokinetics
2 secondary outcomes
Acetylation of histones in peripheral blood
Tumor response by CT scan every 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2012.
- Results publicationRyan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shivaani Kummar, MD principal investigator
NCI - Medical Oncology Branch
3 sites in 1 country: see every site and its status.
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.