Adult Grade III Lymphomatoid GranulomatosisPhase 1NCT00098891
MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas
A Phase 1 study testing entinostat and isotretinoin in people with Adult Grade III Lymphomatoid Granulomatosis and Anaplastic Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Grade III Lymphomatoid Granulomatosis, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma
- What is being tested?
- entinostat and isotretinoin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Mar 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
Who may be able to join
- Histologically confirmed solid tumor or lymphoma
- Metastatic, progressive, refractory, or unresectable disease
- Not amenable to standard curative measures
- No known brain metastases
- Performance status - ECOG 0-2
- More than 3 months
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- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- WBC ≥ 3,000/mm^3
- Hemoglobin > 9 g/dL
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- No suspected Gilbert's syndrome
- Creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No unstable cardiac arryhthmia
- Able to take and retain oral medications
- No malabsorption problems
- No acute or chronic gastrointestinal condition
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception 1 month before, during, and 3 months after study treatment
- No known HIV positivity
- No weight loss > 10% within the past 2 months
- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to MS-275 or isotretinoin
- No other uncontrolled illness
- No ongoing or active infection
- No seizure disorder
- No psychiatric illness or social situation that would preclude study participation
- More than 4 weeks since prior anticancer vaccine therapy
- More than 4 weeks since prior anticancer immunotherapy
- No concurrent anticancer vaccine therapy
- No concurrent anticancer immunotherapy
- More than 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas, mitomycin, or other agents known to cause prolonged marrow supression)
- No concurrent anticancer chemotherapy
- More than 4 weeks since prior anticancer hormonal therapy except gonadotropin-releasing hormone (GnRH) agonist therapy for non-castrated patients with prostate cancer
- Concurrent GnRH agonist therapy for non-castrated patients with prostate cancer allowed
- Concurrent luteinizing hormone-releasing hormone agonist therapy allowed provided there is evidence of tumor progression
- Concurrent adrenal steroid replacement therapy allowed
- No concurrent ketoconazole as second-line hormonal treatment for prostate cancer
- No concurrent corticosteroids except for treatment of refractory nausea or vomiting
- No other concurrent anticancer hormonal therapy
- More than 4 weeks since prior anticancer radiotherapy
- More than 2 weeks since prior palliative radiotherapy
- No concurrent anticancer radiotherapy
- More than 4 weeks since prior major surgery
- Recovered from all prior therapy
- No prior MS-275
- No prior oral isotretinoin
- Isotretinoin for the treatment of acne allowed provided > 3 years since prior administration
- More than 4 weeks since other prior anticancer therapy
- No concurrent tetracycline
- No concurrent high-dose vitamin A
- No concurrent valproic acid
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University
Baltimore, Maryland, 21287-8936
About this study
Official title: A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.
Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. MS-275 may increase the effectiveness of isotretinoin by making cancer cells more sensitive to the drug. MS-275 and isotretinoin may also stop the growth of solid tumors or lymphomas by stopping blood flow to the cancer. Combining MS-275 with isotretinoin may kill more cancer cells
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when administered with isotretinoin in patients with metastatic, progressive, refractory, or unresectable solid tumors or lymphomas.
SECONDARY OBJECTIVES:
- Determine, preliminarily, tumor response in patients treated with this regimen.
II. Determine the pharmacokinetic profile of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation study of MS-275.
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of MS-275 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients are treated at the MTD.
Patients are followed monthly.
- Conditions
- Adult Grade III Lymphomatoid Granulomatosis, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma
- Being tested
- entinostat, isotretinoin
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
entinostatDrug
Also called HDAC inhibitor SNDX-275, SNDX-275
Given orally
isotretinoinDrug
Also called 13-CRA, Amnesteem, Cistane, Claravis
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (entinostat, isotretinoin) | Experimental | Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Receives: Drug: entinostat; Drug: isotretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities defined as an adverse event which is likely related to the study medication
Graded using the CTCAE version 3.0.
Measured: 28 days
Maximum tolerated dose of entinostat and isotretinoin in combination
Measured: 28 days
Secondary outcomes (2)
Pharmacokinetics
Measured: Up to day 21 of course 2
Adverse events defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment
Graded using the CTCAE version 3.0. Summarized by dose level.
Measured: Up to 30 days after completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2004 (estimated)
- Study startOct 2004
- Primary completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Grade III Lymphomatoid GranulomatosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Roberto Pili, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098891
- Sponsor's protocol ID
- NCI-2012-02634
- Other IDs
- JHOC-J0438, U01CA070095, CDR0000396776
- Status last verified
- Jan 2013
- First submitted
- 8 Dec 2004
- Last updated
- 24 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2013. 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 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.
- ClinicalTrials.gov ID
- NCT00098891
- Acronym / sponsor ID
- NCI-2012-02634
- Conditions
- Adult Grade III Lymphomatoid Granulomatosis, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Oct 2004
- Primary completion
- Mar 2008 (actual)
- First posted
- 9 Dec 2004 (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.
Phase I trial to study the effectiveness of combining MS-275 with isotretinoin in treating patients who have metastatic or advanced solid tumors or lymphomas. MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Isotretinoin may help cancer cells develop into normal cells. MS-275 may increase the effectiveness of isotretinoin by making cancer cells more sensitive to the drug. MS-275 and isotretinoin may also stop the growth of solid tumors or lymphomas by stopping blood flow to the cancer. Combining MS-275 with isotretinoin may kill more cancer cells
Detailed description
PRIMARY OBJECTIVES:
- Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when administered with isotretinoin in patients with metastatic, progressive, refractory, or unresectable solid tumors or lymphomas.
SECONDARY OBJECTIVES:
- Determine, preliminarily, tumor response in patients treated with this regimen.
II. Determine the pharmacokinetic profile of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation study of MS-275.
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of MS-275 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients are treated at the MTD.
Patients are followed monthly.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (entinostat, isotretinoin) | Experimental | Drug: entinostat, Drug: isotretinoinPatients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (58 listed)
- Histologically confirmed solid tumor or lymphoma
- No known brain metastases
- Performance status - ECOG 0-2
- More than 3 months
- Absolute neutrophil count ≥ 1,500/mm^3
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| entinostatAlso: HDAC inhibitor SNDX-275, SNDX-275Given orally | Drug | Treatment (entinostat, isotretinoin) |
| isotretinoinAlso: 13-CRA, Amnesteem, Cistane, ClaravisGiven orally | Drug | Treatment (entinostat, isotretinoin) |
Primary outcome
Dose limiting toxicities defined as an adverse event which is likely related to the study medication
Time frame: 28 days
Graded using the CTCAE version 3.0.
Maximum tolerated dose of entinostat and isotretinoin in combination
Time frame: 28 days
2 secondary outcomes
Pharmacokinetics
Time frame: Up to day 21 of course 2
Adverse events defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment
Time frame: Up to 30 days after completion of study treatment
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 24 Jan 2013.
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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.
Roberto Pili principal investigator
Johns Hopkins University
1 site 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 and isotretinoin in people with Adult Grade III Lymphomatoid Granulomatosis and Anaplastic Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site 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?
The sponsor lists 58 inclusion and 0 exclusion criteria. 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 24 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 defined as an adverse event which is likely related to the study medication (time frame: 28 days). 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?
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 24 Jan 2013.