Azacitidine and MS-275 in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer
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Purpose
This phase I/II trial is studying the side effects and best dose of azacitidine when given together with MS-275 and to see how well they work in treating patients with recurrent advanced non-small cell lung cancer. Azacitidine and MS-275 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with MS-275 may kill more tumor cells.
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Non-small Cell Lung Cancer Stage IIIA Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer |
Drug: entinostat Drug: azacitidine Other: pharmacological study |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I//II Study of Entinostat in Combination With 5-Azacytidine in Patients With Recurrent Advanced Non-Small Cell Lung Cancer |
- Maximum tolerated dose (MTD) of azacitidine when given together with entinostat, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 (phase I) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
- Objective response rate after treatment with azacitidine and entinostat using the Response Evaluation Criteria in Solid Tumors (RECIST) (phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 44 |
| Study Start Date: | August 2006 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Phase I: Patients receive azacitidine subcutaneously on days 1-6 and 8-10 and oral MS-275 on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of azacitidine 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. Phase II: Patients receive azacitidine as in phase I at the MTD determined in phase I and MS-275 as in phase I. |
Drug: entinostat
Given orally
Other Names:
Drug: azacitidine
Given subcutaneously
Other Names:
Other: pharmacological study
Correlative study
Other Name: pharmacological studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of azacitidine when given together with MS-275 in patients with recurrent advanced non-small cell lung cancer. (Phase I) II. Determine the safety and toxicity of this regimen in these patients. (Phase I) III. Determine the objective response rate in patients treated with this regimen. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetic profile of azacitidine and MS-275 in these patients.
II. Assess the pharmacodynamic effects of azacitidine and MS-275 on DNA methylation, histone acetylation, and gene re-expression by blood and sputum analysis (and tissue biopsies from select patients).
III. Assess the effect of azacitidine and MS-275 on progression-free survival and overall survival of these patients.
OUTLINE: This is a multicenter, phase I, dose-escalation study of azacitidine followed by an open-label, phase II study.
PHASE I: Patients receive azacitidine subcutaneously on days 1-6 and 8-10 and oral MS-275 on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of azacitidine 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.
PHASE II: Patients receive azacitidine as in phase I at the MTD determined in phase I and MS-275 as in phase I.
Patients undergo plasma sample collection for pharmacokinetic evaluation before beginning treatment and then at days 1, 10, and 17. Patients also undergo blood and sputum collection to evaluate the pharmacodynamic effects of azacitidine and MS-275 on DNA methylation before beginning treatment and then at days 10 and 29.
After completion of study treatment, patients are followed periodically for 4 weeks.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria:
Histologically or cytologically confirmed non-small cell lung cancer:
- Metastatic or unresectable disease
- Must have failed >= 1 prior chemotherapy regimen
- Measurable disease defined as >= 1 unidimensionally measurable lesion (longest diameter) >= 20 mm by conventional techniques or 10 mm by spiral CT scan
- No liver metastases that replace > 30% of the liver parenchyma
No uncontrolled brain metastases:
- Patients with brain metastases must have stable neurologic status after local therapy (e.g., surgery or radiotherapy) for >= 4 weeks with no neurologic dysfunction that would preclude evaluation of neurologic and other adverse events
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 12 weeks
- Platelet count >= 100,000/mm^3
- WBC >= 3,000/mm^3
- Absolute neutrophil count >= 1,500/mm^3
- AST and ALT =< 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance >= 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MS-275, azacitidine, mannitol, or other agents used in the study
- Recovered from all prior therapy-related toxicities
- No uncontrolled illness including, but not limited to, any of the following:
Ongoing or active infection; Symptomatic congestive heart failure; Unstable angina pectoris; Cardiac arrhythmia; Psychiatric illness or social situation that would preclude study treatment
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
- No concurrent radiotherapy, including palliative radiotherapy
- No concurrent valproic acid
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies, including chemotherapy
- Bilirubin normal
Contacts and Locations| United States, California | |
| USC Norris Comprehensive Cancer Center | Recruiting |
| Los Angeles, California, United States, 90033 | |
| Contact: Barbara J. Gitlitz 323-865-0451 gitlitz@usc.edu | |
| Principal Investigator: Barbara J. Gitlitz | |
| United States, Maryland | |
| Johns Hopkins University | Recruiting |
| Baltimore, Maryland, United States, 21287-8936 | |
| Contact: Charles M. Rudin 410-502-6078 rudin@jhmi.edu | |
| Principal Investigator: Charles M. Rudin | |
| United States, Texas | |
| M D Anderson Cancer Center | Active, not recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Charles Rudin | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00387465 History of Changes |
| Other Study ID Numbers: | NCI-2009-00220, J0658, CDR0000504083, U01CA070095 |
| Study First Received: | October 12, 2006 |
| Last Updated: | April 9, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases |
Azacitidine Histone Deacetylase Inhibitors Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013