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Azacitidine in Treating Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01281124
First received: January 20, 2011
Last updated: April 22, 2014
Last verified: December 2013
  Purpose

This phase II clinical trial is studying how well azacitidine works in treating patients with previously treated advanced non-small cell lung cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Other: diagnostic laboratory biomarker analysis
Other: pharmacological study
Drug: azacitidine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Phase II Study of 5-Azacytidine in Previously Treated Patients With Advanced NSCLC

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • DNA Hypomethylation and Re-expression of Silenced Tumor Suppressor Genes When Stratified for Low or High Expression of mir29 [ Time Frame: Up to 12 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    The change in mean methylation of the genes between the patients with a low mir29 and a high mir29 expression will be evaluated by a two-sample t-test. Secondary analyses include a multivariate regression where all 5 changes in methylation will be regressed on mir29 expression (low vs. high) and adjusted for patient demographic and clinical attributes at baseline.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From the day of initial treatment until death (from any cause), assessed up to 12 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Analyzed using a Kaplan-Meier methods.

  • Progression-free Survival [ Time Frame: From the day of initial treatment until documented disease progression (per PET) or death, assessed up to 12 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Analyzed using a Kaplan-Meier methods.


Enrollment: 1
Study Start Date: January 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (azacitidine)
Patients receive azacitidine subcutaneously on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: diagnostic laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Drug: azacitidine
Given subcutaneously
Other Names:
  • 5-AC
  • 5-azacytidine
  • azacytidine
  • Vidaza

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the ability of 5-azacytidine to cause DNA hypomethylation and re-expression of silenced tumor suppressor genes when stratified for high or low expression of mir29a, b, and c.

SECONDARY OBJECTIVES:

I. To compare the molecular studies (mir29 expression and tumor suppressor gene methylation) between archival tissue, fresh biopsy pre-treatment samples, and post-treatment fresh samples.

II. To determine the overall response rate by CT (RECIST 1.1 criteria) and PET (EORTC PET response criteria), PFS, and OS of patients treated with azacytidine in the second- or third-line setting.

III. To correlate the blood microRNA profiles (and changes in microRNA profiles) with response to azacytidine.

OUTLINE:

Patients receive azacitidine subcutaneously on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tissue and blood sample collection at baseline and periodically during study treatment for correlative studies. After completion of study treatment, patients are followed up for 12 weeks.

  Eligibility

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

Inclusion Criteria:

  • Advanced (stage 4 or recurrent) NSCLC, not eligible for any curative intent treatment

    • Tumor must be histologically or cytologically confirmed
  • Measurable disease (as defined by RECIST criteria)
  • Patients may have up to two (and at least one) prior cytotoxic regimens in the metastatic setting

    • Prior adjuvant chemotherapy following resection or definitive chemo-radiation for patients with locally advanced disease is not included in this
    • Allowable systemic therapy in the metastatic setting includes 2 cytotoxic regimens and erlotinib and/or other non-cytotoxic drugs (i.e., erlotinib, sorafenib, and other tyrosine kinase inhibitors do not count as a "cytotoxic regimen")
    • Prior adjuvant therapy or definitive chemo-radiation is allowed if completed > six months before the onset of "first-line" therapy in the metastatic setting - in this setting, adjuvant or definitive chemo-radiation will not "count" as one of the two cytotoxic regimens; if however, the patient relapses within six months from completion of adjuvant or definitive chemoradiation, then this therapy will be considered the first-line cytotoxic therapy
    • In the unusual circumstance where patients receive "adjuvant" therapy following resection of oligo-metastatic disease (for example brain metastasis and lung primary resections) and the treating physician decides to administer chemotherapy following all surgery, this will be considered "adjuvant" therapy and the same rules as noted above will apply for initiation of first-line systemic therapy
  • No patients with uncontrolled brain metastases or leptomeningeal disease

    • Patients with controlled brain metastases are allowed
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelets ≥ 100,000 x 10^9/L
  • Hemoglobin ≥ 9.0 gm/100 mL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance > 50 mL/min
  • No patients who are pregnant
  • Women of childbearing potential must have a negative pregnancy test
  • The patient must be willing to use adequate contraception for the duration of study treatment and up to four weeks following the last dose of drug
  • Archival diagnostic material sufficient for microRNA evaluation/assessment is preferred, though optional

    • The presence of archival material will not preclude the need for pre and post treatment biopsies
  • Willing to undergo biopsy pre-treatment and following first cycle

    • Biopsy may be from any accessible site (primary or metastatic)
  • No known HIV or hepatitis B or C (though testing for this is not required)
  • No uncontrolled intercurrent illness including, but not limited to:

    • Symptomatic CHF
    • Unstable angina pectoris
    • Serious cardiac arrhythmia
    • Serious infection
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • No patients who have significant psychiatric illness that, in the opinion of the principal investigator, would prevent adequate informed consent or render therapy unsafe
  • Patients may not have had a prior invasive malignancy except for adequately treated non-melanoma cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 2 years

    • For example, a stage 1 (T1c) prostate cancer 2 years prior to a diagnosis of NSCLC would not be exclusionary, however, a metastatic prostate cancer currently receiving hormonal or chemotherapy would be excluded
  • No other concurrent palliative radiotherapy
  • Recovered from prior surgery, radiation, or chemotherapy to ≤ grade 2 toxicity
  • Palliative radiation or surgical procedures (for example, endobronchial therapy) is allowed, but must have been completed > 2 weeks prior to starting treatment
  • No other investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy
  • No other concurrent investigational therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281124

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Gregory Otterson Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01281124     History of Changes
Other Study ID Numbers: NCI-2011-02570, NCI-2011-02570, OSU-10100, CDR0000692184, OSU 10100, 8617, P30CA016058, N01CM00070
Study First Received: January 20, 2011
Results First Received: May 15, 2013
Last Updated: April 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Azacitidine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014