Residual Hypermethylation in Early Stage Non-Small Cell Lung Cancer (NSCLC) As Part of Adjuvant Therapy and Preventive Strategy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01209520
First received: September 22, 2010
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

The trial investigates the feasibility and efficacy of targeting Non-Small Cell Lung Cancer (NSCLC) "driven" by epigenetic changes. The investigators study the impact of 5-azacitidine (Vidaza®, Celgene, Summit, NJ, USA) in combination with conventional cytotoxic chemotherapy in a sequential fashion. The study population consists of all NSCLC patients who undergo "curative" lung cancer resection and whose tumors harbor hypermethylation in any of the protocol-specific genes (samples will be banked for additional molecular testing including other 21 loci which have shown to be important in lung carcinogenesis.


Condition Intervention
Lung Cancer
Non Small Cell Lung Carcinoma
Hypermethylation
Drug: Cisplatin
Drug: Carboplatin
Drug: Paclitaxel
Drug: Vidaza
Procedure: Tumor Specimen for Methylation Analysis
Procedure: Blood Sample for Methylation Analysis
Drug: Vinorelbine
Drug: Docetaxel
Drug: Pemetrexed

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study Targeting Residual Hypermethylation in Early Stage Non-Small Cell Lung Cancer As Part of Adjuvant Therapy and Preventive Strategy

Resource links provided by NLM:


Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • To determine the presence of methylated tumor suppressor genes (TSGs) in the tumor tissue and/or serum of patients diagnosed with NSCLC. [ Time Frame: Prior to cycle 1, prior to cycle 3, prior to cycle 6, and every 4 months for the first 2 years post-completion of therapy ] [ Designated as safety issue: No ]
  • To measure the grade of demethylation induced by 5-azacitidine on specific TSGs by analyzing plasma DNA, and global demethylation by analyzing WBC DNA, and determine the duration of this effect [ Time Frame: Prior to cycle 1, prior to cycle 3, prior to cycle 6, and every 4 months for the first 2 years post-completion of therapy ] [ Designated as safety issue: No ]
    This value will be the difference between percentage of hypermethylation at baseline (tumor tissue/serum samples) minus percentage of hypermethylation found at: prior to cycle 1, prior to cycle 3, prior to cycle 6, and every 4 months for the first 2 years post-completion of therapy divided by the percentage of hypermethylation at baseline.


Secondary Outcome Measures:
  • To obtain preliminary data on methylation "pattern/profile" of silenced genes due to promoter hypermethylation once they have been treated with conventional cytotoxic chemotherapy followed by 5-azacitidine, a demethylating agent. [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    In the event of recurrence, methylation analysis (including gene identification and percentage of hypermethylation) will be performed and compared with original "pattern/profile" of gene methylation.


Estimated Enrollment: 20
Study Start Date: July 2009
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: Cisplatin
Patients will receive a total of 4 cycles of adjuvant chemotherapy (each cycle given every 21 days). Conventional chemotherapy will be selected at discretion of the treating physicians except on those cases in which pathologic diagnosis indicates non squamous NSCLC.
Other Names:
  • Platinol®,
  • cis-diamminedichloroplatinum
Drug: Carboplatin
Patients will receive a total of 4 cycles of adjuvant chemotherapy (each cycle given every 21 days). Conventional chemotherapy will be selected at discretion of the treating physicians except on those cases in which pathologic diagnosis indicates non squamous NSCLC.
Other Name: Paraplatin®
Drug: Paclitaxel
Patients will receive a total of 4 cycles of adjuvant chemotherapy (each cycle given every 21 days). Conventional chemotherapy will be selected at discretion of the treating physicians except on those cases in which pathologic diagnosis indicates non squamous NSCLC.
Other Name: Taxol
Drug: Vidaza
Patient will receive 5-azacitidine at a dose of 75 mg/m2 intravenously daily on day 1-5 every 28 days for 6 cycles
Other Name: 5-azacitidine
Procedure: Tumor Specimen for Methylation Analysis
Obtained from tissue of resected NSCLC tumor.
Procedure: Blood Sample for Methylation Analysis
Pre-Surgery, Post-Surgery, Post-Vidaza Therapy and during follow-up.
Drug: Vinorelbine
Patients will receive a total of 4 cycles of adjuvant chemotherapy (each cycle given every 21 days). Conventional chemotherapy will be selected at discretion of the treating physicians except on those cases in which pathologic diagnosis indicates non squamous NSCLC.
Other Name: Navelbine®
Drug: Docetaxel
Patients will receive a total of 4 cycles of adjuvant chemotherapy (each cycle given every 21 days). Conventional chemotherapy will be selected at discretion of the treating physicians except on those cases in which pathologic diagnosis indicates non squamous NSCLC.
Drug: Pemetrexed
Patients will receive a total of 4 cycles of adjuvant chemotherapy (each cycle given every 21 days). Conventional chemotherapy will be selected at discretion of the treating physicians except on those cases in which pathologic diagnosis indicates non squamous NSCLC.

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  Eligibility

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

Inclusion Criteria:

  • Patients must have a pathologic diagnosis of NSCLC.
  • Patients must have surgical resection for NSCLC (stage I-IIIA) and tumor specimen (ideally) and/or blood sample available for biological correlative studies.
  • Patient's tumor specimen and/or blood sample must show hypermethylation in at least one (1) of the following genes: DAPK, RASSF1A, CDKN2A (p16INK4a), GATA-4, GATA-5, SPARC, MGMT, APC, and hMLH1.
  • Patient's age must be 18 years or greater.
  • Patients must have adequate organ and marrow function prior to be enrolled into the trial, as defined below:

    • Absolute neutrophil count (ANC) > 1500/mm3
    • Platelets > 100,000/mm3
    • Hemoglobin > 8.0 g/dL (with packed red blood cell transfusion or use of erythropoietin stimulating agents allowed)
    • Serum creatinine < 2.0 mg/dl.
    • Total bilirubin < 2.0 mg/dl.
    • AST/ALT < 2 x the upper limits of institutional normal.
  • ECOG performance status of 0, 1, or 2.
  • Estimated survival of > 12 months.
  • Patients must be able to understand and agree to sign an IRB-approved informed consent form, including permission to draw blood sample for correlative studies during active treatment and follow-up.
  • Women of child-bearing potential and men must agree to use adequate contraceptive method (hormonal or barrier method of birth control) prior to study entry for the duration of study.
  • Women of childbearing potential must have a negative serum pregnancy test prior to start targeted therapy with 5-azacitidine.
  • Patients with HIV infection (but not AIDS) are eligible for this trial. Therefore, no HIV testing will be required.

Exclusion Criteria:

  • Patients who are not candidates for surgical resection.
  • Patients who have received radiation therapy.
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, breast DCIS adequately treated, or other cancer for which the subject has been disease-free ≥ 5 years.
  • Subjects should not have a significant history of cardiac disease (e.g., unstable angina, congestive heart failure, or uncontrolled arrhythmias).
  • Subjects must not have an uncontrolled seizure disorder, or active neurological disease.
  • Patients who have significant systemic infections including AIDS.
  • Pregnant and/or lactating women.
  • Known or suspected hypersensitivity to azacitidine or mannitol.
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical illnesses.
  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: NCT01209520

Locations
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami Sylvester Comprehensive Cancer Center
Investigators
Study Chair: Ikechukwu Akunyili, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01209520     History of Changes
Other Study ID Numbers: UMIAMI-20080779, SCCC-2008045
Study First Received: September 22, 2010
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:
Lung Cancer
Non-Small Cell Lung Carcinoma
NSCLC
Methylation Analysis
Hypermethylation
Targeted Genes
Tumorigenesis
Tumor Supressor Genes

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Azacitidine
Pemetrexed
Vinorelbine
Docetaxel
Cisplatin
Carboplatin
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 26, 2014