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

NCT01209520 | Completed Results DMC

• 2 other identifiers: 20080779SCCC-2008045
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Cancer; Non Small Cell Lung Carcinoma; Hypermethylation

Keywords

Lung Cancer; Non-Small Cell Lung Carcinoma; NSCLC; Methylation Analysis; Hypermethylation; Targeted Genes; Tumorigenesis; Tumor Supressor Genes

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients Showing a Presence of Methylated Tumor Suppressor Genes in Their Tumor Tissue and/or Serum Achieving Partial or Complete Response to Protocol Therapy.

  To determine the feasibility and efficacy of incorporating a demethylating agent (5-azacitidine; Vidaza®, Celgene, Summit, NJ, USA) as part of adjuvant therapy in patients diagnosed with NSCLC who harbor methylated tumor supressor genes (TSGs) in their tumor tissue and/or serum. Response to be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.0.

  Up to 2 years

• Degree of Demethylation in Patient Tumor Tissue and/or Serum Induced by 5-azacitidine on Specific Tumor Specific Genes (TSGs)

  To measure the grade of demethylation induced by 5-azaciditine on specific TSGs by analyzing plasma DNA, and global demethylation by analyzing WBC DNA, and determine the duration of this effect.

  Up to 2 years

Study Arms (1)

Adjuvant Chemotherapy + Vidaza

EXPERIMENTAL

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

Interventions

Cisplatin DRUG

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.

Also known as: Platinol®,, cis-diamminedichloroplatinum

Adjuvant Chemotherapy + Vidaza

Carboplatin DRUG

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.

Also known as: Paraplatin®

Adjuvant Chemotherapy + Vidaza

Paclitaxel DRUG

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.

Also known as: Taxol

Adjuvant Chemotherapy + Vidaza

Vidaza DRUG

Patient will receive 5-azacitidine at a dose of 75 mg/m2 intravenously daily on day 1-5 every 28 days for 6 cycles

Also known as: 5-azacitidine

Adjuvant Chemotherapy + Vidaza

Tumor Specimen for Methylation Analysis PROCEDURE

Obtained from tissue of resected NSCLC tumor.

Adjuvant Chemotherapy + Vidaza

Blood Sample for Methylation Analysis PROCEDURE

Pre-Surgery, Post-Surgery, Post-Vidaza Therapy and during follow-up.

Adjuvant Chemotherapy + Vidaza

Vinorelbine DRUG

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.

Also known as: Navelbine®

Adjuvant Chemotherapy + Vidaza

Docetaxel DRUG

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.

Adjuvant Chemotherapy + Vidaza

Pemetrexed DRUG

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.

Adjuvant Chemotherapy + Vidaza

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinogenesis

Interventions

Cisplatin; Carboplatin; Paclitaxel; Azacitidine; Blood Specimen Collection; Vinorelbine; Docetaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Limitations and Caveats

Study data were not analyzed due to insufficient number of evaluable patients.

Results Point of Contact

• Title: Ikechukwu Akunyili MD
• Organization: University of Miami

IAkunyili@med.miami.edu

305-243-6626

Study Officials

• Ikechukwu Akunyili, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 27, 2010
• Study Start: July 1, 2009
• Primary Completion: December 1, 2013
• Last Updated: February 24, 2015
• Results First Posted: February 24, 2015

Record last verified: 2015-02

Locations

US (1)