Valproic Acid With Chemoradiotherapy for Non-Small-Cell Lung Cancer

Valproic Acid in Combination With Concurrent Chemoradiotherapy Using Vinorelbine and Cisplatin for Inoperable Locally Advanced Non-Small-Cell Lung Cancer

This is non-randomized phase 2 study to evaluate toxicity and efficacy of VA with concurrent chemoradiotherapy (CCRT) containing weekly vinorelbine and cisplatin in patients with locally advanced inoperable non-small-cell lung cancer (NSCLC).All patients will be planned for three-dimensional conformal RT (3-DCRT). Concurrent weekly vinorelbine and cisplatin and oral valproic acid (VA)will be started at the first day of RT. Follow up will be conducted every 3 months after completion of the study treatment. Toxicity will be assessed using CTCAE, based on clinical examination and laboratory tests during the study treatment and at follow up visits. Response to treatment will be evaluated using RECIST criteria. Overall and progression free survival (OS and PFS) will be estimated using the Kaplan-Meier method.

Study Overview

• Status: Unknown
• Conditions: Locally Advanced Inoperable Non-small-lung Cancer
• Intervention / Treatment: Drug: Valproic acid

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Konstantin Lavrenkov, MD, PhD; Phone Number: 972-86400537; Email: constant@bgu.ac.il

Study Locations

• Israel
  • Beer Sheva, Israel, 84101
    • Recruiting
    • Soroka University Medical Center
    • Contact: Konstantin Lavrenkov, MD, PhD; Phone Number: +97286400537; Email: constant@bgu.ac.il
    • Sub-Investigator: Vladimir Gavrilov, MD, PhD
    • Contact: Julia Dudnik, MD; Phone Number: +97286400537; Email: juliad@clalit.org.il
    • Sub-Investigator: Julia Dudnik, MD
    • Sub-Investigator: Kerenr Rouvinov, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18 years.
2. Newly-diagnosed, histologically or cytologically confirmed NSCLC.
3. Inoperable stage IIIA-B disease
4. KPS > 60
5. FEV1 >1.2L
6. No previous RT to chest
7. No serious comorbid condition
8. No treatment with biological response modifiers or cytotoxic agents within four weeks prior to study entry
9. No participation in clinical trial using any investigational drug or device within four weeks prior to study entry
10. No serious complication of malignant condition
11. No previous or concurrent malignancy at other sites except cone biopsied in situ carcinoma of the uterine cervix and adequately treated basal cell or squamous cell carcinoma of the skin

12. Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

    Hemoglobin > 9.0 Gm/dL WBC count > 4.0x109/L Neutrophile count > 1.5 cells x 109/L, Version 1, May 12, 2010 Platelet count > 100 x 109/L, Creatinine < 1.5 mg/dL Total bilirubin < upper limit of normal (ULN) AST/SGOT < ULN Calcium < ULN

13. Ability to sign informed consent
14. Ability to attend follow-up visits

Exclusion Criteria:

1. Operable disease
2. Metastases to contra-lateral mediastinal lymph nodes
3. Distant metastases
4. KPS < 60
5. FEV1 < 1.2L
6. Previous RT to chest
7. Treatment with biological response modifiers or cytotoxic agents within four weeks prior to study entry
8. Participation in clinical trial using any investigational drug or device within four weeks prior to study entry
9. Major surgical procedure within two weeks prior to study entry
10. Serious comorbid condition, inclusive but not limited to myocardial infarction within previous six months, uncontrolled cardiac arrhythmias, uncontrolled angina pectoris, active infection including acute hepatitis
11. Serious complication of malignant condition
12. Previous or concurrent malignancy

13. Inadequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry:

    Hemoglobin < 9.0 Gm/dL WBC count < 4.0x109/L Neutrophile count < 1.5 cells x 109/L, Platelet count < 100 x 109/L, Creatinine > 1.5 mg/dL Total bilirubin > ULN (upper limit of normal) AST/SGOT > ULN Version 1, May 12, 2010 Calcium > ULN

14. Inability to sign informed consent
15. Psychological, familial, sociological or geographical conditions which do not permit regular medical follow-up and compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Valproic acid, Chemoradiotherapy	Drug: Valproic acid; 800mg per day for entire period of RT; Other Names: Sodium valproate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival	24 months

Collaborators and Investigators

• Sponsor: Soroka University Medical Center
• Investigators: Principal Investigator: Konstantin Lavrenkov, MD, PhD, Soroka University Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Anticipated): February 1, 2013
• Study Completion (Anticipated): February 1, 2015

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 16, 2010

Study Record Updates

• Last Update Posted (Estimate): March 29, 2011
• Last Update Submitted That Met QC Criteria: March 27, 2011
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Radiotherapy; Chemotherapy; Valproic acid; Non-small-cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid
• Other Study ID Numbers: SOR507910CTIL