Customizing First Line Chemotherapy in Advanced Non-Small Cell Lung Cancer (Customizing)

A Pilot Study of Customizing First Line Chemotherapy in Advanced Non-Small Cell Lung Cancer Based on Molecular Markers

The study aims at piloting the concept of customization of chemotherapy based on molecular markers in patients with stage IIIB (with pleural effusion) and IV with performance status ≤ 2 with pathologically proven non-small cell lung cancer (NSCLC). The study will not test or compare individual regimen but rather it will test the approach of customization concept as a whole.

The results of this pilot study will help in designing more definitive trials in our patient population.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Cisplatin, Gemzar, Docetaxel, Alimta

Detailed Description

The treatment of advanced NSCLC cancer includes various chemotherapies with equivalent regimens that have reached a therapeutic plateau. The selection of these regimens is completely empirical and physician dependent. Potential predictors of specific agent efficacy exist in the form of tumor molecular markers that are a reflection of the individual's genetic make up. Thus our study aims at utilizing these markers to more efficiently select the regimen in order to maximize the benefit to the patients rather than using empiric approaches. Fortunately, each of our selected regimens contains active and well-studied agents in the treatment of lung cancer (Table 1). This pilot study will help us determine the benefit, and safety of this approach (not individual regimen). The study is not to compare individual regimens but it aims at testing the whole concept of customization of chemotherapy based on molecular markers to help us in the future at selecting regimens based on these markers and not empirically. The results then will be used to determine more definitive future studies.

Furthermore, circulating tumor cells in the blood represent the future distant metastases that result in disease progression to incurable stages. The circulating tumor cells have the ability to cross into vessels, travel in circulation, and exit the vessels into tissues where they have the capability to grow. Therefore, these cells may express different biological and molecular features from the stationary cells in the primary tumors. Therefore, exploiting these circulating tumor cells for augmenting treatment approaches is of vital importance and utility.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Abdul Aziz Medical City for National Guard Health Affairs

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Microscopic diagnosis of NSCLC stages IIIB (with malignant pleural effusion) and IV
2. Having adequate tissue sample to perform the markers testing
3. Age ≥ 18 years
4. No prior chemotherapy treatment for lung cancer (Surgery and radiotherapy are acceptable)
5. No other concurrent cancer treatment
6. Performance status of 0- 2 per ECOG scale (Appendix II)

7. Adequate laboratory values as follows as follows:

   Absolute neutrophil count ≥ 1500/mm3 Platelet count ≥100, 000/ mm3 Total bilirubin ≤ 1.25X institutional upper normal level AST and ALT ≤ 3 X institutional upper normal level Serum creatinine ≤ 1.5 X institutional upper normal level

8. Presence of measurable disease

Exclusion Criteria:

1. Prior systemic treatment for lung cancer
2. History of hypersensitivity to drugs used
3. Diagnosis of other malignancy in the last 5 years excluding curatively treated non-melanoma skin cancer and in-situ cervical cancer
4. Medical illness that puts the patient at significant risk per investigator's discretion
5. Uncontrolled CNS disease. Patients with CNS metastatic disease treated with radiotherapy or surgery will be eligible if the CNS disease is stable 4 weeks after the treatment initiation without increase dose of steroids
6. Positive pregnancy test or refusal to use contraception during treatment. (Gynecology consultant for contraception)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cisplatin,Docetaxel,Gemzar, Premetrexed; Patients will receive treatment for up to six cycles of the assigned regimen unless there is disease progression or unacceptable toxicities. After treatment, the patients will be seen every 2 months for the first year, then every 3 months for the second year and every 6 months afterwards.	Drug: Cisplatin, Gemzar, Docetaxel, Alimta; Patients will be assigned to treatment according to the molecular biological results which will analyze excision repair cross-complementing (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and beta-tubulin genes in primary tumor cells which are present in tissues and peripheral blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy and Safety	Efficacy is measured by:overall response rate (partial response and complete response) using RECIST Criteriatime to disease progression (TTP)progression free survival (PFS)overall survival (OS); To evaluate the Number of participants with Adverse Events and Serious Adverse Events.Safety will include 5 parameters to be collected for all patients who receive the study regimen which are:Adverse EventsLaboratory AssessmentsVital SignsPhysical ExaminationsECG	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor marker	The molecular characteristics of circulating tumor cells harvested from peripheral blood; Correlation between the markers of circulating tumor cells and primary tumor.	3 years

Collaborators and Investigators

• Sponsor: National Guard Health Affairs
• Investigators: Principal Investigator: Abdulrahman Jazieh, MD/MPH, King Abdul Aziz Medical City for National Guard

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: March 19, 2011
• First Submitted That Met QC Criteria: May 18, 2011
• First Posted (Estimate): May 19, 2011

Study Record Updates

• Last Update Posted (Estimate): January 22, 2014
• Last Update Submitted That Met QC Criteria: January 19, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Cisplatin
• Other Study ID Numbers: RC09/095