Study of Weekly Paclitaxel, Carboplatin and Irinotecan to Treat Lung Cancer

Phase II Study of Weekly Paclitaxel, Carboplatin and Irinotecan in Patients With Advanced Non-Small Cell Lung Cancer Nad Malignant Pleural Effusion

Evaluate the efficacy and toxicity of the weekly combination chemotherapy of Paclitaxel, Carboplatin and Irinotecan in Stage IIIb and IV NSCLC with malignant pleural effusion

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Paclitaxel, Carboplatin and Irinotecan

Detailed Description

Lung cancer is the leading cancer death in many countries of the world including Singapore. Non-small cell lung cancer (NSCLC) consists of 80-85% of lung cancers, and is a major health problem. The main etiology of lung cancer is well recognized and established to be cigarette smoking which accounts for up to 80% of the cases in the western countries. Due to success of anti-smoking campaign, we anticipate to see less smoking related lung cancer and more non-smoking related lung cancer which is rising rapidly. For eg, currently in Singapore, smoking only accounts for 50-60% of all lung cancers, this is particularly true in female patients, as smoking occured in 30-40% of female lung cancer patients only.

It is unclear if there is any significant difference in the fundamental biology between smoking and non-smoking related lung cancers, particularly in areas of natural course of disease, genetic changes of tumor cells, clinical presentation, response to treatment or survival. These are potential aspects for further investigation.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 308433
    • Johns Hopkins Singapore International Medical Center

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:

• Histological or cytological diagnosis of non-small cell lung cancer.
• Malignant pleural effusion proven by cytological examination.
• Patient must have stage IIIB or IV disease with malignant pleural effusion.
• We plan to recruit 16 patients who have smoked cigarettes of at least 20 pack per year, 16 patients who do not smoke but have been exposed to second hand smoking by living with a person who has smoked 20 pack per year cigarette in the same household and 16 patients who are non-smokers (never smoked) and no second hand smoking exposure in the same household. The accrual will be stopped once the number of patients is reached in each group.
• ECOG PS 0, 1 or 2.
• Measurable disease (in addition to malignant pleural effusion).
• No prior chemotherapy for metastatic or recurrent disease. Patient may have surgery or radiation or combined chemoradiation, or neoadjuvant chemotherapy at primary diagnosis. This kind of chemotherapy will not be counted as patient has had prior chemotherapy for metastatic or recurrent NSCLC.
• WBC > 3500/uL and ANC > 2,000/uL, platelet > 100,000/uL AST/ALT < 3 X UNL, bilirubin < 1.5 mg/dL ( or < 35 uM), creatinine < 1.5 mg/dL (or < 125uM for men and 90uM for women).
• Age > 18
• No history of congestive heart failure, myocardial infarction or life-threatening arrhythmia (such as ventricular tachycardia, supraventricular tachycardia, brachycardia < 40/min or atrial fibrillation or flutter with ventricular rate > 150/min) within 6 months of entry.
• Signed informed consent
• Negative mammogram and ovaries examination by CT scans and no history of breast cancer or ovarian cancer in female patients.
• Negative pregnancy test in female menstruating patient within one week of starting chemotherapy and use of effective contraceptive methods during study.
• Patients with brain metastasis will be eligible provided their neurological abnormality is stable or improved after whole brain radiation, stereostatic radiosurgery or gamma knife treatment and/or dexamethasone for 3 weeks and patients fulfil all other eligibility criteria.

Exclusion Criteria:

• ECOG performance status 3 or worse.
• Any prior chemotherapy regimen for metastatic or recurrent diseases.
• No measurable disease, even after drainage of pleural effusion.
• ANC < 1,999/uL or Bilirubin > 1.5 mg/dL (or > 35uM)
• Plt < 100,000/uL or
• ALT/AST > 3 x UNL
• Creatinine > 1.5mg/dL (or > 125uM)

Patient has history of congestive heart failure, myocardial infarction or life-threatening arrhythmia (such as ventricular tachycardia, supraventricular tachycardia, atrial fibrillation/flutter with ventricular rate > 150/min or bradycardia < 40/min) within 6 months before entry.

Prior history of breast cancer or ovarian cancer in female patients or any cancer except cured cervical carcinoma in-situ or skin cancer.

Fasting blood sugar > 200 mg/dL (> 14uM) except in patients on dexamethasone for brain metastases.

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: Paclitaxel, Carboplatin and Irinotecan; Study of Weekly Paclitaxel, Carboplatin and Irinotecan in patients with Non-Small Cell Lung Carcinoma	Drug: Paclitaxel, Carboplatin and Irinotecan; Paclitaxel-60mg/m2 weekly for 3 weeks Carboplatin - AUC 1.5, weekly for 3 weeks Irinotecan - 60mg/m2, weekly for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the efficacy and toxicity of the weekly combination chemotherapy of paclitaxel, carboplatin and irinotecan in Stage IIIB and IV NSCLC patients with malignant pleural effusion	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the pharmacokinetics and pharmacodynamics of paclitaxel and irinotecan in the blood and pleural effusion.	3 years
To compare the gene expression pattern of non-small cell lung cancer from cigarette-smoking, passive smoking and no tobacco exposure patients before and after chemotherapy.	3 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Alex Chang, MD, Johns Hopkins Singapore

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 23, 2007
• First Submitted That Met QC Criteria: April 23, 2007
• First Posted (Estimate): April 25, 2007

Study Record Updates

• Last Update Posted (Actual): February 11, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: lung cancer with malignant pleural effusion
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Pleural Effusion; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Paclitaxel; Irinotecan
• Other Study ID Numbers: JS 0312; NA_00037282 (Other Identifier: JHM IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No