Maximum Tolerated Dose, Safety and Efficacy of Docetaxel / Cisplatin + STI571

Study Overview
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Brief Summary
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This is a Phase 1/Phase 2 study of STI571 combined with docetaxel and cisplatin for treatment of patients with recurrent and metastatic Non-Small Cell Lung Cancer (NSCLC). This research study has 2 parts to it. The first part (Phase 1) is called a dose-escalation. Not all subjects enrolled into this phase of the study will receive the same dose. The purpose of the dose-escalation is to determine the highest safe dose of STI571 that can be used in combination with docetaxel and cisplatin. That dose will be used in Phase 2.

Official Title
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A Phase I - II Open Label Study of the Maximum Tolerated Dose, Safety and Efficacy of Docetaxel and Cisplatin Plus STI571 in Advanced Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Docetaxel, Cisplatin and STI571
* Drug: Docetaxel
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically recurrent, or advanced NSCLC: Stage IV disease; or Stage IIIB due to malignant pleural effusion is allowed- only if successfully pleurodesed. Tumor tissue slides must express phosophorylated pdgf-rB by IHC. At least one measurable target lesion as defined by RECIST criteria that has not been irradiated. No prior chemotherapy treatment for this disease will be allowed. Patients with brain metastasis will have to be, after appropriate treatment, neurologically stable for at least 1-2 weeks (off steroids) prior to study enrollment. ECOG performance status 0-1. Meets initial laboratory parameters. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Exclusion Criteria Any prior treatment with a biologic response modifier or chemotherapeutic agent for this disease. Any concomitant malignancy except non-melanoma skin cancer or in-situ carcinoma of the cervix. History of allergic reactions attributed to compounds of similar chemical or biologic composition to STI571 and/or docetaxel, or other drugs formulated with polysorbate 80 and/or cisplatin. Patients with: Contrast allergy. GI bleed ≤ 1 month from study enrollment. Intermittent or chronic oxygen requirements. Pulse oximetry <90%. Grade 3 dyspnea. History of poorly regulated anticoagulation with warfarin. Edema or fluid retention grade >1. Neuropathy grade ≥1. Uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, ≤3 months myocardial infarction or cardiac arrhythmia. Psychiatric illness/social situations that would limit compliance with study requirement or that would prevent informed consent or psychiatric illness/social situations requiring inpatient treatment within the past 3 months. Any type of hearing impairment. Known HIV infection. Receiving other investigational agents.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Docetaxel, Cisplatin and STI571|Treatment will consist of docetaxel plus cisplatin IV every 21days and oral STI571 given on Days -5 to 2 with each chemotherapy cycle. A maximum of 6 cycles will be given. Phase 1 dose levels are: Level 1 Docetaxel/Cisplatin 60 mg/m2, STI571 300mg Level 2 Docetaxel/Cisplatin 60 mg/m2, STI571 400mg Level 3 Docetaxel/Cisplatin 70 mg/m2, STI571 400mg Level 4 Docetaxel/Cisplatin 70 mg/m2, STI571 600mg Level 5 Docetaxel/Cisplatin 75 mg/m2, STI571 600mg Level 6 Docetaxel/Cisplatin 75 mg/m2, STI571 800mg Once the MTD level has been established, the previous dose level will be the dosing schedule for Phase II.|
|Drug: Docetaxel|nan|
|Drug: Cisplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - Maximum Tolerated Dose (MTD) of STI571 | To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin, when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC. | After cycle 1, day 22 | 
| Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin | To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC. | After cycle 1, day 22 | 
| Phase II - Radiographic Response | The percentage of patients with a complete or partial response. Responses for the Phase II portion of the trial will be by Response Evaluation Criteria In Solid Tumors (RECIST) criteria as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | After Cycle 6, approximately 18 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: 1 Year Survival | Phase II: Percentage of patients alive 1 year from the start of protocol treatment. | 1 year | 
| Change in Gd-MRI Measurement | The change in Gd-MRI perfusion/permeability measurement between pre and post 7-day of STI571 treatment. | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung cancer, non-small cell