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

Recruitment & Eligibility

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.

Exclusion Criteria

Not provided

Study & Design

Primary Outcome Measures

Name	Time	Method
Phase 1 - Maximum Tolerated Dose (MTD) of STI571	After cycle 1, day 22	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.
Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin	After cycle 1, day 22	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.
Phase II - Radiographic Response	After Cycle 6, approximately 18 weeks.	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.

Secondary Outcome Measures

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

Recruitment & Eligibility