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

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

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.

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.