Taxoprexin Plus Carboplatin Treatment for Advanced Lung Cancer

A Phase III, Randomized, Study of Weekly Taxoprexin Plus Carboplatin Versus Paclitaxel Plus Carboplatin as First Line Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer

The primary objective of this trial is to compare the survival of patients with advanced non-small cell lung cancer (NSCLC) treated with weekly Taxoprexin in combination with carboplatin to those treated with paclitaxel plus carboplatin in a prospectively randomized trial. In addition, the response rate to each regimen, response duration, time to progression and time to treatment failure will be measured. Toxicity will be evaluated and compared between the two groups.

This is a randomized, multicenter, Phase III open-label study of weekly Taxoprexin® in combination with every three (3) week carboplatin compared to paclitaxel plus carboplatin every three (3) weeks, in patients with advanced non-small cell lung cancer (NSCLC) who have not received cytotoxic agents for advanced disease. Patients may have been previously treated with immunological agents. Patients will be randomized to receive Taxoprexin® at a dose of 400 mg/m2 intravenously by one (1)-hour weekly infusion, 5/6 weeks followed immediately by carboplatin AUC = 4 on weeks one (1) and four (4) as a 30 minute intravenous infusion or paclitaxel 225mg/m2 as a three (3) hour intravenous infusion followed immediately by carboplatin AUC = 6 as a 30 minute intravenous infusion, every three (3) weeks. Patients will receive Taxoprexin® and carboplatin infusions or paclitaxel and carboplatin infusions until progression of disease, intolerable toxicity, completion of six (6) treatment cycles of paclitaxel plus carboplatin or three (3) treatment cycles of Taxoprexin® plus carboplatin, refusal of continued treatment by the patient, or Investigator decision.

Inclusion Criteria:

1. Patients must have a histologic or cytologic diagnosis of non-small cell lung cancer. At the time of study entry, patients must have locally advanced (stage IIIb) or metastatic (stage IV) disease.
2. Patients must have at least one site of either measurable or non-measurable disease.
3. Patients must not have received prior systemic chemotherapy for metastatic disease. Prior adjuvant systemic chemotherapy is allowed. At least six (6) months must have elapsed since any prior adjuvant systemic chemotherapy.
4. At least 6 weeks (42 days) since any prior immunotherapy, cytokine, biologic, vaccine or other non chemotherapy anticancer systemic therapies, unless patients have progressed during or after such therapy.
5. At least 4 weeks (28 days) since any prior radiotherapy to > 25% of the bone marrow.
6. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
7. Patients must be at least 18 years of age.
8. Patients must have adequate hepatic and renal function.
9. Patients must have adequate bone marrow function.
10. Life expectancy of at least 3 months.
11. Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study and in keeping with the policies of their institution.

Exclusion Criteria:

1. Patients who have received prior systemic chemotherapy in the adjuvant setting with a treatment-free interval of less than six (6) months.
2. Patients who have a past or current history of neoplasms other than the entry diagnosis, except for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix and except for other cancers treated for cure and with a disease-free survival greater than 5 years.
3. Patients with symptomatic brain metastasis(es).
4. Women who are pregnant or nursing and men or women who are not practicing an acceptable method of birth control. Women may not breast-feed while on this study.
5. Patients with current active infections requiring anti-infectious treatment (e.g., antibiotics, antivirals, or antifungals).
6. Patients with current peripheral neuropathy of any etiology that is greater than grade 1.
7. Patients with unstable or serious concurrent medical conditions.
8. Patients with a known hypersensitivity to Cremophor.
9. Patients with Gilbert's syndrome.
10. Patients must not have had major surgery within the past 14 days.
11. Patients must not receive any concurrent chemotherapy, radiotherapy, or immunotherapy while on study.
12. No known HIV disease or infection.
13. Patients receiving ketoconazole, erythromycin, verapamil, diazepam, quinidine, or diltiazem.