Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer Advanced Disease Untreated Ixabepilone Carboplatin Bevacizumab
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 82
Healthy volunteers: no

Brief summary:
This is a multicenter, non-randomized, Phase II study of patients with previously untreated NSCLC not amenable to radiotherapy or surgical treatment. The planned enrollment for this trial is 78 patients (including a 10% rate for inevaluable patients). There will be a total of 39 patients in each cohort (Cohorts A and B).

Detailed description:
The trial will include a lead-in phase for each cohort to assess safety. In Cohort A, 10 patients will receive ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle. If no unexpected toxicities occur, Cohort A will open to enrollment. Enrollment for Cohort A will be done in two stages (after the lead-in portion is completed). The first stage for Cohort A will enroll a total of 22 patients (this will include the 10 patients from the lead-in phase). If there are at least 3 responses during stage 1, enrollment for stage 2 will proceed. For stage 2 of the study, 17 additional patients will be enrolled (for a total of 39 patients in Cohort A). During stage 1 and stage 2, patients in Cohort A will receive treatment with ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day 1 of each 21-day treatment cycle. Treatment will continue until disease progression or unacceptable toxicity occurs.

After the lead-in phase for Cohort A is completed, a similar lead-in portion, also consisting of 10 patients, will be done for Cohort B. Patients in Cohort B will receive ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of one 21-day treatment cycle. If no unexpected toxicities occur in this group, Cohort B will open to enrollment. Enrollment for Cohort B will also be done in two stages (after the lead-in portion is completed). The first stage for Cohort B will enroll a total of 22 patients (this will include the 10 patients from the lead-in phase). If there are at least 3 responses during stage 1, enrollment for stage 2 will proceed. For stage 2 of the study, 17 additional patients will be enrolled (for a total of 39 patients in Cohort B). During stage 1 and stage 2, patients in Cohort B will receive treatment with ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of each 21-day treatment cycle. Treatment will continue until disease progression or unacceptable toxicity occurs.

Unexpected toxicities include any grade 4 hematologic toxicity or grade 3/4 non hematologic toxicity that does not reverse within 7 days in more than 2 patients.

Eligible patients will receive ixabepilone, carboplatin, and bevacizumab (bevacizumab will be administered to patients in Cohort B only) at 21-day intervals. Patients will be re evaluated every 6 weeks using computerized tomography (CT) scans. Response to therapy will be assigned using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse et al. 2000) (see Section 7). Patients who have objective response or stable disease will continue treatment for 6 cycles, until the time of tumor progression or intolerable treatment-related side effects. Patients in Cohort B without progressive disease will be eligible to receive bevacizumab monotherapy for 6 additional cycles, or until undue toxicity or tumor progression occurs.

Arms:
arm 1: ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle. arm 2: ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of one 21-day treatment cycle.

Interventions: intervention 1: Ixabepilone intervention 2: Carboplatin intervention 3: Bevacizumab
Intervention descriptions: intervention 1: ixabepilone 30 mg/m2 intervention 2: carboplatin AUC = 6 intravenously (IV) on Day 1 of one 21-day treatment cycle. intervention 3: bevacizumab 15 mg/kg on Day 1 of one 21-day treatment cycle.

Protocol document: