Pharmacokinetic & Pharmacodynamic Study of ABT-751 With Carboplatin in Patients With Advanced Lung Cancer

• Status: Terminated
• Trial end date: 2009-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objectives:

The primary objectives of this study are as follows:

• To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of escalating ABT-751 in combination with fixed dose carboplatin in patients with advanced non small cell lung cancer (NSCLC).

• To evaluate the efficacy of the combination with ABT-751 and carboplatin in patients with advanced NSCLC

• To determine the median survival in the study population

Secondary Objectives

The secondary objectives are:

• To characterize the pharmacokinetic profile of ABT-751 given in combination with carboplatin in a subset of patients, treated at the MTD or recommended doses for Phase 2.

• To determine the pharmacodynamics of ABT-751 as a single agent and the combination of ABT-751 and carboplatin as evaluated by cell cycle analysis of buccal mucosa cells.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dartmouth-Hitchcock Medical Center; Konstantin Dragnev
• Collaborator: Abbott
• Treatments: Carboplatin

Criteria

Inclusion Criteria:

1. At least 18 years of age.

2. Pathologically or cytologically confirmed diagnosis of NSCLC .

3. At least one measurable lesion (not amenable to resection) for Response Evaluation Criteria in Solid Tumors (RECIST) tumor assessments. Target lesions must not have been in the previous radiation port.

4. Advanced stage of disease (IIIB with malignant pleural effusion or Stage IV) with no known curative treatment that has progressed despite therapy for recurrent/metastatic disease or prior therapy was discontinued due to intolerable toxicities. During the phase II portion of the study, previously untreated patients with IIIB with malignant pleural effusion or Stage IV NSCLC may be enrolled.

5. For patients participating in the phase I part of the study, no alternative therapy is available that is expected to prolong overall or progression-free survival. Unacceptable toxicities during first- or second-line therapy or evidence for disease progression.

6. Adequate hematologic, renal and hepatic function as follows:

• Hematologic: ANC (absolute neutrophil count) ≥ 1200/mm3; Platelets; ≥ 100,000/mm3; hemoglobin: ≥ 8.5 g/dL;

• Renal function: serum creatinine ≤ 2.0 mg/dL; renal (CrCl > 50 ml/min by Jelliffe or Cockcroft Gault Formula),

• Hepatic function: Bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with liver metastases); AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 X the upper limits of normal (ULN) (≤ 5 X ULN for patients with liver metastases).

7. Adequate performance status, Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.

8. Prior platinum (cisplatin, carboplatin or oxaliplatin) therapy is allowed.

9. Patient or patient's legally acceptable representative has voluntarily signed and dated an informed consent form approved by an Institutional Review Board (IRB), prior to any study-specific procedures.

Exclusion Criteria:

1. Any other malignancy within 3 years except in situ carcinoma.

2. Untreated central nervous system (CNS) metastasis.

3. A greater than Grade 1 National Cancer Institute Common Toxicity Criteria (NCI CTC) neurology category findings at baseline.

4. Concurrent anti-cancer therapy or radiotherapy.

5. Concurrent therapy with colchicines.

6. Prior therapy with ABT-751.

7. Cytotoxic chemotherapy within 3 weeks of initiating investigational treatment.

8. Any investigational therapy within 4 weeks.

9. Female patients that are pregnant or breastfeeding.

10. Patients of childbearing potential (male and female) that do not agree to use a contraceptive method deemed acceptable by the investigator while in the study and for up to three months following completion of therapy.

11. Documented allergy or hypersensitivity to carboplatin or sulfa.

12. Patient has received more than 2 prior chemotherapy regimens for advanced disease. Adjuvant chemotherapy administered more than 6 months prior to enrollment does not count towards this limit.

13. Patient is classified as 3 or 4 by New York Heart Association (NYHA) Functional Classification, defined as:

• Class 3: Patients with marked limitation of physical activity, comfortable at rest, but less than ordinary activity causes symptoms.

• Class 4: Patients are unable to carry on any physical activity without symptoms and symptoms are present even at rest.

14. Evidence of clinically significant medical condition(s) that compromises safety, compliance, or study conduct, and/or is considered by the investigator to be unable to tolerate the proposed treatment or procedures.