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

This study has been terminated.
(It was decided to close the study to further enrollment based on data from a similar study using ABT-751 and Pemetrexed that did not show efficacy.)
Sponsor:
Collaborator:
Abbott
Information provided by:
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00735878
First received: August 13, 2008
Last updated: April 29, 2009
Last verified: April 2009
  Purpose

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.


Condition Intervention Phase
Non Small Cell Lung Cancer
Advanced Lung Cancer
Drug: ABT-751 and Carboplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Pharmacokinetic and Pharmacodynamic Study of ABT-751 in Combination With Carboplatin in Patients With Advanced Lung Cancer

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • 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). [ Time Frame: This will be determined during the phase 1 portion of the study ] [ Designated as safety issue: Yes ]
  • To evaluate the efficacy of the combination with ABT-751 and carboplatin in patients with advanced NSCLC. [ Time Frame: This will be determined after enrollment is completed and data is analyzed ] [ Designated as safety issue: No ]
  • To determine the median survival in the study population [ Time Frame: from the start of the study until the last subject dies ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: this will be determined once enrollment is complete and the data is analyzed ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: this will be determined once enrollment is complete and the data is analyzed ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: September 2004
Study Completion Date: January 2009
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ABT-751 and Carboplatin
    This primary objective of this Phase 1/2 study is to evaluate the DLT and MTD of escalating oral doses of ABT-751 given BID on Day 1 of each cycle for 7 days in combination with carboplatin given on a 21-day schedule. The carboplatin dose is fixed at AUC 6 and will be administered on Day 4 during the first cycle to facilitate the pharmacokinetic analysis. During the subsequent cycles both agents will be administered on Day 1. ABT-751 is administered at the following dose levels using the Simon rapid dose escalation model: 100, mg, 125 mg, 150 mg, 175 mg and 200 mg BID.
    Other Name: Paraplatin
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ≥ 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 and ALT ≤ 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00735878

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Abbott
Investigators
Principal Investigator: Konstantin H Dragnev, MD Dartmouth-Hitchcock Medical Center
  More Information

No publications provided by Dartmouth-Hitchcock Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Konstantin H. Dragnev, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00735878     History of Changes
Other Study ID Numbers: D0412
Study First Received: August 13, 2008
Last Updated: April 29, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
Lung Cancer
Advanced Lung Cancer
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014