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

NCT00735878 | Terminated Phase 1 Results DMC

• 1 other identifier: D0412
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non Small Cell Lung Cancer; Lung Cancer

Keywords

Lung Cancer; Advanced Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of ABT-751 in Combination With Carboplatin

  The maximum tolerated dose (MTD) of escalating ABT-751 in combination with fixed dose Carboplatin AUC 6 in patients with advanced non small cell lung cancer (NSCLC). Initially, 1 patient will be enrolled in dose level 1. If the patient experiences a Gr 2 toxicity, additional 2 patients will be enrolled at the dose level. If 1 of the 3 patients experience a Gr 3 toxicity or higher the cohort will be expanded to 6 patients. However, if 1 patient completes one cycle at the assigned dose regimen without a Gr 2 toxicity, enrollment in the next cohort (dose level 2) can begin. The rapid dose escalation scheme will apply to cohorts 1 through 3.

  21 Days (end of cycle 1)

• Objective Response Rate of Participants Using A Combination of ABT-751 and Carboplatin

  The effectiveness of the combination with ABT-751 and carboplatin in patients with advanced NSCLC as measured by objective response rate. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by CT or MRI: Complete Response (CR), The disappearance of all known disease determined by two observations not less than four weeks apart.; Partial Response (PR), At least a 30% or more decrease in total tumor load of the lesions that have been measured to determine the effect of therapy by two observations not less than four weeks apart.; Overall Response (OR) = CR + PR

  42 days (end of cycle 2)

• The Median Survival in the Study Population

  Median overall survival using the Kaplan Meier method

  from the start of the study until the last subject dies (up to 100 weeks)

Secondary Outcomes (2)

• Pharmacokinetic Profile of ABT-751 for Phase 2

  Randomization to maximum tolerated dose confirmed

• Number of Patients With Buccal Cells Demonstrating a Decline in Cyclin D1

  pretreatment (Day 0) and patient paired post- treatment (Days 4,8, 22) buccal swabs.

Study Arms (3)

ABT-751 100 mg and Carboplatin

EXPERIMENTAL

100 mg BID ABT-751 orally for 7 days. Carboplatin AUC 4.5 once every 21 days.

Drug: ABT-751 and Carboplatin

ABT-751 125 mg and Carboplatin

EXPERIMENTAL

125 mg BID ABT-751orally for 7 days. Carboplatin AUC 4.5 or 6 once every 21 days.

Drug: ABT-751 and Carboplatin

ABT-751 150 mg and Carboplatin

EXPERIMENTAL

150 mg BID ABT-751orally for 7 days. Carboplatin AUC 6 once every 21 days.

Drug: ABT-751 and Carboplatin

Interventions

ABT-751 and Carboplatin DRUG

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.

Also known as: Paraplatin

ABT-751 100 mg and Carboplatin; ABT-751 125 mg and Carboplatin; ABT-751 150 mg and Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• Pathologically or cytologically confirmed diagnosis of NSCLC .
• 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.
• 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.
• 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.
• 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).
• Adequate performance status, Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1.
• Prior platinum (cisplatin, carboplatin or oxaliplatin) therapy is allowed.
• 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.

You may not qualify if:

• Any other malignancy within 3 years except in situ carcinoma.
• Untreated central nervous system (CNS) metastasis.
• A greater than Grade 1 National Cancer Institute Common Toxicity Criteria (NCI CTC) neurology category findings at baseline.
• Concurrent anti-cancer therapy or radiotherapy.
• Concurrent therapy with colchicines.
• Prior therapy with ABT-751.
• Cytotoxic chemotherapy within 3 weeks of initiating investigational treatment.
• Any investigational therapy within 4 weeks.
• Female patients that are pregnant or breastfeeding.
• 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.
• Documented allergy or hypersensitivity to carboplatin or sulfa.
• 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.
• 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.

Sponsors & Collaborators

• Konstantin Dragnev: lead
• Abbott: collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (1)

• Ma T, Fuld AD, Rigas JR, Hagey AE, Gordon GB, Dmitrovsky E, Dragnev KH. A phase I trial and in vitro studies combining ABT-751 with carboplatin in previously treated non-small cell lung cancer patients. Chemotherapy. 2012;58(4):321-9. doi: 10.1159/000343165. Epub 2012 Nov 12.

  PMID: 23147218 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

ABT751; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Konstantin H. Dragnev, MD
• Organization: Dartmouth-Hitchcock Medical Center (DHMC)

konstantin.h.dragnev@hitchcock.org

(603) 650-6344

Study Officials

• Konstantin H Dragnev, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor Hematology/Oncology, Dept of Med

Study Record Dates

• First Submitted: August 13, 2008
• First Posted: August 15, 2008
• Study Start: September 1, 2004
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: October 12, 2018
• Results First Posted: October 12, 2018

Record last verified: 2018-10

Locations

US (1)