Combination Chemotherapy in Treating Patients With Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00004186
First received: January 21, 2000
Last updated: April 10, 2013
Last verified: April 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: etoposide
Drug: ifosfamide
Drug: topotecan hydrochloride
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IIA Study of Sequential Ifosfamide and Topotecan in Patients With Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Determine the maximum tolerated dose and dose limiting toxicity of topotecan when combined with ifosfamide in patients with limited or extensive stage small cell lung cancer [ Time Frame: from baseline up to 6 courses of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the pharmacokinetics of topotecan and correlate with toxicity or tumor response in these patients. [ Time Frame: from baseline up to 6 courses of treatment ] [ Designated as safety issue: Yes ]
  • Determine the effect of topotecan on apoptosis in tumor tissues and correlate the apoptosis-inducing effects with antitumor effects of topotecan in these patients. [ Time Frame: baseline through survival ] [ Designated as safety issue: No ]
  • the response rate, time to progression, and survival of chemotherapy naive limited or extensive stage small cell lung cancer patients treated with ifosfamide and topotecan and then crossover consolidation/salvage therapy [ Time Frame: baseline to survival ] [ Designated as safety issue: No ]
    Determine the response rate, time to progression, and survival of chemotherapy naive limited or extensive stage small cell lung cancer patients treated with ifosfamide and topotecan and then crossover consolidation/salvage therapy with carboplatin and etoposide.

  • Determine the response rate, time to progression, and survival of pretreated limited or extensive stage small cell lung cancer patients treated with ifosfamide and topotecan as salvage therapy [ Time Frame: baseline to survival ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: December 1996
Study Completion Date: December 2004
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicity of topotecan when combined with ifosfamide in patients with limited or extensive stage small cell lung cancer. II. Determine the pharmacokinetics of topotecan and correlate with toxicity or tumor response in these patients. III. Determine the effect of topotecan on apoptosis in tumor tissues and correlate the apoptosis-inducing effects with antitumor effects of topotecan in these patients. IV. Determine the response rate, time to progression, and survival of chemotherapy naive limited or extensive stage small cell lung cancer patients treated with ifosfamide and topotecan and then crossover consolidation/salvage therapy with carboplatin and etoposide. V. Determine the response rate, time to progression, and survival of pretreated limited or extensive stage small cell lung cancer patients treated with ifosfamide and topotecan as salvage therapy.

OUTLINE: This is a dose escalation study of topotecan (phase I). Patients are stratified by disease stage (extensive vs limited) and prior chemotherapy (naive vs pretreated) in phase II. Induction therapy: Patients receive topotecan IV over 72 hours and ifosfamide IV over 30 minutes every 3 weeks. Chemotherapy naive patients with complete or partial response after 3 courses, stable disease after 2 courses, or progressive disease at any time receive consolidation/salvage chemotherapy. Pretreated patients continue on induction regimen for a minimum of 6 courses unless disease progression or unacceptable toxicity. Phase I: Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicity. Salvage chemotherapy: Patients with extensive stage disease receive carboplatin IV over 30 minutes on day 1 and etoposide IV over 45 minutes on days 1, 2, and 3. Treatment repeats every 3 weeks for up to 4 to 6 courses. Patients with limited stage disease undergoing chest irradiation receive treatment every 28 days for the first course. Patients are followed every 2 months for 1 year, every 3 months for 1 year, and then every 4 months thereafter.

PROJECTED ACCRUAL: Approximately 15-20 patients will be accrued for phase I and approximately 35 patients will be accrued for phase II of this study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed limited or extensive stage small cell lung cancer Measurable or evaluable disease No uncontrolled brain metastases

PATIENT CHARACTERISTICS: Age: Not specified Performance status: ECOG 0-2 Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 2.0 mg/dL Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years, except: Nonmelanomatous skin cancer Carcinoma in situ of the cervix No significant active infection

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No more than 1 prior first line chemotherapy regimen Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy (except brain irradiation) Surgery: Recovered from recent surgery

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004186

Locations
United States, Alabama
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Study Chair: Francisco Robert, MD, FACP University of Alabama at Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00004186     History of Changes
Other Study ID Numbers: CDR0000067427, UAB-9626, UAB-F961125015, NCI-G99-1647
Study First Received: January 21, 2000
Last Updated: April 10, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Alabama at Birmingham:
limited stage small cell lung cancer
extensive stage small cell lung cancer
recurrent small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide
Isophosphamide mustard
Ifosfamide
Carboplatin
Topotecan
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014