Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Extensive-Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00057837
First received: April 7, 2003
Last updated: January 11, 2013
Last verified: January 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. It is not yet known which combination chemotherapy regimen is more effective in treating extensive-stage small cell lung cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have extensive-stage small cell lung cancer.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Biological: G-CSF
Drug: Cisplatin
Drug: Etoposide
Drug: Irinotecan
Drug: Topotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study: Sequencing Topoisomerase Inhibitors for Extensive Stage Small Cell Lung Cancer (SCLC): Topotecan Sequenced With Etoposide/Cisplatin, and Irinotecan/Cisplatin Sequenced With Etoposide

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST) [ Time Frame: Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry. ] [ Designated as safety issue: No ]

    Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

    Objective response = CR + PR



Secondary Outcome Measures:
  • Duration of Response [ Time Frame: Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry. ] [ Designated as safety issue: No ]
    Duration of response is defined as the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started.

  • Overall Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 1 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to death.


Enrollment: 140
Study Start Date: March 2004
Study Completion Date: August 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PET (Topotecan/Etoposide/Cisplatin/G-CSF)
Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.
Biological: G-CSF
G-CSF will be administered subcutaneously at a dose of 5 mcg/kg once a day starting on day 11 until WBC recovery > 10,000 dL.
Other Names:
  • Filgrastim
  • Neupogen
  • recombinant-rnethionyl human granulocyte-colony stimulating factor
  • granulocyte colony-stimulating factor
  • r-metHuG-CSF
Drug: Cisplatin
Arm PET: 20 mg/m2 IV on days 8, 9 and 10 of each cycle following Etoposide. Arm PIE: 20 mg/m2 IV on days 1 and 8 of each cycle following Irinotecan.
Other Names:
  • Platinol®
  • Cis-diaminedichloroplatinum
  • Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • NSC 119875
Drug: Etoposide
Arm PET: 70 mg/m2 IV over 60 minutes on days 8, 9 and 10 of each cycle. Arm PIE: 85 mg/m2 orally (divided into 2 doses, 12 hours apart) on day 3 and 10 of each cycle.
Other Names:
  • VP-16
  • VePesid
  • VP-16-213
  • EPEG
  • epipodophyllotoxin
  • NSC # 141540
Drug: Topotecan
Topotecan 0.75 mg/m2 IV over 30 minutes on days 1,2 and 3 of each cycle (Arm PET only).
Other Names:
  • Hycamtin®
  • Hycamptamine
  • SK&F 104864-A
  • Topotecan Formula AS
Experimental: PIE (Irinotecan/Cisplatin/Etoposide)
Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Drug: Cisplatin
Arm PET: 20 mg/m2 IV on days 8, 9 and 10 of each cycle following Etoposide. Arm PIE: 20 mg/m2 IV on days 1 and 8 of each cycle following Irinotecan.
Other Names:
  • Platinol®
  • Cis-diaminedichloroplatinum
  • Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
  • DDP
  • CDDP
  • DACP
  • NSC 119875
Drug: Etoposide
Arm PET: 70 mg/m2 IV over 60 minutes on days 8, 9 and 10 of each cycle. Arm PIE: 85 mg/m2 orally (divided into 2 doses, 12 hours apart) on day 3 and 10 of each cycle.
Other Names:
  • VP-16
  • VePesid
  • VP-16-213
  • EPEG
  • epipodophyllotoxin
  • NSC # 141540
Drug: Irinotecan
50 mg/m2 IV over 90 minutes on days 1 and 8 of each cycle (Arm PIE only).
Other Names:
  • Camptothecin-11
  • CPT-11

Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the response frequency of patients with extensive stage small cell lung cancer treated with topotecan, cisplatin, and etoposide and with irinotecan, cisplatin, and etoposide.
  • Evaluate the toxic effects of these regimens in these patients.
  • Evaluate the duration of response and survival of patients treated with these regimens.

Secondary

  • To investigate the occurrence of various breast cancer resistance protein (BCRP) alleles in patients receiving topoisomerase 1 inhibitors and their impact on clinical response and toxicity.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I (PET): Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.
  • Arm II (PIE): Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10.

In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

ACTUAL ACCRUAL: A total of 140 patients were accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Extensive stage small cell lung cancer (SCLC) with measurable disease, evaluated within 2 weeks prior to randomization
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
  • Disease-free for >=5 years if had a prior second malignancy other than treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
  • Adequate hematologic, hepatic and renal function determined by the following tests, within 4 weeks prior to randomization: white blood cell (WBC) >=4000/mm3 and platelets >=100,000/mm3; bilirubin <= upper limit of normal; serum glutamic pyruvate transaminase (SGPT) or alanine transaminase (ALT) and serum glutamic oxaloacetic transaminase (SGOT) or aspartate transaminase( AST) <=2.5 x upper limit of normal if no demonstrable liver metastases or <=5 times upper limit of normal in the presence of liver metastases; Calculated creatinine clearance >=30 using the formulas in the protocol
  • Age 18 and older
  • Strongly advised to use an accepted and effective method of contraception
  • Those with central nervous system (CNS) metastases were eligible if the metastases were treated without advancing symptoms prior to the initiation of chemotherapy
  • Those receiving erythropoietin could continue to receive it

EXCLUSION CRITERIA:

  • Prior radiotherapy for lung cancer; Prior radiotherapy allowed only for central nervous system (CNS) metastases
  • Prior chemotherapy for this disease
  • Pregnant or lactating
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00057837

  Show 79 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Joseph Aisner, MD Rutgers Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00057837     History of Changes
Other Study ID Numbers: CDR0000276590, U10CA021115, E5501
Study First Received: April 7, 2003
Results First Received: January 11, 2013
Last Updated: January 11, 2013
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
extensive stage small cell lung cancer
Topotecan
Etoposide
Cisplatin
Irinotecan

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Etoposide
Etoposide phosphate
Irinotecan
Lenograstim
Topoisomerase Inhibitors
Topotecan
Adjuvants, Immunologic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014