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

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

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.

Study Overview

• Status: Completed
• Conditions: Extensive Stage Small Cell Lung Cancer
• Intervention / Treatment: Biological: G-CSF; Drug: Cisplatin; Drug: Etoposide; Drug: Topotecan; Drug: Irinotecan

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Tunnell Cancer Center at Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center - Miami
  • Georgia
    • Macon, Georgia, United States, 31208
      • Medical Center of Central Georgia
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Cancer Care Center
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Moline, Illinois, United States, 61265
      • Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
    • Moline, Illinois, United States, 61265
      • Hematology & Oncology Care
    • Olympia Fields, Illinois, United States, 60461
      • Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
    • Rockford, Illinois, United States, 61104-2315
      • Swedish-American Regional Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Lafayette, Indiana, United States, 47904
      • Clarian Arnett Cancer Care
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • South Bend, Indiana, United States, 46617
      • Saint Joseph Regional Medical Center
  • Iowa
    • Bettendorf, Iowa, United States, 52722
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, PA - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Elkton, Maryland, United States, 21921
      • Union Hospital Cancer Program at Union Hospital
    • Frederick, Maryland, United States, 21701
      • Frederick Memorial Hospital Regional Cancer Therapy Center
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Regional Cancer Center at Hunterdon Medical Center
    • Hackensack, New Jersey, United States, 07601
      • CCOP - Northern New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Cancer Institute of New Jersey at Hamilton
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
    • Voorhees, New Jersey, United States, 08043
      • Fox Chase Virtua Health Cancer Program at Virtua West Jersey
  • New York
    • Bronx, New York, United States, 10466
      • Our Lady of Mercy Medical Center Comprehensive Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Cleveland, Ohio, United States, 44106-5065
      • Case Comprehensive Cancer Center
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Dale and Frances Hughes Cancer Center at Pocono Medical Center
    • Lemoyne, Pennsylvania, United States, 17043
      • Central Pennsylvania Hematology and Medical Oncology Associates, PC
    • Paoli, Pennsylvania, United States, 19301-1792
      • Cancer Center of Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Reading, Pennsylvania, United States, 19612-6052
      • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital Cancer Center - Scranton
    • Scranton, Pennsylvania, United States, 18510
      • Hematology and Oncology Associates of Northeastern Pennsylvania
    • Upland, Pennsylvania, United States, 19013
      • Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Regional Cancer Center at Sacred Heart Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic - Indianhead Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; r-metHuG-CSF; Neupogen; granulocyte colony-stimulating factor; recombinant-rnethionyl human granulocyte-colony stimulating factor; 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: CDDP; Platinol; platinum; DDP; Platinol-AQ; Platinol®; DACP; cis-platinum; diaminedichloroplatinum; Cis-diaminedichloroplatinum; Cis-diaminedichloroplatinum (II); 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: EPEG; VP-16; VP-16-213; VePesid; 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: Hycamptamine; Hycamtin®; 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: CDDP; Platinol; platinum; DDP; Platinol-AQ; Platinol®; DACP; cis-platinum; diaminedichloroplatinum; Cis-diaminedichloroplatinum; Cis-diaminedichloroplatinum (II); 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: EPEG; VP-16; VP-16-213; VePesid; 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: CPT-11; Camptothecin-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST)	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	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	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.	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.
Overall Survival	Overall survival is defined as the time from randomization to death.	Assessed every 3 months for 2 years, then every 6 months for 1 years

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Joseph Aisner, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2004
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: April 7, 2003
• First Submitted That Met QC Criteria: April 8, 2003
• First Posted (Estimated): April 9, 2003

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: extensive stage small cell lung cancer; Cisplatin; Topotecan; Etoposide; Irinotecan
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Adjuvants, Immunologic; Keratolytic Agents; Topoisomerase I Inhibitors; Etoposide; Etoposide phosphate; Cisplatin; Podophyllotoxin; Irinotecan; Lenograstim; Topotecan; Camptothecin
• Other Study ID Numbers: CDR0000276590; U10CA021115 (U.S. NIH Grant/Contract); E5501 (Other Identifier: Eastern Cooperative Oncology Group (ECOG))