Cisplatin, Etoposide, and Cyclophosphamide in Treating Patients With Extensive-Stage Small Cell Lung Cancer

• Sponsor: Gundersen Lutheran Health System
• Information provided by (Responsible Party): Ronald Go, Gundersen Lutheran Health System

Study Description

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as cisplatin, etoposide, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin, etoposide, and cyclophosphamide together works in treating patients with extensive-stage small cell lung cancer.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: cisplatin; Drug: cyclophosphamide; Drug: etoposide	Phase 2

Detailed Description:

OBJECTIVES:

Primary

• Determine the safety of cisplatin, etoposide, and cyclophosphamide in patients with extensive stage small cell lung cancer.
• Determine the effect of this regimen on circulating endothelial cells in the peripheral blood of these patients.

Secondary

• Determine progression-free survival, tumor response rate, and overall survival in patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive cisplatin IV over 30 minutes-2 hours on day 1, etoposide IV over 1-2 hours on days 1-3 OR etoposide IV on day 1 and orally twice daily on days 2-3, and oral cyclophosphamide twice daily on days 8-19. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
• Maintenance therapy: Patients receive oral cyclophosphamide twice daily in the absence of disease progression.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	8 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Pilot Study of a Combination of Standard Etoposide/Cisplatin and Metronomic Cyclophosphamide in Patients With Newly Diagnosed Extensive Stage Small Cell Lung Cancer
Study Start Date :	June 2003
Actual Primary Completion Date :	May 2010
Actual Study Completion Date :	May 2010

Arms and Interventions

Arm

Intervention/treatment

Experimental: Oral cyclophosphamide plus standard cisplatin with etoposide; Etoposide 120 mg/m2 IV Days 1-3 or Etoposide 120 mg/ m2 IV Day1 followed by Etoposide 120 mg/ m2 PO BID Days 2-3; Cisplatin 60 mg/m2 IV Day 1 Every 21 days x 4 cycles; Cyclophosphamide 25 mg PO BID Days 8-19 of each cycle

Drug: cisplatin; 60 mg/m2 IV day 1, every 21 days for 4 cycles.; Drug: cyclophosphamide; 25 mg by mouth BID days 8-19 or each cycle x 4 cycles. After restaging (if no progression) maintenance cyclophosphamide alone 25 mg by mouth BID daily until disease progression; Other Name: Cytoxan; Drug: etoposide; 120 mg/m2 IV days 1-3 OR 120 mg/m2 IV day 1 and 120 mg/m2 by mouth BID days 2-3; Other Name: VP-16

Outcome Measures

Primary Outcome Measures :

1. Safety [ Time Frame: From time of registration to 30 days post treatment of last cycle. ]
2. Effect of metronomic chemotherapy on circulating endothelial cells [ Time Frame: Baseline to progression ]
   Collected cycle 1/day 1 of chemotherapy, Cycle 1/day 8, cycle 1/day 22, and then day 85 and 141, and at disease progression.

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: Registration to time of progression ]
2. Response rate [ Time Frame: From Registration to time of disease progression ]
3. Overall survival [ Time Frame: From registration to time patient expires ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

  • Extensive stage disease (i.e., disease beyond the hemithorax and cannot be encompassed safely by a tolerable radiation field)
• Measurable disease

• Concurrent CNS metastases allowed provided patient remains asymptomatic

  • Radiotherapy or surgery for uncontrolled symptoms allowed before study entry

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8 g/dL (transfusion allowed)

Hepatic

• ALT ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times ULN

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past year except adequately treated basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic therapy

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Concurrent corticosteroids for brain metastases allowed

Radiotherapy

• See Disease Characteristics
• Prior radiotherapy to any symptomatic site allowed provided the target site(s) was not previously irradiated
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Contacts and Locations

Locations

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United States, Wisconsin
Gundersen Lutheran Center for Cancer and Blood
La Crosse, Wisconsin, United States, 54601

Sponsors and Collaborators

Gundersen Lutheran Health System

Investigators

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Study Chair:	Ronald S. Go, MD	Gundersen Lutheran Center for Cancer and Blood

More Information

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Responsible Party:	Ronald Go, Hematologist, Gundersen Lutheran Health System
ClinicalTrials.gov Identifier:	NCT00083161 History of Changes
Other Study ID Numbers:	CDR0000363799; GLO-03-06-06
First Posted:	May 17, 2004
Last Update Posted:	September 5, 2012
Last Verified:	September 2012

Keywords provided by Ronald Go, Gundersen Lutheran Health System:

extensive stage small cell lung cancer; recurrent small cell lung cancer

Additional relevant MeSH terms:

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Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Cisplatin; Cyclophosphamide; Etoposide; Etoposide phosphate	Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors