Carboplatin and Etoposide With or Without Thalidomide in Treating Patients With Limited-Stage or Extensive-Stage Small Cell Lung Cancer

A Phase III Randomized, Double Blind, Placebo Controlled Trial Of Carboplatin/Etoposide With Or Without Thalidomide In Small Cell Lung Cancer (Study 12)

RATIONALE: Drugs used in chemotherapy such as carboplatin and etoposide use different ways to stop tumor cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. It is not yet known if combination chemotherapy is more effective with or without thalidomide in treating small cell lung cancer.

PURPOSE: This randomized phase III trial is studying carboplatin, etoposide, and thalidomide to see how well they work compared to carboplatin and etoposide in treating patients with limited- or extensive-stage small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Carboplatin, etoposide & thalidomide; Drug: Carboplatin, etoposide & placebo

Detailed Description

OBJECTIVES:

• Compare the survival of patients with limited or extensive stage small cell lung cancer treated with carboplatin and etoposide with vs without thalidomide.
• Compare the time to disease progression in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the response rates of patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (limited vs extensive), ECOG performance status (0 and 1 vs 2), and alkaline phosphatase (no greater than 1.5 times upper limit of normal [ULN] vs greater than 1.5 times ULN). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive carboplatin IV over 30 minutes on day 1 and etoposide* IV over 1-2 hours on days 1 and 2 and orally on day 3. Patients also receive oral thalidomide daily beginning on day 1.
• Arm II: Patients receive carboplatin and etoposide as in arm I and oral placebo daily beginning on day 1.

NOTE: *Patients who are unable to receive etoposide IV on day 2 may receive oral etoposide on days 2 and 3.

In both arms, chemotherapy (carboplatin and etoposide) repeats every 3 weeks for up to 6 courses. Patients receive thalidomide or placebo continuously for up to 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may continue to receive thalidomide or placebo provided the patient is clinically and symptomatically stable.

Quality of life is assessed at baseline, during each course of chemotherapy, at 3-4 weeks after completion of chemotherapy, and at 6, 12, 18, and 24 months.

Patients are followed every 2 months for 2 years after the completion of chemotherapy and then every 3 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 372 patients (186 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 724
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, WIT 3AA
      • University College of London Hospitals

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

  • Limited or extensive stage disease
• No symptomatic brain metastases requiring immediate radiotherapy

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-3

Life expectancy

• At least 8 weeks

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Ethylenediamine tetraacetic acid (EDTA) clearance greater than 60 mL/min OR
• Creatinine clearance greater than 50 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective methods of contraception (including 1 highly effective method and 1 barrier method) during and for 4 weeks after study completion
• No other prior malignancy within the past 3 years except nonmelanoma skin cancer or early cervical cancer
• No significant medical condition or laboratory finding that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm (thalidomide); Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral thalidomide daily beginning on day 1 for up to 24 months.	Drug: Carboplatin, etoposide & thalidomide; Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral thalidomide daily beginning on day 1 for up to 24 months.
Placebo Comparator: Placebo arm; Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral placebo daily beginning on day 1 for up to 24 months.	Drug: Carboplatin, etoposide & placebo; Carboplatin IV on day 1 and etoposide IV on day 1 and 2 and, orally Day 3. Oral placebo daily beginning on day 1 for up to 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Survival at 2 years after study randomization	0-2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to disease progression 2 years after study randomization	0-2 years
Toxicity as measured by NCIC CTC 3 times weekly while undergoing chemotherapy, then monthly thereafter	Till end of treatment
Response rates as measured by RECIST during each visit while undergoing chemotherapy and after completion of study treatment	Till progression
Quality of life as measured by EORTC QLQ-30 and lung-specific questionnaire(LC14) at baseline, after each course, and after completion of study treatment, and at 6, 12, 18, and 24 months after day 1 of course 1	0-24 months
Biological markers (measurement of VEGF, bFGF, TNF alpha, and IL-6)	Before treatment courses 1 and 4, and then at 9 and 18 months

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Study Chair: Siow M. Lee, MD, PhD, FRCP, University College London Hospitals

Publications and helpful links

General Publications

• Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. doi: 10.1093/jnci/djp200. Epub 2009 Jul 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: June 5, 2003
• First Submitted That Met QC Criteria: June 5, 2003
• First Posted (Estimate): June 6, 2003

Study Record Updates

• Last Update Posted (Estimate): March 16, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: extensive stage small cell lung cancer; limited stage small cell lung cancer
• 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; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Carboplatin; Etoposide; Etoposide phosphate; Thalidomide
• Other Study ID Numbers: CDR0000302440; LLCG-STUDY-12 (Other Identifier: UCL CTC); EU-20207 (Other Identifier: UCL CTC); ISRCTN16174527 (Registry Identifier: ISRCTN)