Irinotecan and Carboplatin as First-Line Therapy in Treating Patients With Extensive-Stage Small Cell Lung Cancer

A Phase II Trial of Carboplatin and Irinotecan (CPT-11) as First-Line Therapy for Patients With Extensive Stage Small Cell Lung Cancer

RATIONALE: The general results of combining irinotecan and platin-based chemotherapies have been very encouraging. As the toxicity profile associated with carboplatin is preferable over cisplatin it is our expectation that patients and physicians would prefer to use this combination if it is equally or more efficacious. To date there has been no agreement regarding the optimal combination of these agents. Based on the trials described in the protocol and our experience with carboplatin/irinotecan in the treatment of non-small cell lung cancer the present trial will utilize a 21-day cycle of irinotecan 50 mg/m2 given on days 1 and 8 and carboplatin AUC 5 (based on the Calvert formula) on day 1.

PURPOSE: This phase II trial is studying how well giving irinotecan together with carboplatin works as first-line therapy in treating patients with extensive-stage small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: irinotecan hydrochloride

Detailed Description

OBJECTIVES:

Primary

• To examine the anti-tumor efficacy of the combination of Irinotecan (CPT-11) and Carboplatin as first-line therapy as assessed by response rate in patients with chemo-naïve extensive stage small cell lung cancer.

Secondary

• Determine the safety, tolerability, and feasibility of this regimen in these patients.
• Determine the time to progression in patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, open-label study.

Patients receive irinotecan IV over 30-90 minutes on days 1 and 8 and carboplatin IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Vancouver, Canada, V52 4
    • British Columbia Cancer Agency - Vancouver Cancer Centre
• United States
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Owensboro Medical Health System
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Health Care System
    • Jackson, Tennessee, United States, 38301
      • West Tennessee Cancer Center at Jackson-Madison County General Hospital
    • Knoxville, Tennessee, United States, 37901
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37208
      • MBCCOP - Meharry Medical College - Nashville
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Health Services

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

Inclusion Criteria:

• Histologically or cytologically confirmed small cell lung cancer (SCLC)

  • Extensive stage small cell lung cancer

• Must have ≥ 1 unidimensionally measurable lesion (longest diameter to be recorded) ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

  • Lesion cannot be from a previously irradiated area

  • Lesions that are considered nonmeasurable include the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
    • Tumor lesions in a previously irradiated area
• No brain metastasis or carcinomatous meningitis unless stable and asymptomatic

PATIENT CHARACTERISTICS

• ECOG performance status 0-2
• Life expectancy ≥ 3 months
• ANC ≥ 1,500/mm³
• Platelet count > 100,000/mm³
• Serum bilirubin ≤ 1.5 mg/dL
• AST/SGOT ≤ 2.5 times upper limit of normal (ULN) (or ≤ 5 times ULN if liver metastases present)
• Serum creatinine ≤ 2.0 mg/dl
• Hemoglobin ≥ 9.0 g/dl

Exclusion Criteria:

• CNS metastasis excluded unless: stable and asymptomatic
• Coexisting medical condition that would preclude study compliance
• Patients with Gilbert's disease
• Uncontrolled diabetes mellitus, defined as random blood sugar ≥ 300 mg/dl or > 16.6 mmol/L
• Patients who do not discontinue phenytoin, phenobarbitol, carbamazipine, or other enzyme-inducing anticonvulsant drugs at least 7 days prior to first treatment dose on study. Gabapentin is permitted
• Patients who do not discontinue St. John's Wort prior to first treatment dose on study.
• Patients who are pregnant or breast feeding
• Concomitant second active malignancy except for any in situ cancer or adequately treated basal cell or squamous cell skin cancer or any cancer from which the patients has been disease-free for at least 2 years
• No administration of any prior systemic anticancer therapy for extensive stage SCLC such as: chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, or other experimental agents. Concurrent use of other anticancer therapy including inhibitors of vascular endothelial or epidermal growth factor pathways is prohibited. Prior radiation is allowed
• Symptomatic brain metastasis or carcinomatous meningitis

PRIOR CONCURRENT THERAPY:

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Therapeutic Intervention; Lung cancer patients will be treated for four 3-week cycles (12 weeks) in the absence of progressive disease, unacceptable toxicity, or withdrawal of patient consent. Up to two additional cycles may be administered at the discretion of the treating physician. If at treatment withdrawal the disease has responded or is stable, the patient will continue to be followed for efficacy (i.e. until progressive disease)at 8 week intervals. Following the diagnosis of progressive disease, patients will be followed every two months for survival.

Drug: Carboplatin; Carboplatin dosage calculation to be given on day 1, every 21 days: Carboplatin (mg) = (AUC of 5) x (GFR + 25) *up to 6 cycles at physician's discretion; Other Names: Paraplatin; Drug: irinotecan hydrochloride; 50 mg/m2 IV on days 1 and 8 every 21 days Should be infused IV over 30- 90 minutes.; Other Names: Irinotecan; Camptosar; CPT-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Response	Patient response to treatment: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started Complete response (CR): disappearance of all target lesions Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD	1.66 months (average duration, on treatment date to best response date)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events	Number of participants with adverse events, according to grade of event, using the NCI Common Toxicity Criteria (version 2.0) grading system to assign a grade to each event	date off treatment or progression of disease, up to 18 weeks
Time to Progression	Time to progression in months	9.9 months (on study date to progression)
Overall Survival		On study date to death

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Leora Horn, MD, Vanderbilt-Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimate): May 7, 2007

Study Record Updates

• Last Update Posted (Estimate): July 27, 2012
• Last Update Submitted That Met QC Criteria: July 20, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: extensive 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Irinotecan
• Other Study ID Numbers: VICC THO 0321; VU-VICC-THO-0321