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

Phase 2

Completed

Brief Summary: 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.

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.

Recruitment & Eligibility

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:

Arm && Interventions

Group	Intervention	Description
Therapeutic Intervention	Carboplatin	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.
Therapeutic Intervention	irinotecan hydrochloride	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.

Primary Outcome Measures

Name	Time	Method
Patient Response	1.66 months (average duration, on treatment date to best response date)	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

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Adverse Events	date off treatment or progression of disease, up to 18 weeks	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
Time to Progression	9.9 months (on study date to progression)	Time to progression in months
Overall Survival	On study date to death

Locations (8): Tennessee Cancer Specialists
🇺🇸
Knoxville, Tennessee, United States
Owensboro Medical Health System
🇺🇸
Owensboro, Kentucky, United States
British Columbia Cancer Agency - Vancouver Cancer Centre
🇨🇦
Vancouver, Canada
St. Thomas Health Services
🇺🇸
Nashville, Tennessee, United States
MBCCOP - Meharry Medical College - Nashville
🇺🇸
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
West Tennessee Cancer Center at Jackson-Madison County General Hospital
🇺🇸
Jackson, Tennessee, United States
Memorial Health Care System
🇺🇸
Chattanooga, Tennessee, United States