Lung Cancer
Conditions
Keywords
extensive stage small cell lung cancer
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.
Interventions
DRUGCarboplatin
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
DRUGirinotecan hydrochloride
50 mg/m2 IV on days 1 and 8 every 21 days Should be infused IV over 30- 90 minutes.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Canada, United States
Participant flow
Recruitment details
Recruitment Period = 2/18/2004 through 1/23/2007
Pre-assignment details
A total of 54 people signed consent to take part in the study. Of those, 3 were found to be ineligible and 1 withdrew before beginning the study.
Participants by arm
| Arm | Count |
|---|---|
| Therapeutic Intervention | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 4 |
| Overall Study | Decreased performance status | 1 |
| Overall Study | Disease progression | 9 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Therapeutic Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants |
| Age Continuous | 59.5 years STANDARD_DEVIATION 1 |
| Region of Enrollment Canada | 5 participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 50 |
| serious Total, serious adverse events | 26 / 50 |
Outcome results
Primary
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
Time frame: 1.66 months (average duration, on treatment date to best response date)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic Intervention | Patient Response | Partial Response | 27 participants |
| Therapeutic Intervention | Patient Response | Progressive Disease | 12 participants |
| Therapeutic Intervention | Patient Response | Stable Disease | 1 participants |
| Therapeutic Intervention | Patient Response | Unknown | 5 participants |
| Therapeutic Intervention | Patient Response | Complete Response | 2 participants |
| Therapeutic Intervention | Patient Response | Not Assessed | 1 participants |
| Therapeutic Intervention | Patient Response | Not Evaluable | 2 participants |
Secondary
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
Time frame: date off treatment or progression of disease, up to 18 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic Intervention | Number of Patients With Adverse Events | Grade 2 | 26 participants |
| Therapeutic Intervention | Number of Patients With Adverse Events | Grade 1 | 13 participants |
| Therapeutic Intervention | Number of Patients With Adverse Events | Grade 3 | 29 participants |
| Therapeutic Intervention | Number of Patients With Adverse Events | Grade 4 | 10 participants |
| Therapeutic Intervention | Number of Patients With Adverse Events | Grade 5 | 4 participants |
Secondary
Overall Survival
Time frame: On study date to death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Therapeutic Intervention | Overall Survival | 9 Months |
Secondary
Time to Progression
Time to progression in months
Time frame: 9.9 months (on study date to progression)
Population: Patients who has progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Therapeutic Intervention | Time to Progression | 5 Months |