Small Cell Lung Cancer
Conditions
Keywords
Small Cell Lung Cancer, Extensive Stage, irinotecan, carboplatin, sunitinib
Brief summary
This proposed Phase II trial will investigate the combination of irinotecan and carboplatin followed by sunitinib in the first-line treatment of patients with extensive-stage SCLC.
Detailed description
Irinotecan/platinum regimens are emerging as standard treatments for patients with extensive-stage disease. The irinotecan/carboplatin doses that will be used in this study have been used in two previous Phase II SCLC trials, and were found to be extremely well tolerated (Thompson et al. 2005; Spigel et al. 2007). Adding a novel, minimally toxic agent to this regimen may further enhance efficacy in this patient population without contributing to toxicity. This trial will evaluate the use of sunitinib following 6 cycles of treatment with chemotherapy in the treatment of SCLC. The trial will be performed under the leadership of SCRI, a community-based, multi-center, clinical trial organization.
Interventions
DRUGirinotecan
irinotecan 60 mg/m2 intravenously (IV) on Days 1, 8, and 15
DRUGCarboplatin
carboplatin AUC=4 on Day 1
DRUGsunitinib
sunitinib 25 mg orally (PO) daily after initial chemotherapy
Sponsors
Pfizer
SCRI Development Innovations, LLC
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
1. Cytologically and/or histologically confirmed small-cell lung cancer with extensive-stage disease. 2. Measurable or evaluable disease. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 4. Adequate bone marrow function, as defined by: absolute neutrophil count (ANC) \>1,500/µL; platelets \>100,000/µL; hemoglobin \>=9.0 g/dL. 5. Normal organ function, defined as follows: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=2.5 × the upper limit of normal (ULN), or AST and ALT \<=5 × the ULN if liver function abnormalities are due to underlying malignancy; total serum bilirubin \<=1.5 × the ULN; serum creatinine \<=1.5 × the ULN. 6. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade \<=1. 7. Women of childbearing potential and men with partners of childbearing potential must agree to use a form of birth control that is acceptable to their physician to prevent pregnancy during treatment. 8. Patients must be informed of the investigational nature of this study and sign an informed consent form. 9. Patients who have treated brain metastases \>=4 weeks out (with surgery and/or radiation therapy) and who have no evidence of central nervous system (CNS) progression. Steroid use should be discontinued before study treatment begins.
Exclusion criteria
1. Patients who are pregnant or breastfeeding. 2. Patients may not have received other agents (either investigational or marketed) which act by anti-angiogenic mechanisms. Angiogenesis inhibitors include (but are not limited to): thalidomide, sorafenib, bevacizumab. 3. Patients who have had previous chemotherapy or radiation therapy for extensive-stage disease will be excluded. Palliative radiation (e.g., for bone disease) or radiation for cranial metastasis is acceptable if the patient has recovered from any adverse effects. 4. Previous treatment with sunitinib. 5. Myocardial infarction, severe or unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (CHF), cerebrovascular accident (including transient ischemic attack), or pulmonary embolism within 6 months prior to study initiation. 6. Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade \>=2, atrial fibrillation of any grade, or prolongation of the QTc interval to \>450 msec (for males) or \>470 msec (for females). 7. Uncontrolled hypertension (i.e., blood pressure \>150 mm Hg that cannot be controlled with standard anti-hypertensive agents). 8. Active brain metastasis. (Patients who had brain metastases treated with radiation or surgery and have no evidence of progressive brain metastases at least 4 weeks later are eligible). 9. Patients who have had major surgical procedure, open biopsy, or significant traumatic injury with 28 days (4 weeks) of study initiation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment | 18 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 18 months | Objective benefit is defined as substantial (30% or greater) shrinkage in tumor volume per RECIST 1.0. |
| Time to Progression | 18 months | Time To Progression (TTP) was defined as the interval between the start date of treatment and the date of occurrence of progressive disease |
| Median Overall Survival | 18 months | Overall survival was defined as the interval between the date of study entry until the date of death. |
| Number of Participants Experiencing Treatment Related Toxicity | 18 months | The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Irinotecan, Carboplatin, Sunitinib Patients receive irinotecan 60mg/m2 IV on days 1, 8, and 15 and carboplatin AUC=4 on day 1 of each 28-day cycle. After completion of 6 cycles, patients receive only sunitinib 25 mg daily by mouth. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Irinotecan, Carboplatin, Sunitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 19 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 37 |
| serious Total, serious adverse events | 18 / 37 |
Outcome results
Primary
One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment
Time frame: 18 months
Population: The original study design administered sunitinib concurrently with irinotecan/carboplatin. After the first three patients enrolled experienced severe myelosuppression, the treatment plan was modified to delay sunitinib until after completion of combination therapy. Only patients treated under the revised plan are included in the results analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irinotecan, Carboplatin, Sunitinib | One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment | 54 percentage of participants |
Secondary
Median Overall Survival
Overall survival was defined as the interval between the date of study entry until the date of death.
Time frame: 18 months
Population: The original study design administered sunitinib concurrently with irinotecan/carboplatin. After the first three patients enrolled experienced severe myelosuppression, the treatment plan was modified to delay sunitinib until after completion of combination therapy. Only patients treated under the revised plan are included in the results analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan, Carboplatin, Sunitinib | Median Overall Survival | NA months |
Secondary
Number of Participants Experiencing Treatment Related Toxicity
The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here.
Time frame: 18 months
Population: Toxicity was evaluated in all patients who received at least 1 dose of therapy. The original study design administered sunitinib concurrently with irinotecan/carboplatin. After the first three patients enrolled experienced severe myelosuppression, the treatment plan was modified to delay sunitinib until after completion of combination therapy. Only patients treated under the revised plan are included in the results analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Irinotecan, Carboplatin, Sunitinib | Number of Participants Experiencing Treatment Related Toxicity | 32 Participants |
Secondary
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Objective benefit is defined as substantial (30% or greater) shrinkage in tumor volume per RECIST 1.0.
Time frame: 18 months
Population: The original study design administered sunitinib concurrently with irinotecan/carboplatin. After the first three patients enrolled experienced severe myelosuppression, the treatment plan was modified to delay sunitinib until after completion of combination therapy. Only patients treated under the revised plan are included in the results analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irinotecan, Carboplatin, Sunitinib | Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 59 percentage of participants |
Secondary
Time to Progression
Time To Progression (TTP) was defined as the interval between the start date of treatment and the date of occurrence of progressive disease
Time frame: 18 months
Population: The original study design administered sunitinib concurrently with irinotecan/carboplatin. After the first three patients enrolled experienced severe myelosuppression, the treatment plan was modified to delay sunitinib until after completion of combination therapy. Only patients treated under the revised plan are included in the results analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Irinotecan, Carboplatin, Sunitinib | Time to Progression | 7.6 months |