Irinotecan, Carboplatin, and Sunitinib in First Line Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study of Irinotecan, Carboplatin, and Sunitinib in the First Line Treatment of Extensive-Stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: irinotecan
* Drug: Carboplatin
* Drug: sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically and/or histologically confirmed small-cell lung cancer with extensive-stage disease. Measurable or evaluable disease. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. Adequate bone marrow function, as defined by: absolute neutrophil count (ANC) >1,500/µL; platelets >100,000/µL; hemoglobin >=9.0 g/dL. 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. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade <=1. 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. Patients must be informed of the investigational nature of this study and sign an informed consent form. 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: Patients who are pregnant or breastfeeding. 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. 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. Previous treatment with sunitinib. 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. 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). Uncontrolled hypertension (i.e., blood pressure >150 mm Hg that cannot be controlled with standard anti-hypertensive agents). 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). Patients who have had major surgical procedure, open biopsy, or significant traumatic injury with 28 days (4 weeks) of study initiation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Patients in the study will receive the following for the duration of the study: irinotecan 60 mg/m2 intravenously on Days 1, 8, and 15 and carboplatin AUC=4 on Day 1. The study will consist of 28-day cycles, to a maximum of 6 cycles of therapy with irinotecan and carboplatin. After treatment with irinotecan and carboplatin, sunitinib will be given alone as maintenance therapy in all patients who have achieved study entry hematologic criteria and who do not have progressive disease or severe toxicity. During sunitinib maintenance therapy, patients will receive sunitinib at 25 mg orally daily. Sunitinib maintenance therapy will continue until progressive disease or irreversible toxicity occurs. Re-staging will be performed every 2 cycles (every 8 weeks) during the study. | Drug: irinotecan<br>* irinotecan 60 mg/m2 intravenously (IV) on Days 1, 8, and 15<br>* Other names: Camptosar;Drug: Carboplatin<br>* carboplatin AUC=4 on Day 1<br>* Other names: Paraplatin;Drug: sunitinib<br>* sunitinib 25 mg orally (PO) daily after initial chemotherapy<br>* Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 18 months | 
| 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 | 18 months | 
| Median Overall Survival | Overall survival was defined as the interval between the date of study entry until the date of death. | 18 months | 
| 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. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small Cell Lung Cancer, Extensive Stage, irinotecan, carboplatin, sunitinib