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

Phase 2

Completed

• Conditions: Small Cell Lung Cancer
• Interventions: Drug: irinotecan; Drug: Carboplatin; Drug: sunitinib

• Registration Number: NCT00695292
• Lead Sponsor: SCRI Development Innovations, LLC

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.

Study Timeline

• Study Start: 2008-06
• Study First Submitted: 2008-06-09
• Study First Submitted QC: 2008-06-09
• Study First Posted: 2008-06-11
• Primary Completion: 2011-06
• Study Completion: 2012-09
• Results First Submitted: 2013-01-14
• Results First Submitted QC: 2013-01-14
• Results First Posted: 2013-02-15
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-19
• Last Update Posted: 2021-11-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	irinotecan	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.
Intervention	Carboplatin	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.
Intervention	sunitinib	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.

Primary Outcome Measures

Name	Time	Method
One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment	18 months

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (10)

Oncology Hematology Care; 🇺🇸 Cincinnati, Ohio, United States

Florida Hospital Cancer Insitute; 🇺🇸 Orlando, Florida, United States

Northeast Georgia Medical Center; 🇺🇸 Gainesville, Georgia, United States

Florida Cancer Specialists; 🇺🇸 Fort Myers, Florida, United States

Baton Rouge General Medical Center; 🇺🇸 Baton Rouge, Louisiana, United States

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

St. Louis Cancer Care; 🇺🇸 Chesterfield, Missouri, United States

Spartanburg Regional Medical Center; 🇺🇸 Spartanburg, South Carolina, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Chattanooga Oncology Hematology Associates; 🇺🇸 Chattanooga, Tennessee, United States