Irinotecan, Carboplatin, and Sunitinib in First Line Extensive-Stage Small Cell Lung Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Intervention 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
irinotecan 60 mg/m2 intravenously (IV) on Days 1, 8, and 15
Other Names:
Drug: Carboplatin
carboplatin AUC=4 on Day 1
Other Names:
Drug: sunitinib
sunitinib 25 mg orally (PO) daily after initial chemotherapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment [18 months]
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Florida Cancer Specialists | Fort Myers | Florida | United States | 33901 |
2 | Florida Hospital Cancer Insitute | Orlando | Florida | United States | 32804 |
3 | Northeast Georgia Medical Center | Gainesville | Georgia | United States | 30501 |
4 | Baton Rouge General Medical Center | Baton Rouge | Louisiana | United States | 70806 |
5 | Center for Cancer and Blood Disorders | Bethesda | Maryland | United States | 20817 |
6 | St. Louis Cancer Care | Chesterfield | Missouri | United States | 63017 |
7 | Oncology Hematology Care | Cincinnati | Ohio | United States | 45242 |
8 | Spartanburg Regional Medical Center | Spartanburg | South Carolina | United States | 29303 |
9 | Chattanooga Oncology Hematology Associates | Chattanooga | Tennessee | United States | 37404 |
10 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- SCRI Development Innovations, LLC
- Pfizer
Investigators
- Study Chair: David R Spigel, M.D., SCRI Development Innovations, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SCRI LUN 156
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Period Title: Overall Study | |
STARTED | 37 |
COMPLETED | 37 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Overall Participants | 37 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
18
48.6%
|
>=65 years |
19
51.4%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
64
(9.9)
|
Sex: Female, Male (Count of Participants) | |
Female |
16
43.2%
|
Male |
21
56.8%
|
Region of Enrollment (participants) [Number] | |
United States |
37
100%
|
Outcome Measures
Title | One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment |
---|---|
Description | |
Time Frame | 18 months |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Measure Participants | 34 |
Number [percentage of participants] |
54
145.9%
|
Title | Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment |
---|---|
Description | Objective benefit is defined as substantial (30% or greater) shrinkage in tumor volume per RECIST 1.0. |
Time Frame | 18 months |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Measure Participants | 34 |
Number (95% Confidence Interval) [percentage of participants] |
59
159.5%
|
Title | Time to Progression |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Measure Participants | 34 |
Median (95% Confidence Interval) [months] |
7.6
|
Title | Median Overall Survival |
---|---|
Description | Overall survival was defined as the interval between the date of study entry until the date of death. |
Time Frame | 18 months |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Measure Participants | 34 |
Median (95% Confidence Interval) [months] |
NA
|
Title | Number of Participants Experiencing Treatment Related Toxicity |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Irinotecan, Carboplatin, Sunitinib |
---|---|
Arm/Group Description | 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. |
Measure Participants | 34 |
Count of Participants [Participants] |
32
86.5%
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Intervention | |
Arm/Group Description | 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. | |
All Cause Mortality |
||
Intervention | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Intervention | ||
Affected / at Risk (%) | # Events | |
Total | 18/37 (48.6%) | |
Blood and lymphatic system disorders | ||
Pancytopenia | 1/37 (2.7%) | 1 |
Platelets | 1/37 (2.7%) | 1 |
Cardiac disorders | ||
Pain - Chest | 1/37 (2.7%) | 1 |
Gastrointestinal disorders | ||
Diverticulitis | 1/37 (2.7%) | 1 |
Dysphagia | 1/37 (2.7%) | 1 |
Vomiting | 1/37 (2.7%) | 2 |
Diarrhea | 1/37 (2.7%) | 1 |
General disorders | ||
Death | 1/37 (2.7%) | 1 |
Intractable Pain | 1/37 (2.7%) | 1 |
Infections and infestations | ||
Infection - Sepsis | 2/37 (5.4%) | 2 |
Infection - Pneumonia | 1/37 (2.7%) | 1 |
Metabolism and nutrition disorders | ||
Dehydration | 2/37 (5.4%) | 2 |
Hypokalemia | 1/37 (2.7%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Disease Progression | 4/37 (10.8%) | 4 |
Nervous system disorders | ||
Dizziness | 1/37 (2.7%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnea | 2/37 (5.4%) | 2 |
ARDS | 2/37 (5.4%) | 2 |
Other (Not Including Serious) Adverse Events |
||
Intervention | ||
Affected / at Risk (%) | # Events | |
Total | 34/37 (91.9%) | |
Blood and lymphatic system disorders | ||
Edema: Limb | 7/37 (18.9%) | 20 |
Hemoglobin | 34/37 (91.9%) | 117 |
Hemorrhage - Nose | 2/37 (5.4%) | 2 |
Hemorrhage, Pulmonary/Upper Respiratory | 2/37 (5.4%) | 2 |
Leukocytes | 31/37 (83.8%) | 93 |
Neutrophils | 28/37 (75.7%) | 64 |
Platelets | 23/37 (62.2%) | 53 |
Cardiac disorders | ||
Hypertension | 2/37 (5.4%) | 3 |
Hypotension | 6/37 (16.2%) | 15 |
Superventricular Arrhythmia (Atrial Fibrillation) | 2/37 (5.4%) | 2 |
Supraventricular Arrhythmia (Tachycardia) | 3/37 (8.1%) | 4 |
Gastrointestinal disorders | ||
Anorexia | 11/37 (29.7%) | 21 |
Constipation | 13/37 (35.1%) | 40 |
Dehydration | 11/37 (29.7%) | 11 |
Diarrhea | 20/37 (54.1%) | 64 |
Esophagitis | 4/37 (10.8%) | 4 |
Heartburn | 8/37 (21.6%) | 22 |
Mucositis/Stomatitis | 8/37 (21.6%) | 10 |
Nausea | 27/37 (73%) | 72 |
Taste Alteration | 5/37 (13.5%) | 9 |
Vomiting | 14/37 (37.8%) | 40 |
General disorders | ||
Fatigue | 30/37 (81.1%) | 117 |
Fever | 6/37 (16.2%) | 7 |
Insomnia | 8/37 (21.6%) | 12 |
Pain - Muscle | 4/37 (10.8%) | 5 |
Pain - Other | 4/37 (10.8%) | 10 |
Pain - Abdomen | 8/37 (21.6%) | 19 |
Pain - Back | 7/37 (18.9%) | 17 |
Pain - Bone | 4/37 (10.8%) | 7 |
Pain - Chest | 8/37 (21.6%) | 12 |
Pain - Dental/Teeth/Periodontal | 2/37 (5.4%) | 3 |
Pain - Head | 7/37 (18.9%) | 12 |
Pain - Joint | 11/37 (29.7%) | 28 |
Pain - Limb | 6/37 (16.2%) | 12 |
Rigors/Chills | 2/37 (5.4%) | 2 |
Sweating | 4/37 (10.8%) | 5 |
Infections and infestations | ||
Febrile Neutropenia | 2/37 (5.4%) | 2 |
Infection - Other | 2/37 (5.4%) | 2 |
Infection - Pneumonia | 5/37 (13.5%) | 6 |
Metabolism and nutrition disorders | ||
AST | 2/37 (5.4%) | 3 |
Creatinine | 2/37 (5.4%) | 2 |
Hyperglycemia | 4/37 (10.8%) | 12 |
Hyperkalemia | 2/37 (5.4%) | 2 |
Hypocalcemia | 5/37 (13.5%) | 9 |
Hypokalemia | 8/37 (21.6%) | 12 |
Hypomagnesemia | 2/37 (5.4%) | 10 |
Hyponatremia | 9/37 (24.3%) | 10 |
Weight Gain | 2/37 (5.4%) | 3 |
Weight Loss | 5/37 (13.5%) | 6 |
Musculoskeletal and connective tissue disorders | ||
Gait/Walking | 2/37 (5.4%) | 2 |
Muscle Weakness (Extremity-Lower) | 3/37 (8.1%) | 4 |
Muscle Weakness (NOS) | 2/37 (5.4%) | 3 |
Nervous system disorders | ||
Ataxia | 2/37 (5.4%) | 2 |
Dizziness | 7/37 (18.9%) | 16 |
Neuropathy: Motor | 2/37 (5.4%) | 3 |
Neuropathy: Sensory | 4/37 (10.8%) | 9 |
Tremor | 2/37 (5.4%) | 2 |
Psychiatric disorders | ||
Mood Alteration - Anxiety | 5/37 (13.5%) | 16 |
Renal and urinary disorders | ||
Renal Failure | 2/37 (5.4%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 7/37 (18.9%) | 12 |
Dyspnea | 14/37 (37.8%) | 58 |
Pneumonitis | 3/37 (8.1%) | 3 |
Pulmonary, Other (COPD) | 3/37 (8.1%) | 3 |
Rhinitis | 5/37 (13.5%) | 5 |
Skin and subcutaneous tissue disorders | ||
Alopecia | 4/37 (10.8%) | 15 |
Rash/Desquamation | 3/37 (8.1%) | 8 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Results Point of Contact
Name/Title | Dr. David Spigel |
---|---|
Organization | Sarah Cannon Research Institute |
Phone | 615-329-7274 |
askSARAH@scresearch.net |
- SCRI LUN 156