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

Sponsor
SCRI Development Innovations, LLC (Other)
Overall Status
Completed
CT.gov ID
NCT00695292
Collaborator
Pfizer (Industry)
37
10
1
51
3.7
0.1

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

Study Type:
Interventional
Actual Enrollment :
37 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Irinotecan, Carboplatin, and Sunitinib in the First Line Treatment of Extensive-Stage Small Cell Lung Cancer
Study Start Date :
Jun 1, 2008
Actual Primary Completion Date :
Jun 1, 2011
Actual Study Completion Date :
Sep 1, 2012

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:
  • Camptosar
  • Drug: Carboplatin
    carboplatin AUC=4 on Day 1
    Other Names:
  • Paraplatin
  • Drug: sunitinib
    sunitinib 25 mg orally (PO) daily after initial chemotherapy
    Other Names:
  • Sutent
  • Outcome Measures

    Primary Outcome Measures

    1. One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment [18 months]

    Secondary Outcome Measures

    1. 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.

    2. 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

    3. Median Overall Survival [18 months]

      Overall survival was defined as the interval between the date of study entry until the date of death.

    4. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    1. 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.

    2. Resolution of all acute toxic effects of prior therapy or surgical procedures to grade <=1.

    3. 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.

    4. Patients must be informed of the investigational nature of this study and sign an informed consent form.

    5. 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.

    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.
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT00695292
    Other Study ID Numbers:
    • SCRI LUN 156
    First Posted:
    Jun 11, 2008
    Last Update Posted:
    Nov 22, 2021
    Last Verified:
    Nov 1, 2021
    Keywords provided by SCRI Development Innovations, LLC
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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%
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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

    [Not Specified]

    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
    Email askSARAH@scresearch.net
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT00695292
    Other Study ID Numbers:
    • SCRI LUN 156
    First Posted:
    Jun 11, 2008
    Last Update Posted:
    Nov 22, 2021
    Last Verified:
    Nov 1, 2021