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| ID | Type | Description | Link |
|---|---|---|---|
| HUM12046 | Other Identifier | IRBMED (University of Michigan Medical School IRB) |
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The goal of this study is to determine the progression-free survival rate in patients with extensive-stage small cell lung cancer who had achieved complete response, partial response, or stable disease with their previous platinum chemotherapy regimen, such as cisplatin or carboplatin in combination with etoposide or irinotecan. In addition, the safety and effectiveness of sunitinib will also be evaluated.
Despite a high initial response rate, all patients with extensive-stage small cell lung cancer treated with standard chemotherapy will develop disease progression, usually within one year of initial treatment. Therefore, prolonging progression-free survival in this disease is meaningful for clinical trials exploring agents such as sunitinib. Sunitinib is a drug that inhibits the biological pathway responsible for the growth and spread of cancer cells. For this reason, we believe that sunitinib maintenance therapy will delay or prevent recurrence and prolong survival.
The goal of this study is to determine the progression-free survival rate in patients with extensive-stage small cell lung cancer who had achieved complete response, partial response, or stable disease with their previous platinum chemotherapy regimen, such as cisplatin or carboplatin in combination with etoposide or irinotecan. In addition, the safety and effectiveness of sunitinib will also be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Maintenance Sunitinib | Experimental | Main interventional arm of study. Subjects who received maintenance sunitinib experimentally on this study were from a population of (consenting) patients with histologically or cytologically documented Extensive-State Small Cell Lung Cancer (ES-SCLC) who did not progress (were classified as Complete Response or "CR", Partial Response or "PR", or Stable Disease or "SD") after an induction chemotherapy (Cisplatin and etoposide) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sunitinib | Drug | Sunitinib will be given at 50 mg/day as a single agent for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival Rate | The proportion of patients who are progression-free at 4 months after starting sunitinib. | 4 Months Post Treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Median Overall Survival | Survival will be defined as the time from the first day of therapy to the date of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. Survival for induction therapy will be calculated from day 1 of first cycle of chemotherapy. Survival for post-induction therapy will be calculated from the date the patient starts sunitinib. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gregory Kalemkerian, MD | University of Michigan Rogel Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | 48109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21512407 | Result | Schneider BJ, Gadgeel SM, Ramnath N, Wozniak AJ, Dy GK, Daignault S, Kalemkerian GP. Phase II trial of sunitinib maintenance therapy after platinum-based chemotherapy in patients with extensive-stage small cell lung cancer. J Thorac Oncol. 2011 Jun;6(6):1117-20. doi: 10.1097/JTO.0b013e31821529c3. |
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Patients with histologically or cytologically documented Extensive-Stage Small Cell Lung Cancer (ES-SCLC) who had received no more than 4 cycles of frontline platinum plus etoposide chemotherapy and who demonstrated a response or stable disease were eligible. ES-SCLC was defined as disease extending beyond 1 hemothorax and regional lymph nodes.
16 subjects recruited from 7/19/2007 to 2/1/2010 at University of Michigan, Ann Arbor(lead site), and sub-sites: The University of Detroit's Karmanos Cancer Institute, WSU, Detroit; Weill Cornell Medical College, NY; and Roswell Park Cancer Institute, NJ
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| ID | Title | Description |
|---|---|---|
| FG000 | Sunitinib Maintenance Therapy | Sunitinib 50 mg po QD × 28 days followed by a 14 day break every 42 days until disease progression or unacceptable toxicity. Treatment to begin 28-42 days after day 1 of the last cycle of induction chemotherapy to allow confirmation of response or disease stability with chemotherapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Lung cancer patients who are greater than or equal to 18 years old, who have had a response or maintained stable disease after undergoing no more that 4 cycles with platinum with etoposide chemotherapy
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| ID | Title | Description |
|---|---|---|
| BG000 | Sunitinib Maintenance Therapy | Sunitinib 50 mg po QD × 28 days followed by a 14 day break every 42 days until disease progression or unacceptable toxicity. Treatment to begin 28-42 days after day 1 of the last cycle of induction chemotherapy to allow confirmation of response or disease stability with chemotherapy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression Free Survival Rate | The proportion of patients who are progression-free at 4 months after starting sunitinib. | All 16 patients enrolled received a median of 4 weeks sunitinib maintenance therapy. 1 patient who discontinued requested no follow up and was censored from survival analysis. All survival endpoints were analyzed using the Kaplan-Meier method (Kaplan El, Meier P, Non-parametric Estimation from Incomplete Observations, J Am Stat Association, 1958) | Posted | Number | 95% Confidence Interval | percentage of patients with PFS | 4 Months Post Treatment |
|
Participants were evaluated for toxicity if they received sunitinib maintenance therapy (at least one dose) from onset of this therapy until the participant ended participation.
Treatment was held for Participants with grade 4 hematologic or grade 3-4 non-hematologic toxicities until resolution to grade 2 or less. Treatment was then restarted at a dose of 3.75 mg. A second dose reduction to 25 mg was permitted. Treatment discontinued for a third dose reduction or life-threatening, irreversible or unacceptable toxicity.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sunitinib Maintenance Therapy | Sunitinib 50 mg po QD × 28 days followed by a 14 day break every 42 days until disease progression or unacceptable toxicity. Treatment to begin 28-42 days after day 1 of the last cycle of induction chemotherapy to allow confirmation of response or disease stability with chemotherapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) |
The trial was to be terminated at stage 1 if less than, or equal to, 8 patients were progression free at 4 months. The PFS rate did not reach the threshold required for study continuation and, therefore, the study was discontinued early.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gregory Kalemkerian, M.D. | University of Michigan | (734) 936-4991 | kalemker@umich.edu |
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| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D000077210 | Sunitinib |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| up to 4 months post treatment |
| Percent of Patients With an Objective Response | Scans were performed every 2 cycles to evaluate for response/progression. Response was assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Patients would be considered to have an objective response if they experience CR (Complete Response - Disappearance of all clinical and radiological evidence of target lesions and/or non-target lesions) or PR (Partial Response - A 30% or greater decrease in the sum of LD of all lesions in reference to the baseline sum LD). | 12 weeks (2 cycles) |
| Number of Patients That Discontinue Drug Due to Toxicity | Tolerability of Sunitinib will be evaluated by looking at the number of participants who discontinue drug due to toxicity. Toxicity was graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v.3.0. In the event of any CTC, version 3.0 drug-related grade 3 or 4 non-hematologic or grade 4 hematologic adverse event(s), drug should be held until the toxicity resolves to < grade 1 and then the drug should be restarted at a one dose-level reduction. Recovery to acceptable levels of toxicity must occur within 4 weeks to allow continuation in the study. No more than 2 dose reductions are permitted for any patient. If further dose reduction is required, the patient must be removed from the study. | 20 weeks |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Response to induction chemotherapy | Per response evaluation criteria in Solid Tumors Criteria (RECIST v. 1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR) >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Number | participants |
|
| Performance status | The "Zubrod Performance Scale" is a measure of a lung cancer patient's functionality and condition. The measure ranks patients on a scale from 0-5, with 0 being fully active and asymptomatic, 1 being symptomatic but completely ambulatory, 2 being symptomatic and 50% in bed during day, 3 being symptomatic and more than 50% in bed, but not bedbound; 4 being bedbound or completely disabled; and 5 being moribund. | Number | participants |
|
|
|
| Secondary | Median Overall Survival | Survival will be defined as the time from the first day of therapy to the date of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. Survival for induction therapy will be calculated from day 1 of first cycle of chemotherapy. Survival for post-induction therapy will be calculated from the date the patient starts sunitinib. | 15 participants in Sunitinib maintenance therapy (main study) were enrolled and were evaluable for this outcome measure. Although 16 patients were enrolled, one patient opted to discontinue therapy, refused further follow-up, and was therefore censored from survival analysis. | Posted | Median | 95% Confidence Interval | months | up to 4 months post treatment |
|
|
|
| Secondary | Percent of Patients With an Objective Response | Scans were performed every 2 cycles to evaluate for response/progression. Response was assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Patients would be considered to have an objective response if they experience CR (Complete Response - Disappearance of all clinical and radiological evidence of target lesions and/or non-target lesions) or PR (Partial Response - A 30% or greater decrease in the sum of LD of all lesions in reference to the baseline sum LD). | Patients who received at least 2 cycles of study therapy (maintenance sunitinib) | Posted | Number | percentage of participants | 12 weeks (2 cycles) |
|
|
|
| Secondary | Number of Patients That Discontinue Drug Due to Toxicity | Tolerability of Sunitinib will be evaluated by looking at the number of participants who discontinue drug due to toxicity. Toxicity was graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v.3.0. In the event of any CTC, version 3.0 drug-related grade 3 or 4 non-hematologic or grade 4 hematologic adverse event(s), drug should be held until the toxicity resolves to < grade 1 and then the drug should be restarted at a one dose-level reduction. Recovery to acceptable levels of toxicity must occur within 4 weeks to allow continuation in the study. No more than 2 dose reductions are permitted for any patient. If further dose reduction is required, the patient must be removed from the study. | All patients who received sunitinib maintenance therapy were evaluable for toxicity and tolerability analysis. | Posted | Number | participants | 20 weeks |
|
|
|
| 4 |
| 16 |
| 16 |
| 16 |
| Abdominal pain | Gastrointestinal disorders | CTCAE (3.0) |
|
| Alanine aminotransferase increased | Metabolism and nutrition disorders | CTCAE (3.0) |
|
| Alkaline phosphatase increased | Metabolism and nutrition disorders | CTCAE (3.0) |
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| Aspartate aminotransferase increased | Metabolism and nutrition disorders | CTCAE (3.0) |
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| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) |
|
| Cardiac ischemia/infarction | Cardiac disorders | CTCAE (3.0) |
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| Cardiopulmonary arrest | Cardiac disorders | CTCAE (3.0) |
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| Chest pain | Cardiac disorders | CTCAE (3.0) |
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| Confusion | Psychiatric disorders | CTCAE (3.0) |
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| Death | General disorders | CTCAE (3.0) |
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| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) |
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| Fatigue | General disorders | CTCAE (3.0) |
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| Hypertension | Vascular disorders | CTCAE (3.0) |
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| Infection, Lung (pneumonia) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) |
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| Pain in extremity | General disorders | CTCAE (3.0) |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) |
|
| Ataxia | Nervous system disorders | CTCAE (3.0) |
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| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) |
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| Bruising | Injury, poisoning and procedural complications | CTCAE (3.0) |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) |
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| Decubitus | Skin and subcutaneous tissue disorders | CTCAE (3.0) |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) |
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| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) |
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| Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) |
|
| Edema limbs | General disorders | CTCAE (3.0) |
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| Fatigue | General disorders | CTCAE (3.0) |
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| Hand-and-foot syndrome | Skin and subcutaneous tissue disorders | CTCAE (3.0) |
|
| Headache | Nervous system disorders | CTCAE (3.0) |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) |
|
| Hypertension | Vascular disorders | CTCAE (3.0) |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) |
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| Insomnia | Psychiatric disorders | CTCAE (3.0) |
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| Joint pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) |
|
| Leukocytes | Blood and lymphatic system disorders | CTCAE (3.0) |
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| Mucositis oral | Gastrointestinal disorders | CTCAE (3.0) |
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| Muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (3.0) |
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| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (3.0) |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) |
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| Neutrophils | Blood and lymphatic system disorders | CTCAE (3.0) |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (3.0) |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE (3.0) |
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| Platelet count decreased | Blood and lymphatic system disorders | CTCAE (3.0) |
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| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) |
|
| Rash desquamating | Skin and subcutaneous tissue disorders | CTCAE (3.0) |
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| Skin disorder | Skin and subcutaneous tissue disorders | CTCAE (3.0) |
|
| Speech disorder | Nervous system disorders | CTCAE (3.0) |
|
| Sweating | Skin and subcutaneous tissue disorders | CTCAE (3.0) |
|
| Taste alteration | Gastrointestinal disorders | CTCAE (3.0) |
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| Urine discoloration | Renal and urinary disorders | CTCAE (3.0) |
|
| Voice alteration | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) |
|
| Weight loss | Investigations | CTCAE (3.0) |
|
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| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |