Cisplatin or Carboplatin, and Etoposide With or Without Sunitinib Malate in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Extensive Stage Lung Small Cell Carcinoma Clinical Trial

Official title:

Combination Chemotherapy With or Without Maintenance Sunitinib Malate (NSC 736511) for Untreated Extensive Stage Small Cell Lung Cancer: A Phase IB/Randomized Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00453154
• Other study ID #: NCI-2009-00465
• Secondary ID: NCI-2009-00465CD
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 15, 2007
• Est. completion date: August 20, 2015

Study information

• Verified date: March 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This partially randomized phase I/II trial studies the side effects and best dose of sunitinib malate and to see how well it works when given together with cisplatin or carboplatin and etoposide in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cisplatin or carboplatin and etoposide are more effective when given with or without sunitinib malate in treating small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

I. To determine the phase II dose for sunitinib (sunitinib malate) combined with cisplatin and etoposide. (Phase IB) II. To compare the progression-free survival of patients with extensive stage small cell lung cancer treated with cisplatin or carboplatin and etoposide followed by maintenance sunitinib to patients receiving the same chemotherapy followed by placebo. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the single agent response rate for sunitinib given as monotherapy after chemotherapy. (Phase II) II. To assess the overall survival of patients treated with cisplatin or carboplatin and etoposide followed by sunitinib. (Phase II) III. To evaluate the toxicity and tolerability of maintenance sunitinib after cisplatin or carboplatin and etoposide. (Phase II) IV. To determine the association between vascular endothelial growth factor (VEGF) plasma levels and tumor response. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of sunitinib malate followed by a randomized phase II study.

PHASE I (close to accrual 5/17/08):

COMBINATION THERAPY: Patients receive cisplatin or carboplatin intravenously (IV) on day 1, etoposide IV on days 1-3, and sunitinib malate orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive sunitinib malate PO alone QD. Treatment continues in the absence of disease progression or unacceptable toxicity.

PHASE II:

COMBINATION THERAPY: Patients receive cisplatin or carboplatin and etoposide as in Phase I. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 3-8 weeks after completion of combination chemotherapy or >= 4 courses of combination therapy, patients with a responding or stable disease are randomized to 1 of 2 treatment arms. All patients must be euthyroid before starting on maintenance therapy.

ARM I: Patients receive sunitinib malate PO QD. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: August 20, 2015
• Est. primary completion date: June 30, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients must have histologically or cytologically documented small cell lung cancer

• Eligible disease stages: the extensive disease classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive stage patients are defined as those patients with extrathoracic metastatic, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy or contralateral hilar adenopathy

• All patients must have measurable disease:

• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan

• Lesions that are considered non-measurable, which would make the patient not eligible, include the following:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• No prior chemotherapy for small cell lung cancer (SCLC)

• Radiation therapy must have been completed at least one week before initiation of protocol therapy

• Common Toxicity Criteria (CTC) performance status:

• Phase IB: 0-1

• Phase II: 0-2

• No "currently active" second malignancy other than non-melanoma skin cancers

• No history of brain metastases, spinal cord compression, or carcinomatous meningitis

• No ongoing cardiac dysrhythmias, atrial fibrillation, or QTc interval >= 500 msec; the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, pedridel, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy

• Patients with class I New York Heart Association (NYHA) are eligible; patients with a history of class II NYHA are eligible, provided they meet the following criteria:

• Patients with a history of class II heart failure who are asymptomatic on treatment

• Patients with prior anthracycline exposure

• Patients who have received central thoracic radiation that included the heart in the radiotherapy port

• Patients with a history of class III or IV NYHA heart failure within 12 months prior to registration are not eligible

• Additionally, no myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident including transient ischemic attack, or pulmonary embolism within the last year

• Patients with hypertension that cannot be controlled by medications (> 150/100 mmHg despite optimal medical therapy) are not eligible

• Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin are excluded, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided the patient's prothrombin time (PT) international normalized ratio (INR) is =< 1.5

• No evidence of hemoptysis within 4 weeks prior to starting study treatment; patients with blood-tinged or blood streaked sputum will be permitted on study if the hemoptysis amounts to less than 5 mL of blood per episode and less than 10 mL of blood per 24-hour period in the best estimate of the investigator

• None of the following within 28 days of treatment: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious or non-healing wound, ulcer, or bone fracture

• The use of the following specific inhibitors and inducers of cytochrome p450, family 3, subfamily A, polypeptide 4 (CYP3A4) is not permitted; the following inhibitors of CYP3A4 are prohibited within 7 days before and during treatment with sunitinib: azole antifungals (ketoconazole, itraconazole), diltiazem, clarithromycin, erythromycin, verapamil, delavirdine, and human immunodeficiency virus (HIV) protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir); the following inducers of CYP3A4 are prohibited within 12 days before beginning and during treatment with sunitinib: rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's Wort, efavirenz, tipranavir

• Other inhibitors and inducers of CYP3A4 may be used if necessary, but there use is discouraged

• Non-pregnant and non-nursing

• Granulocytes >= 1,500/ul

• Platelets >= 100,000/ul

• Creatinine clearance >= 70 ml/min

• Total bilirubin =< 1.5 mg/dl

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (patients w/ liver metastases may have AST/ALT =< 5 x ULN)

• Partial thromboplastin time (PTT) =< 1.5 x ULN

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Small Cell
• Extensive Stage Lung Small Cell Carcinoma
• Recurrent Lung Small Cell Carcinoma
• Small Cell Lung Carcinoma

Intervention

Drug:
• Carboplatin
Given IV
• Cisplatin
Given IV
• Etoposide
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Placebo Administration
Given PO

Drug:
• Sunitinib Malate
Given PO

Locations

Country	Name	City	State
United States	Arroyo Grande Community	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Beaufort Memorial Hospital	Beaufort	South Carolina
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Danville Regional Medical Center	Danville	Virginia
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Valley Medical Oncology Consultants-Fremont	Fremont	California
United States	Florida Cancer Specialists-Gainesville Cancer Center	Gainesville	Florida
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Glens Falls Hospital	Glens Falls	New York
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Jupiter Medical Center	Jupiter	Florida
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Kewanee Hospital	Kewanee	Illinois
United States	Community Howard Regional Health	Kokomo	Indiana
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Nebraska Cancer Research Center	Lincoln	Nebraska
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	El Camino Hospital	Mountain View	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Ralph Lauren Center for Cancer Care and Prevention	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Hematology and Oncology Associates-Oakland	Oakland	California
United States	Highland General Hospital	Oakland	California
United States	Tom K Lee Inc	Oakland	California
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Plasma Levels of VEGF Prior to, During Single-agent, and Following Treatment With Sunitinib Malate	The frequency of tumor response by the optimally dichotomized VEGF levels will be tabulated and their association will be tested by Fisher's exact test as well as the maximally selected rank test. The association of the VEGF levels as continuous predictor with tumor response will be tested by Wilcoxon rank sum test. Further assessments of the association of the VEGF levels as> continuous or binary variables and the tumor response will be implemented in a logistic regression while adjusting for other covariates such as performance status, weight loss and age	Baseline to within 7 days of sunitinib/placebo therapy discontinuation
Other	Change in Plasma Levels of PDGF	Correlated with clinical outcome (response and survival).	Baseline to within 7 days of sunitinib/placebo therapy discontinuation
Primary	Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I)	The maximum tolerated dose is defined at the highest sunitinib dose at which less than one third of participants develop a dose limiting toxicity (DLT). A DLT is defined as: delay of beginning cycle 2 of chemotherapy by > 7 days due to neutropenia, grade 4 hematologic toxicity lasting greater than 1 week (chemotherapy alone would be expected to cause significant grade 4 hematologic toxicity) or grade 3 or 4 nonhematologic toxicity (excluding grade 3 or 4 fatigue if the patient is found to be hypothyroid and responds to fatigue < grade 3 with thyroid replacement therapy).	21 days
Primary	Progression-free Survival (Phase II)	Progression free survival (PFS) was defined as the time from maintenance randomization to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.	Up to 3 years
Secondary	Overall Survival	Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.	Up to 3 years
Secondary	Number of Participants With Overall Tumor Response	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs.	Up to 3 years

External Links

•   Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive