Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), February 2009
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00698815
Purpose
RATIONALE: Drugs used in chemotherapy, such as pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib 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. Giving pemetrexed together with sunitinib may kill more tumor cells. It is not yet known whether pemetrexed and sunitinib are more effective when given alone or together in treating non-small cell lung cancer.
PURPOSE: This randomized phase II trial is studying pemetrexed and sunitinib to compare how well they work when given alone or together as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.
Condition Intervention Phase
Lung Cancer
Drug: pemetrexed disodium
Drug: sunitinib malate
Phase II
MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Sunitinib Sunitinib malate Pemetrexed disodium Pemetrexed Malic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib (NSC # 736511, IND # 74019) or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-Small Cell Lung Cancer
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
18-week progression-free survival rate [ Designated as safety issue: No ]
Secondary Outcome Measures:
Progression-free survival [ Designated as safety issue: No ]
Response rate, duration of response, rate of stable disease, and overall survival [ Designated as safety issue: No ]
Toxicity profile [ Designated as safety issue: Yes ]
Changes in tumor size at 6 weeks as an early predictor of therapeutic activity of pemetrexed disodium and/or sunitinib malate as second-line treatment for non-small cell lung cancer [ Designated as safety issue: No ]
Estimated Enrollment: 225
Study Start Date: April 2008
Estimated Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in arm II as third-line therapy. Drug: pemetrexed disodium
Given IV
Arm II: Experimental
Patients receive oral sunitinib malate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in arm I as third-line therapy. Drug: sunitinib malate
Given orally
Arm III: Experimental
Patients receive pemetrexed disodium IV over 10 minutes on day 1 and oral sunitinib malate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician. Drug: pemetrexed disodium
Given IV
Drug: sunitinib malate
Given orally
Detailed Description:
OBJECTIVES:
Primary
To compare the 18-week progression-free survival rate in patients with stage IIIB or IV non-small cell lung cancer treated with pemetrexed disodium alone vs sunitinib malate alone vs pemetrexed disodium in combination with sunitinib malate as second-line therapy.
Secondary
To compare the progression-free survival of patients treated with these regimens.
To compare the response rate, duration of response, rate of stable disease, and overall survival of patients treated with these regimens.
To characterize the toxicity profiles of these regimens in these patients.
To determine the response rate, duration of response, rate of stable disease, and overall survival of patients who receive sunitinib malate in the third-line setting.
To assess the toxicity of sunitinib malate when administed in the third-line setting in these patients.
To test changes in tumor size at 6 weeks as an early predictor of therapeutic activity of these second-line treatment regimens.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), disease stage (IIIB vs IV), and gender. Patients are randomized to 1 of 3 treatment arms.
Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in arm II as third-line therapy.
Arm II: Patients receive oral sunitinib malate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in arm I as third-line therapy.
Arm III: Patients receive pemetrexed disodium IV over 10 minutes on day 1 and oral sunitinib malate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
After completion of study therapy, patients are followed every 6 weeks until disease progression and then every 6 months for 2 years.
Eligibility
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
Stage IIIB or IV disease
Must have evidence of disease progression after first-line therapy
Measurable or non-measurable disease
Measurable disease is defined as lesions that can be accurately measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan
Non-measurable disease is defined as all other lesions, including small lesions (i.e., longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT scan) and truly non-measurable lesions, including any of the following:
Bone lesions
Leptomeningeal disease
Ascites
Pleural or pericardial effusion
Lymphangitis cutis or pulmonis
Abdominal mass that are not confirmed and followed by imaging techniques
Cystic lesions
No cavitary lesions
No pleural effusions or ascites detectable on physical exam
No symptomatic or untreated CNS metastases
Patients with CNS metastases are eligible provided the metastases were definitively treated with surgery or radiotherapy AND patient is asymptomatic and off steroids or on a stable dose of steroids for 2 weeks prior to study entry
Concurrent enrollment on CALGB-580702 (imaging study) required
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
Granulocytes ≥ 1,500/μL
Platelet count ≥ 100,000/μL
Magnesium ≥ lower limit of normal
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
PTT ≤ 1.5 times ULN
INR ≤ 1.5
Creatinine clearance ≥ 45 mL/min
Quantitative urine protein < 30 mg/dL OR ≤ 1+ on dipstick
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study therapy
QTc interval ≤ 500 msec
No ongoing cardiac dysrhythmias
No atrial fibrillation
No symptomatic congestive heart failure within the past 12 months
NYHA class I heart failure allowed
Patients with a history of NYHA class II heart failure are eligible provided at least 1 of the following criteria is met:
Asymptomatic on treatment
Previously treated with anthracycline
Previously treated with central thoracic radiotherapy that included the heart in the radiotherapy port
No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident, or transient ischemic attack within the past year
No hypertension that cannot be controlled by medications (i.e., blood pressure > 150/100 mm Hg despite optimal medical therapy)
No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome
No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis
Patients with blood-tinged or blood-streaked sputum are eligible provided the hemoptysis is < 5 mL of blood per episode and < 10 mL of blood per 24-hour period, in the best estimate of the investigator
No interstitial pneumonitis or pulmonary fibrosis on baseline CT scan
No abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or serious or non-healing wound, ulcer, or bone fracture within the past 28 days
History of hypothyroidism allowed provided patient is currently euthyroid
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
At least 28 days since prior first-line therapy
No more than one prior chemotherapy regimen (platinum or non-platinum based) in the first-line setting for NSCLC
Prior adjuvant therapy allowed provided the patient received one regimen in the advanced setting
At least 4 weeks since prior EGFR inhibitors or bevacizumab
At least 28 days since prior major surgery (6 weeks since resection of brain metastases)
At least 14 days since prior radiotherapy
More than 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
Azole antifungals (e.g., ketoconazole or itraconazole)
Diltiazem
Clarithromycin
Erythromycin
Verapamil
Delavirdine
HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)
More than 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
Rifampin
Rifabutin
Carbamazepine
Phenobarbital
Phenytoin
St. John's wort
Efavirenz
Tipranavir
No prior pemetrexed disodium
No prior VEGFR inhibitors (e.g., semaxanib, SU6668, AZ6474, sunitinib malate, vatalanib, cediranib, AEE-788, or sorafenib)
No concurrent chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function
No concurrent dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal)
No concurrent therapeutic anticoagulation for thromboembolic disease
Concurrent low-dose warfarin (≤ 2 mg/day) allowed for prophylaxis of thrombosis
No concurrent agents with proarrhymthic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, bepridel, haloperidol, risperidone, indapamide, or flecainide)
No concurrent hormonal therapy, except steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or dexamethasone used intermittently as an antiemetic or as premedication for pemetrexed disodium
No other concurrent chemotherapy
No concurrent palliative radiotherapy
No concurrent G-CSF (filgrastim), GM-CSF (sargramostim), and/or pegfilgrastim
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00698815
Show 64 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
National Cancer Institute (NCI)
Investigators
Study Chair: Mark A. Socinski, MD UNC Lineberger Comprehensive Cancer Center
Investigator: Rebecca S. Heist, MD Harvard School of Public Health
More Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Study ID Numbers: CDR0000589102, CALGB-30704
Study First Received: June 14, 2008
Last Updated: February 7, 2009
ClinicalTrials.gov Identifier: NCT00698815 [history]
Health Authority: Unspecified
Keywords provided by National Cancer Institute (NCI):
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
Study placed in the following topic categories:
Folic Acid
Pemetrexed
Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Sunitinib
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma
Additional relevant MeSH terms:
Respiratory Tract Neoplasms
Neoplasms by Site
Neoplasms
Neoplasms by Histologic Type
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Folic Acid Antagonists
Angiogenesis Inhibitors
Pharmacologic Actions
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
ClinicalTrials.gov processed this record on February 10, 2009
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