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 ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00698815
First received: June 14, 2008
Last updated: September 24, 2014
Last verified: July 2014
  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. 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.


Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: pemetrexed disodium
Drug: sunitinib malate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib (NSC # 736511) or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 18 week progression-free survival (PFS) rate [ Time Frame: At 18 weeks ] [ Designated as safety issue: No ]
    The 18 week progression-free survival rate was defined as the proportion of patients that were alive and progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.


Secondary Outcome Measures:
  • PFS [ Time Frame: Time from randomization to disease progression and death of any cause, whichever comes first (up to 3 years) ] [ Designated as safety issue: No ]
    PFS was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.

  • Overall response rate [ Time Frame: Duration of treatment (up to 3 years) ] [ Designated as safety issue: No ]

    The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. An exact binomial confidence interval will be computed for these estimates.

    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.


  • Overall survival (OS) [ Time Frame: Time from randomization to death (up to 3 years) ] [ Designated as safety issue: No ]
    OS is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.


Other Outcome Measures:
  • Degree of change in VEGF concentrations induced by sunitinib malate [ Time Frame: Baseline to up to 6 weeks ] [ Designated as safety issue: No ]
    Investigated using a two-way analysis of variance model.

  • Mean change in tumor size [ Time Frame: Baseline to 6 weeks ] [ Designated as safety issue: No ]
    Association with PFS assessed using the rank-covariance statistic.


Enrollment: 130
Study Start Date: April 2008
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (pemetrexed)
Patients receive pemetrexed disodium 500 mg/m^2 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
Other Names:
  • ALIMTA
  • LY231514
  • MTA
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (sunitinib)
Patients receive sunitinib malate at 37.5 mg PO QD 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 PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (pemetrexed and sunitinib)
Patients receive pemetrexed disodium 500 mg/m^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD 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
Other Names:
  • ALIMTA
  • LY231514
  • MTA
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the 18 week progression-free survival rate of pemetrexed (pemetrexed disodium) alone (Arm I), sunitinib (sunitinib malate) alone (Arm II) and pemetrexed plus sunitinib (Arm III) in the second-line setting of advanced non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To compare the progression-free survival of the three arms. II. To estimate the response rate, duration of response, rate of stable disease, overall survival and to characterize the toxicity profiles of the three arms.

III. To estimate the response rate, duration of response, rate of stable disease, and overall survival and toxicity of sunitinib in those patients on Arm I that receive this regimen in the third line setting.

IV. To assess vascular endothelial growth factor (VEGF) haplotypes in advanced non-small cell lung cancer.

V. To test change in tumor size at 6 weeks (after 2 cycles of therapy, typically the first evaluation point in this type of study) as an early predictor of therapeutic activity in second-line treatment of non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive pemetrexed disodium intravenously (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 sunitinib malate orally (PO) once daily (QD) 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 sunitinib malate PO QD 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 treatment, patients are followed up 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

Inclusion Criteria:

  • Histologic documentation: histologic or cytologic documentation of NSCLC
  • Stage: IIIB/IV with evidence of disease progression following first-line therapy
  • Tumor site: lung (non-small cell)
  • No cavitary lesions
  • Only one prior chemotherapy regimen in the first-line stage IIIB/IV setting is allowed; this could have been either a platinum- or non-platinum-based regimen
  • First-line therapy must be completed >= 28 days before registration
  • Prior adjuvant therapy is allowed provided the patient had one previous regimen in the advanced stage IIIB/IV setting
  • At least 28 days from prior major surgery and at least 14 days from any prior radiotherapy before registration
  • No prior inhibitors of VEGF receptor (VEGFR) (e.g., SU5416, SU6668, AZ6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib); prior treatment with epidermal growth factor receptor (EGFR) inhibitors and bevacizumab is allowed, provided at least 4 weeks has elapsed
  • No prior pemetrexed
  • Patients must have measurable or non-measurable disease

    • Measurable disease

      • Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1 cm with spiral computed tomography (CT) scan
    • Non-measurable disease

      • All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly nonmeasurable lesions
    • Lesions that are considered non-measurable 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Pregnant or nursing mothers are not eligible for this study; patients in their child bearing years must have a baseline negative pregnancy test (in the case of females); males and females must practice appropriate contraceptive measures during the period of protocol therapy and for 6 months after completion of protocol therapy; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives (Norplant), or double barrier method (diaphragm plus condom)
  • No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT interval (QTc interval) > 500 msec (within 2 years prior to registration); the use of agents with proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, flecainide) is not recommended while on protocol therapy
  • Patients with class I New York Heart Association (NYHA) heart failure are eligible; patients with a history of class II NYHA heart failure are eligible, provided they meet at least one of 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 symptomatic congestive heart failure within 12 months prior to entry are not eligible
  • No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident or transient ischemic attack 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 anticoagulation for thromboembolic disease are not eligible; Note: Low doses of coumadin (up to 2 mg daily) are permitted for prophylaxis of thrombosis
  • 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 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
  • Patients with a history of hypothyroidism or hyperthyroidism are eligible, provided they are currently euthyroid
  • None of the following within 28 days of beginning 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 their use is discouraged
  • No symptomatic or untreated central nervous system (CNS) metastases; patients with CNS metastases must be asymptomatic, must have received definitive therapy (>= 6 weeks since resection or >= 2 weeks since radiotherapy) for brain metastases, and be off steroids or on a stable dose for 2 weeks prior to registration
  • No chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal antiinflammatory agents known to inhibit platelet function; treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is not allowed
  • No pleural effusions or ascites that are detectable on physical exam
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00698815

  Show 105 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Rebecca Heist Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00698815     History of Changes
Other Study ID Numbers: NCI-2009-00471, NCI-2009-00471, CALGB-30704, CDR0000589102, CALGB 30704, CALGB-30704, U10CA031946, P30CA014236
Study First Received: June 14, 2008
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Pemetrexed
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014