Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Carboplatin, Pemetrexed Disodium, and Bevacizumab for Patients With Stage III or IV Non-Small Cell Lung Cancer Who Are Light/Never Smokers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01344824
Recruitment Status : Completed
First Posted : April 29, 2011
Results First Posted : July 11, 2017
Last Update Posted : October 30, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE April 28, 2011
First Posted Date  ICMJE April 29, 2011
Results First Submitted Date  ICMJE May 2, 2017
Results First Posted Date  ICMJE July 11, 2017
Last Update Posted Date October 30, 2017
Study Start Date  ICMJE March 2010
Actual Primary Completion Date May 24, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2017)
Progression-free Survival [ Time Frame: 1400 days ]
Documented radiographic response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by imaging: 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. criteria each year, until subject death
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2011)
Progression-free Survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2017)
  • Overall Survival [ Time Frame: 1400 days ]
    Time of enrollment to date of death.
  • Subjects Experiencing Toxicity [ Time Frame: 90 days ]
    Toxicity will be evaluated using CTCAE criteria, version 3, all grade 3 and 4 events.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2011)
  • Overall Survival
  • Toxicity using NCI CTCAE version 3.0
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Carboplatin, Pemetrexed Disodium, and Bevacizumab for Patients With Stage III or IV Non-Small Cell Lung Cancer Who Are Light/Never Smokers
Official Title  ICMJE A Multicenter Phase II Trial of Carboplatin, Pemetrexed, and Bevacizumab Followed By Pemetrexed and Bevacizumab Maintenance Therapy in Patients With a Light or Never Smoking History
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Giving carboplatin and pemetrexed disodium together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin and pemetrexed disodium together with bevacizumab works in treating patients with stage III or stage IV non-small cell lung cancer who are light or never smokers.

Detailed Description

OBJECTIVES:

Primary

  • To estimate the progression-free survival (PFS) of patients with advanced non-small cell lung cancer who are never or light smokers treated with carboplatin, pemetrexed disodium, and bevacizumab followed by pemetrexed disodium and bevacizumab maintenance therapy.

Secondary

  • To estimate the overall survival (OS) of patients treated with this regimen.
  • To estimate the toxicity of treatment using the NCI CTCAE version 3.0.
  • To conduct an exploratory analysis of molecular markers, e.g., Kirsten rat sarcoma (KRAS) and epidermal growth factor receptor (EGFR) mutations, in patients with a never or light smoking history and to analyze any potential association with response, PFS, and OS.
  • To assess response to second-line erlotinib hydrochloride therapy according to RECIST criteria.

OUTLINE: This is a multicenter study.

  • First-line therapy: Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve partial or complete response or have stable disease progress to maintenance therapy.
  • Maintenance therapy: Patients receive pemetrexed disodium IV over 10 minutes and bevacizumab IV over 30 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients who experience disease progression or unacceptable toxicity may receive second-line therapy with erlotinib hydrochloride as part of standard-of-care treatment.

Tissue samples are collected at baseline for laboratory biomarker analysis.

After completion of maintenance therapy, patients are followed every 4 weeks for 2 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • Biological: bevacizumab
    15 mg/kg once per 21 day cycle (up to 4 cycles).
    Other Name: Avastin
  • Drug: carboplatin
    Area Under the Curve (AUC)=6, once every 21 day cycle (up to 4 cycles)
    Other Name: Paraplatin
  • Drug: erlotinib hydrochloride
    150mg, daily for 21 day cycle (up to 4 cycles)
    Other Name: Tarceva
  • Drug: pemetrexed disodium
    500 mg/m2 on day 1 of a 21 day cycle (up to 4 cycles)
    Other Name: ALIMTA
Study Arms  ICMJE Single Arm Trial
Bevacizumab, Carboplatin, and Pemetrexed disodium, with option for second line erlotinib hydrochloride
Interventions:
  • Biological: bevacizumab
  • Drug: carboplatin
  • Drug: erlotinib hydrochloride
  • Drug: pemetrexed disodium
Publications * Weiss JM, Villaruz LC, O'Brien J, Ivanova A, Lee C, Olson JG, Pollack G, Gorman R, Socinski MA, Stinchombe TE. Results of a Phase II Trial of Carboplatin, Pemetrexed, and Bevacizumab for the Treatment of Never or Former/Light Smoking Patients With Stage IV Non-Small Cell Lung Cancer. Clin Lung Cancer. 2016 Mar;17(2):128-32. doi: 10.1016/j.cllc.2015.12.006. Epub 2015 Dec 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 7, 2017)
38
Original Estimated Enrollment  ICMJE
 (submitted: April 28, 2011)
40
Actual Study Completion Date  ICMJE July 20, 2016
Actual Primary Completion Date May 24, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary lung carcinoma

    • Non-squamous histology
    • Advanced disease defined as stage IIIB disease with cytologically documented malignant pleural or pericardial effusion or stage IV disease
  • Available pathology block or unstained slides from initial or subsequent diagnosis

    • Must have undergone ≥ 1 core biopsy
    • No patients whose diagnosis was made through a fine-needle aspirate
  • No uncontrolled pleural effusions, ascites, or third-space fluid collections
  • Meets 1 of the following criteria:

    • Non-smoker, defined as patients who smoked ≤ 100 cigarettes in their lifetime
    • Former light smoker, defined as patients who smoked between > 100 cigarettes AND ≤ 10 pack-years AND quit ≥ 1 year ago
  • No known central nervous system disease, except for treated brain metastases meeting the following criteria:

    • No evidence of progression or hemorrhage after treatment
    • No ongoing requirement for dexamethasone as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period
    • Stable doses of anticonvulsants are allowed
    • Treatment for brain metastases may include whole-brain radiotherapy, radiosurgery (gamma knife, LINAC, or equivalent), or a combination as deemed appropriate by the treating physician
    • No patients with central nervous system (CNS) metastases treated by neurosurgical resection
    • No brain biopsy within the past 3 months

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST/ALT) ≤ 2.5 times ULN
  • Calculated creatinine clearance > 45 mL/min OR creatinine ≤ 1.5 times ULN
  • Prothrombin time ≤ 1.5 times ULN
  • Partial thromboplastin time ≤ ULN
  • Urine protein:creatinine ratio ≤ 1.0
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients with a history of hypertension are eligible provided it is well controlled (BP < 150/100 mm Hg) on a stable regimen of antihypertensive therapy

    • No history of hypertensive crisis or hypertensive encephalopathy
  • Able and compliant with folic acid and B12 supplementation
  • Able to swallow tablets intact or dissolved in water
  • No dysphagia or active gastrointestinal (GI) disease or disorder that alters GI motility or absorption
  • No lack of integrity of the GI tract (e.g., a significant surgical resection of the stomach or small bowel)
  • No abdominal fistula, GI perforation, or intraabdominal abscess within the past 6 months
  • None of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure (NYHA class II-IV)
    • Cardiac arrhythmia
    • Psychiatric illness, social situations, or any other medical condition that would limit compliance with study requirements
  • No myocardial infarction or other evidence of arterial thrombotic disease (angina) within the past 6 months
  • No history of cerebral vascular accident or transient ischemic attack within the past 6 months
  • No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months
  • No history of bleeding diathesis or coagulopathy
  • No ongoing hemoptysis, defined as ≥ ½ teaspoon of bright red blood

    • Patients with procedure-related hemoptysis that has resolved post-procedure are eligible
  • No serious nonhealing wound, ulcer, bone fracture, or significant traumatic injury within the past 28 days
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy

    • Patient must be chemotherapy naive
    • Prior neoadjuvant or adjuvant chemotherapy allowed provided it was completed ≥ 6 months ago
  • No prior anti-vascular endothelial growth factor therapy
  • At least 3 weeks since prior major surgery
  • At least 1 week since prior radiotherapy
  • More than 28 days since prior and no concurrent treatment with an investigational agent
  • More than 7 days since prior core biopsy
  • Concurrent daily treatment with aspirin or NSAIDs are eligible provided patients are able to interrupt NSAIDs 2 days before (5 days for long-acting NSAIDs), the day of, and for 2 days following the administration of pemetrexed disodium
  • No concurrent treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01344824
Other Study ID Numbers  ICMJE LCCC 0825
P30CA016086 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party UNC Lineberger Comprehensive Cancer Center
Study Sponsor  ICMJE UNC Lineberger Comprehensive Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Thomas E. Stinchcombe, MD Duke University
PRS Account UNC Lineberger Comprehensive Cancer Center
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP