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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01344824
First received: April 28, 2011
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Biological: bevacizumab
Drug: carboplatin
Drug: erlotinib hydrochloride
Drug: pemetrexed disodium
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: until death ] [ Designated as safety issue: No ]
    Documented radiographic response per RECIST criteria each year, until subject death


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Radiographic tumor response assessed by RECIST criteria.

  • Subjects experiencing toxicity [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Toxicity will be evaluated using CTCAE criteria, version 3.


Estimated Enrollment: 40
Study Start Date: November 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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)
    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
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., KRAS and 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 CNS 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 CNS metastases treated by neurosurgical resection
    • No brain biopsy within the past 3 months

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • 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)
  • AST/ALT ≤ 2.5 times ULN
  • Calculated creatinine clearance > 45 mL/min OR creatinine ≤ 1.5 times ULN
  • PT/INR ≤ 1.5 times ULN
  • PTT ≤ 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-VEGF 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)
  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: NCT01344824

Contacts
Contact: Donna Rowe, RN (919) 966-7359 donna_rowe@med.unc.edu

Locations
United States, North Carolina
Mission Hospital Active, not recruiting
Asheville, North Carolina, United States, 28801
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7295
Contact: Clinical Trials Office - Lineberger Comprehensive Cancer Cente    877-668-0683      
Leo W. Jenkins Cancer Center at ECU Medical School Withdrawn
Greenville, North Carolina, United States, 27834
CCHC New Bern Cancer Care Active, not recruiting
New Bern, North Carolina, United States, 28562
United States, Pennsylvania
University of Pittsburgh Medical Center Active, not recruiting
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Principal Investigator: Thomas E. Stinchcombe, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01344824     History of Changes
Other Study ID Numbers: LCCC 0825, P30CA016086, CDR0000665860
Study First Received: April 28, 2011
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer

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

ClinicalTrials.gov processed this record on September 22, 2014