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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

Phase 2
18 Years
Open (Enrolling)
Lung Cancer

Thank you

Trial Information

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



- 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


- 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

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.

Inclusion Criteria


- 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

- 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


- 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


- 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

- 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

- 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


- 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

- 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)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Description:

Documented radiographic response per RECIST criteria each year, until subject death

Outcome Time Frame:

until death

Safety Issue:


Principal Investigator

Thomas E. Stinchcombe, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:

LCCC 0825



Start Date:

November 2010

Completion Date:

December 2015

Related Keywords:

  • Lung Cancer
  • 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
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
University of Pittsburgh Medical CenterPittsburgh, Pennsylvania  15213
Leo W. Jenkins Cancer Center at ECU Medical SchoolGreenville, North Carolina  27834
Mission HospitalAsheville, North Carolina  28801
CCHC New Bern Cancer CareNew Bern, North Carolina  28562