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

NCT ID: NCT01344824

Last Updated: 2017-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2016-07-20

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.

Conditions

Lung Cancer

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm Trial

Bevacizumab, Carboplatin, and Pemetrexed disodium, with option for second line erlotinib hydrochloride

Group Type: OTHER

bevacizumab

Intervention Type: BIOLOGICAL

15 mg/kg once per 21 day cycle (up to 4 cycles).

carboplatin

Intervention Type: DRUG

Area Under the Curve (AUC)=6, once every 21 day cycle (up to 4 cycles)

erlotinib hydrochloride

Intervention Type: DRUG

150mg, daily for 21 day cycle (up to 4 cycles)

pemetrexed disodium

Intervention Type: DRUG

500 mg/m2 on day 1 of a 21 day cycle (up to 4 cycles)

Interventions

bevacizumab

15 mg/kg once per 21 day cycle (up to 4 cycles).

Intervention Type: BIOLOGICAL

carboplatin

Area Under the Curve (AUC)=6, once every 21 day cycle (up to 4 cycles)

Intervention Type: DRUG

erlotinib hydrochloride

150mg, daily for 21 day cycle (up to 4 cycles)

Intervention Type: DRUG

pemetrexed disodium

500 mg/m2 on day 1 of a 21 day cycle (up to 4 cycles)

Intervention Type: DRUG

Other Intervention Names

Avastin; Paraplatin; Tarceva; ALIMTA

Eligibility Criteria

Inclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas E. Stinchcombe, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Mission Hospital

Asheville, North Carolina, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

CCHC New Bern Cancer Care

New Bern, North Carolina, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 26774201 (View on PubMed)

Related Links

http://unclineberger.org

UNC Lineberger Comprehensive Cancer Center

Other Identifiers

P30CA016086

Identifier Type: NIH

Identifier Source: secondary_id

View Link

LCCC 0825

Identifier Type: -

Identifier Source: org_study_id