Combination Chemotherapy, Bev, RT, and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer - Full Text View

Sponsor:	UNC Lineberger Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00280150

Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Radiation therapy uses high energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bevacizumab, radiation therapy, and erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of bevacizumab and erlotinib when given together with combination chemotherapy and radiation therapy and to see how well they work in treating patients with stage III non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Biological: bevacizumab Drug: carboplatin Drug: erlotinib hydrochloride Drug: paclitaxel Radiation: 3-dimensional conformal radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Trial of Induction Carboplatin/Paclitaxel With Bevacizumab Followed by Concurrent Thoracic Conformal Radiation Therapy With Carboplatin/Paclitaxel, Bevacizumab and Erlotinib in Stage IIIA/B Non-Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Paclitaxel Carboplatin Erlotinib hydrochloride Erlotinib Bevacizumab

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum dose of erlotinib when given together with carboplatin, paclitaxel, and thoracic conformal radiotherapy (Phase I [closed to accrual as of 1/3/2008]) [ Time Frame: Observed progression-free survival rate ] [ Designated as safety issue: Yes ]
Safety and toxicity profile of combining both bevacizumab and erlotinib hydrochloride with carboplatin, paclitaxel, and thoracic conformal radiotherapy (Phase I [closed to accrual as of 1/3/2008]) [ Time Frame: Observed progression free survival rate versus a null rate of 50% ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Combination Chemotherapy, Bev, RT, and Erlotinib [ Time Frame: Amount of consolidation erlotinib/bevacizumab subjects receive as well as the toxicities associated with it. ] [ Designated as safety issue: No ]
Overall toxicity profile (Phase II) [ Time Frame: From the start of the treatment until disease progression/recurrence ] [ Designated as safety issue: Yes ]
Response rate to induction therapy (Phase I [closed to accrual as of 1/3/2008] and II) [ Time Frame: Measurement of the longest diameter for all target lesions ] [ Designated as safety issue: No ]
Toxicity profile of induction therapy (Phase I [closed to accrual as of 1/3/2008] and II) [ Time Frame: After establishing the maximum tolerated dose (MTD) of bevacizumab and erlotinib with Cohort 2 ] [ Designated as safety issue: Yes ]
Overall response rate and survival profile (Phase I [closed to accrual as of 1/3/2008] and II) [ Time Frame: Dose of erlotinib established during the phase I portion will be used as the phase II dose in the combined modality therapy ] [ Designated as safety issue: No ]
Feasibility and tolerability of administering consolidation therapy after induction therapy and chemoradiotherapy (Phase I [closed to accrual as of 1/3/2008] and II) [ Time Frame: One year progression free survival (PFS) is 50% ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	January 2006
Estimated Study Completion Date:	January 2017
Estimated Primary Completion Date:	January 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 Patients undergo thoracic conformal radiotherapy (TCRT) on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. Patients also receive carboplatin IV and paclitaxel IV on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43.	Biological: bevacizumab Given IV Drug: carboplatin Given IV Drug: paclitaxel Given IV Radiation: 3-dimensional conformal radiation therapy Given 5 days a week for 7 weeks
Experimental: Cohort 2 Patients undergo TCRT and receive carboplatin, paclitaxel, and bevacizumab as in cohort 1. Patients also receive oral erlotinib hydrochloride on days 2-5, 9-12, 16-19, 23-26, 30-33, 37-40, and 44-47.	Biological: bevacizumab Given IV Drug: carboplatin Given IV Drug: erlotinib hydrochloride Given orally Drug: paclitaxel Given IV Radiation: 3-dimensional conformal radiation therapy Given 5 days a week for 7 weeks
Experimental: Cohort 3 Patients undergo TCRT and receive carboplatin, paclitaxel, and bevacizumab as in cohort 1. Patients also receive higher doses of oral erlotinib hydrochloride on days 2-5, 9-12, 16-19, 23-26, 30-33, 37-40, and 44-47.	Biological: bevacizumab Given IV Drug: carboplatin Given IV Drug: erlotinib hydrochloride Given orally Drug: paclitaxel Given IV Radiation: 3-dimensional conformal radiation therapy Given 5 days a week for 7 weeks

Show Detailed Description

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of non-small cell lung cancer
- Stage IIIA or IIIB disease
- No malignant pleural or pericardial effusions
- No palpable supraclavicular adenopathy
Squamous cell histology allowed provided there is no hemoptysis and no central invasive lesions that abut or invade major blood vessels in the chest (with or without cavitation)
Considered suitable and appropriate for combined modality therapy and thoracic conformal radiotherapy, as determined by the treating medical and radiation oncologist

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Hemoglobin ≥ 9.0 mg/dL
Platelet count ≥ 100,000/mm³
ANC ≥ 1,500/mm³
FEV_1 ≥ 1 L
Creatinine ≤ 1.5 times upper limit of normal (ULN)
AST or ALT ≤ 2.5 times ULN
Bilirubin normal
PTT and INR normal
Urine protein:creatinine ratio < 1.0
Blood pressure ≤ 150/100 mm Hg on 3 separate occasions
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No significant recent hemoptysis (> ½ teaspoon of bright red blood)
No unstable angina
No NYHA congestive heart failure ≥ class II
No myocardial infarction or stroke within the past 6 months
No clinically significant peripheral vascular disease
No evidence of bleeding diathesis or coagulopathy
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No serious, non-healing wound, ulcer, or bone fracture
No thrombosis requiring therapeutic anticoagulation
No significant traumatic injury within the last 28 days

PRIOR CONCURRENT THERAPY:

Recovered from prior surgery
At least 4 weeks since prior and no concurrent participation in another experimental drug study
At least 4 weeks since prior and no concurrent major surgical procedure or open biopsy
At least 2 weeks since prior mediastinoscopy or mediastinotomy
At least 1 week since prior fine needle aspirations or core biopsies
No other concurrent antineoplastic or antitumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00280150

Locations

United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Batte Cancer Center at Northeast Medical Center
Concord, North Carolina, United States, 28025
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	David Morris, MD	UNC Lineberger Comprehensive Cancer Center
Principal Investigator:	David A. Morris, MD	University of North Carolina, Chapel Hill

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	David E. Morris, MD, University of North Carolina at Chapel Hill
ClinicalTrials.gov Identifier:	NCT00280150 History of Changes
Other Study ID Numbers:	LCCC0511, P30CA016086, UNC IRB 05-2091
Study First Received:	January 19, 2006
Last Updated:	March 16, 2011
Health Authority:	United States: Federal Government

Keywords provided by UNC Lineberger Comprehensive Cancer Center:

stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
recurrent non-small cell lung cancer
squamous 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
Carboplatin
Paclitaxel
Erlotinib
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012