Combination Chemotherapy, Bevacizumab, Radiation Therapy, 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:	National Cancer Institute (NCI)
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:	Treatment, Non-Randomized, Open Label, Active Control
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 National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of bevacizumab and erlotinib when given together with carboplatin, paclitaxel, and thoracic conformal radiotherapy (Phase I [closed to accrual as of 1/3/2008]) [ 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]) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression-free survival (Phase II) [ Designated as safety issue: No ]
Overall toxicity profile (Phase II) [ Designated as safety issue: Yes ]
Response rate to induction therapy (Phase I [closed to accrual as of 1/3/2008] and II) [ Designated as safety issue: No ]
Toxicity profile of induction therapy (Phase I [closed to accrual as of 1/3/2008] and II) [ Designated as safety issue: Yes ]
Overall response rate and survival profile (Phase I [closed to accrual as of 1/3/2008] and II) [ 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) [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	January 2006

Arms	Assigned Interventions
Cohort 1: Experimental 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
Cohort 2: Experimental 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
Cohort 3: Experimental 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

Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of bevacizumab and erlotinib hydrochloride when given together with carboplatin, paclitaxel, and thoracic conformal radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer. (Phase I [closed to accrual as of 1/3/2008])
Determine the safety and toxicity profile of this regimen in these patients. (Phase I [closed to accrual as of 1/3/2008])
Determine the progression-free survival of patients treated with induction therapy comprising carboplatin, paclitaxel, and bevacizumab followed by chemoradiotherapy comprising thoracic conformal radiotherapy, carboplatin, paclitaxel, bevacizumab, and erlotinib hydrochloride and consolidation therapy comprising bevacizumab and erlotinib hydrochloride. (Phase II)
Determine the overall toxicity profile of this regimen in these patients. (Phase II)

Secondary

Determine the response rate in patients treated with induction therapy comprising carboplatin, paclitaxel, and bevacizumab. (Phase I[closed to accrual as of 1/3/2008] and II)
Determine the toxicity profile of induction therapy in these patients. (Phase I [closed to accrual as of 1/3/2008] and II)
Determine the overall response rate and survival profile in patients treated with this regimen. (Phase I [closed to accrual as of 1/3/2008] and II)
Determine the feasibility and tolerability of administering consolidation therapy comprising erlotinib hydrochloride and bevacizumab after treatment with combined modality therapy (induction therapy and chemoradiotherapy) in these patients. (Phase I [closed to accrual as of 1/3/2008] and II)
Collect tumor and blood samples from these patients for future analysis of correlation between molecular markers and clinical benefit. (Phase I [closed to accrual as of 1/3/2008] and II)

OUTLINE: This is a nonrandomized, open-label, controlled, phase I (closed to accrual as of 1/3/2008), dose-escalation study of bevacizumab and erlotinib hydrochloride, followed by a phase II study.

Phase I (closed to accrual as of 1/3/2008):
- Induction therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients with stable or responding disease proceed to chemoradiotherapy.
- Chemoradiotherapy: Patients receive chemoradiotherapy according to their assigned dose cohort:
  - 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.
  - 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.
  - 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.

Cohorts of 5 patients receive chemoradiotherapy as described above until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 (with grade 4 toxicity) or 3 (with grade 3 toxicity) of 5 patients experience dose-limiting toxicity.

Three to 6 weeks after completion of chemoradiotherapy, patients proceed to consolidation therapy.

Consolidation therapy: Patients receive bevacizumab IV on day 1 and oral erlotinib hydrochloride on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Phase II:
Induction therapy: Patients receive induction therapy as in phase I (closed to accrual as of 1/3/2008).
Chemoradiotherapy: Patients undergo TCRT and receive carboplatin and paclitaxel as in phase I (closed to accrual as of 1/3/2008). Patients also receive bevacizumab and erlotinib hydrochloride as in phase I (closed to accrual as of 1/3/2008) at the MTD/drug combination determined in phase I (closed to accrual as of 1/3/2008).
Consolidation therapy: Patients receive consolidation therapy as in phase I (closed to accrual as of 1/3/2008).

Tumor tissue and peripheral blood is collected at baseline for future correlative and biomarker studies.

After completion of study therapy, patients are followed every 2 months for 2 years, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

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
Batte Cancer Center at Northeast Medical Center	Recruiting
CONCORD, North Carolina, United States, 28025
Contact: Contact Person 704-783-1322
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; 919-966-4432
Wake Forest University Comprehensive Cancer Center	Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive 336-713-6771

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	David Morris, MD	UNC Lineberger Comprehensive Cancer Center
Investigator:	Mark A. Socinski, MD	UNC Lineberger Comprehensive Cancer Center

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

Study ID Numbers:	CDR0000550142, UNC-LCCC-0511
Study First Received:	January 19, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00280150 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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:

Thoracic Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Protein Kinase Inhibitors
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Erlotinib
Respiratory Tract Neoplasms
Neoplasms by Histologic Type

Growth Substances
Mitosis Modulators
Enzyme Inhibitors
Carboplatin
Antimitotic Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Paclitaxel
Lung Diseases
Tubulin Modulators
Carcinoma, Non-Small-Cell Lung
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009