Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy, Bevacizumab, Radiation Therapy, and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Active	18 and over	NCI	UNC-LCCC-0511 LCCC 0511, NCT00280150

Objectives

Primary

1. 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])
2. Determine the safety and toxicity profile of this regimen in these patients. (Phase I [closed to accrual as of 1/3/2008])
3. 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)
4. Determine the overall toxicity profile of this regimen in these patients. (Phase II)

Secondary

1. 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)
2. Determine the toxicity profile of induction therapy in these patients. (Phase I [closed to accrual as of 1/3/2008] and II)
3. 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)
4. 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)
5. 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)

Entry 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

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

Patient Characteristics:

• ECOG performance status 0-1
• Hemoglobin ≥ 9.0 mg/dL
• Platelet count ≥ 100,000/mm³
• ANC ≥ 1,500/mm³
• FEV₁ ≥ 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

Expected Enrollment

Outcomes

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])
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])

Progression-free survival (Phase II)
Overall toxicity profile (Phase II)
Response rate to induction therapy (Phase I [closed to accrual as of 1/3/2008] and II)
Toxicity profile of induction therapy (Phase I [closed to accrual as of 1/3/2008] and II)
Overall response rate and survival profile (Phase I [closed to accrual as of 1/3/2008] and II)
Feasibility and tolerability of administering consolidation therapy after induction therapy and chemoradiotherapy (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.

Trial Contact Information

Trial Lead Organizations

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

David Morris, MD, Principal investigator		Ph: 919-966-7700
Mark Socinski, MD, Protocol co-chair		Ph: 919-966-4431 Email: socinski@med.unc.edu

U.S.A.
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Clinical Trials Office - Lineberger Comprehensive Cancer Center	Ph:  877-668-0683; 919-966-4432
	CONCORD
	Batte Cancer Center at Northeast Medical Center
		Contact Person	Ph:  704-783-1322 800-575-1275
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Clinical Trials Office - Wake Forest University Comprehensive Cancer Center	Ph:  336-713-6771

Registry Information
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
Trial Start Date		2006-01-01
Registered in ClinicalTrials.gov		NCT00280150
Date Submitted to PDQ		2007-05-04
Information Last Verified		2008-07-27
NCI Grant/Contract Number		CA16086

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