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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Lung Cancer

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Observed progression-free survival rate

Safety Issue:

Yes

Principal Investigator

Thomas Stinchcombe, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

LCCC0511

NCT ID:

NCT00280150

Start Date:

January 2006

Completion Date:

January 2013

Related Keywords:

  • Lung Cancer
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • recurrent non-small cell lung cancer
  • squamous cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Batte Cancer Center at Northeast Medical CenterConcord, North Carolina  28025