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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00280150
First received: January 19, 2006
Last updated: February 14, 2013
Last verified: February 2013

January 19, 2006
February 14, 2013
January 2006
January 2012   (final data collection date for primary 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]) [ 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 ]
  • To establish the dose of both bevacizumab and erlotinib given concurrently with low-dose weekly carboplatin/paclitaxel and 74 Gy of TCRT
  • To establish the safety and toxicity profile of combining both bevacizumab and erlotinib in combination with carboplatin/paclitaxel with concurrent TCRT
  • Phase I
  • Phase II
  • To evaluate the overall impact of this novel treatment regimen on the progression-free survival in stage IIIA/B NSCLC
  • To evaluate the overall toxicity profile of this regimen in an expanded number of patients treated in a phase II fashion
Complete list of historical versions of study NCT00280150 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Phase I/II
  • To evaluate the response rate and toxicity profile of induction carboplatin/paclitaxel and bevacizumab in stage IIIA/B NSCLC
  • To evaluate the overall response rate and survival profile of this treatment platform in stage IIIA/B NSCLC
  • To establish the feasibility and tolerability of consolidation erlotinib and bevacizumab following combined modality therapy in the stage IIIA/B NSCLC population
Not Provided
Not Provided
 
Combination Chemotherapy, Bev, RT, and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lung Cancer
  • 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 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.
    Interventions:
    • Biological: bevacizumab
    • Drug: carboplatin
    • Drug: paclitaxel
    • Radiation: 3-dimensional conformal radiation therapy
  • 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.
    Interventions:
    • Biological: bevacizumab
    • Drug: carboplatin
    • Drug: erlotinib hydrochloride
    • Drug: paclitaxel
    • Radiation: 3-dimensional conformal radiation therapy
  • 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.
    Interventions:
    • Biological: bevacizumab
    • Drug: carboplatin
    • Drug: erlotinib hydrochloride
    • Drug: paclitaxel
    • Radiation: 3-dimensional conformal radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
January 2013
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00280150
LCCC0511, P30CA016086, UNC IRB 05-2091
Yes
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Thomas Stinchcombe, MD UNC Lineberger Comprehensive Cancer Center
Principal Investigator: Thomas A. Stinchcombe, MD University of North Carolina, Chapel Hill
UNC Lineberger Comprehensive Cancer Center
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP