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
  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 1
Phase 2

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:


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 ]

Enrollment: 48
Study Start Date: January 2006
Study Completion Date: January 2013
Primary Completion Date: January 2012 (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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: Thomas Stinchcombe, MD UNC Lineberger Comprehensive Cancer Center
Principal Investigator: Thomas A. Stinchcombe, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
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: February 14, 2013
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:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Bevacizumab
Carboplatin
Erlotinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014