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

NCT00280150 | Completed Phase 1 Results DMC

• 2 other identifiers: LCCC 0511UNC IRB 05-2091
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Lung Cancer

Keywords

stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer; squamous cell lung cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Dose of Erlotinib When Given Together With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy (Phase I [Closed to Accrual as of 1/3/2008])

  Dose-limiting toxicities (DLTs) were used to establish which cohort would be used for the phase II portion of the trial. DLTs were defined as any grade 3 or 4 nonhematologic toxicity with the exception of esophagitis, which had to be grade 4; grade 4 neutropenia lasting greater than or equal to 7 days and thrombocytopenia to less than 20,000/microliter.

  6 weeks after completion of therapy

• Safety and Toxicity Profile of Combining Both Bevacizumab and Erlotinib Hydrochloride With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy

  A list of Hematologic and nonhematologic toxicities associated with induction and concurrent therapy. This includes the percentage of patients who experienced grades 2-4 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0).

  6 weeks after completion of therapy

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  5 years

• Response Rate to Induction Therapy (Phase I [Closed to Accrual as of 1/3/2008] and II)

  5 years

• Overall Response Rate and Survival Profile

  5 years

• Feasibility and Tolerability of Administering Consolidation Therapy

  6 cycles

Study Arms (4)

Cohort 1

EXPERIMENTAL

Bevacizumab 10 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)

Biological: bevacizumab; Drug: carboplatin; Drug: paclitaxel; Radiation: 3-dimensional conformal radiation therapy

Cohort 2

EXPERIMENTAL

Bevacizumab 10 mg + Erlotinib 100 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)

Biological: bevacizumab; Drug: carboplatin; Drug: erlotinib hydrochloride; Drug: paclitaxel; Radiation: 3-dimensional conformal radiation therapy

Cohort 3

EXPERIMENTAL

Bevacizumab + Erlotinib 150 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)

Biological: bevacizumab; Drug: carboplatin; Drug: erlotinib hydrochloride; Drug: paclitaxel; Radiation: 3-dimensional conformal radiation therapy

Phase II

EXPERIMENTAL

Bevacizumab + Erlotinib 100 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)

Biological: bevacizumab; Drug: carboplatin; Drug: erlotinib hydrochloride; Drug: paclitaxel; Radiation: 3-dimensional conformal radiation therapy

Interventions

bevacizumab BIOLOGICAL

Given IV

Cohort 1; Cohort 2; Cohort 3; Phase II

carboplatin DRUG

Given IV

Cohort 1; Cohort 2; Cohort 3; Phase II

erlotinib hydrochloride DRUG

Given orally

Cohort 2; Cohort 3; Phase II

paclitaxel DRUG

Given IV

Cohort 1; Cohort 2; Cohort 3; Phase II

3-dimensional conformal radiation therapy RADIATION

Given 5 days a week for 7 weeks

Cohort 1; Cohort 2; Cohort 3; Phase II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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: * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Hemoglobin ≥ 9.0 mg/dL * Platelet count ≥ 100,000/mm³ * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Forced expiratory volume 1 (FEV\_1) ≥ 1 L * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤ 2.5 times ULN * Bilirubin normal * Partial thromboplastin time (PTT) and international normalized ratio (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 New York Heart Association (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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genentech, Inc.: collaborator
• Eli Lilly and Company: collaborator

Study Sites (3)

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

Chapel Hill, North Carolina, 27599-7295, United States

Location

Batte Cancer Center at Northeast Medical Center

Concord, North Carolina, 28025, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Related Publications (1)

• Socinski MA, Stinchcombe TE, Moore DT, Gettinger SN, Decker RH, Petty WJ, Blackstock AW, Schwartz G, Lankford S, Khandani A, Morris DE. Incorporating bevacizumab and erlotinib in the combined-modality treatment of stage III non-small-cell lung cancer: results of a phase I/II trial. J Clin Oncol. 2012 Nov 10;30(32):3953-9. doi: 10.1200/JCO.2012.41.9820. Epub 2012 Oct 8.

  PMID: 23045594 RESULT

Related Links

• UNC Lineberger Comprehensive Cancer Center

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab; Carboplatin; Erlotinib Hydrochloride; Paclitaxel; Radiotherapy, Conformal

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Robin V. Johnson
• Organization: UNC Lineberger Comprehensive Cancer Center

Robin_V_Johnson@med.unc.edu

919-966-1125

Study Officials

• Thomas Stinchcombe, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Thomas A. Stinchcombe, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2006
• First Posted: January 20, 2006
• Study Start: January 1, 2006
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2013
• Last Updated: June 19, 2017
• Results First Posted: June 19, 2017

Record last verified: 2017-05

Locations

US (3)