A Phase II Study of Neo-Adjuvant Gemcitabine, Cisplatin and Bevacizumab in Stage IIIA (N2) Non-Squamous Cell Non-Small Cell Lung Cancer

NCT00924209 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 09010709-C-0107
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 2

Brief Summary

Background:

• Surgical resection is the treatment of choice for patients with lung cancer, and cure after resection generally depends on whether lymph nodes are involved. A patient with Stage IIIA (N2) lung cancer has cancer in the lymph nodes involving the center of the chest (mediastinum).
• Studies have shown that surgery alone as a treatment for Stage IIIA (N2) lung cancer is not as effective as chemotherapy followed by surgery.
• Giving chemotherapy upfront may prevent the spread of Stage IIIA (N2) lung cancer tumors, and may shrink the tumors to allow adequate surgery to be performed. It is also thought that chemotherapy is usually better tolerated before major surgery than after, so higher doses can be given. Objectives:
• To determine the effectiveness of the combination of three anti-cancer drugs (gemcitabine, cisplatin, and bevacizumab) given before surgery.
• To find out what effects this drug combination may have on the patient and the cancer.
• To determine if the combination of all three drugs given prior to surgery is more effective and as safe, safer, or less safe than other drug combinations given before surgery. Eligibility:
• Patients with Stage IIIA (N2) lung cancer who have not had chemotherapy, radiation, or surgery to treat the cancer. Design:
• Evaluations before the treatment period to determine eligibility:
• Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
• Tests to evaluate heart and lung function, such as an echocardiogram.
• Blood and urine tests.
• Disease evaluation with computed tomography (CT), chest X-ray, positron emission tomography (PET) scans, and bronchoscopy/mediastinoscopy (examinations of the inside of the chest and lungs).
• Treatment with intravenous gemcitabine, cisplatin, and bevacizumab for three 21-day cycles.
• Cycles 1 and 2 - Gemcitabine on day 1 and day 8, cisplatin on day 1, bevacizumab on day 1.
• Cycle 3 - Gemcitabine on day 1 and day 8, cisplatin on day 1 (no bevacizumab).
• Physical examinations and tests will be conducted throughout each cycle.
• Surgery will take place 4 to 6 weeks after the last cycle if heart and lung functions are satisfactory and if the cancer remains stable.
• Chemotherapy (four 21-day cycles of cisplatin and etoposide treatments), further evaluations and examinations, and followup studies will take place 4 to 8 weeks after the surgery.

Conditions

NSCLC; Stage IIIA (N2)

Keywords

Neoadjuvant; Stage IIIA (N2); Cisplatin; Gemcitabine; Bevacizumab; Non-Small Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Rate of Pathologic Complete Response

  Complete response is defined as a disappearance of all target lesions and was assessed by the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

  25 weeks

Secondary Outcomes (4)

• Number of Participants With Serious and Non-Serious Adverse Events

  Date treatment consent signed to date off study, approximately 38 months

• Progression Free Survival (PFS)

  The time between the first day of treatment to the day of disease progression

• Median Survival

  Length of time a participant lives with disease following treatment

• Overall Survival

  The time between the first day of treatment to the day of death

Study Arms (1)

Stage IIIA lung cancer patients

EXPERIMENTAL

Non-squamous cell non small cell lung cancer treated with 1250 mg/m\^2 gemcitabine dose for two doses on day 1 and day 8 every 21 days,80 mg/m\^2 cisplatin day 1 every 21 days for 3 cycles, 7.5 mg/kg bevacizumab on day 1 every 21 days for first 2 cycles only, and 100 mg/m\^2 intravenous, and 100 mg/m\^2 etoposide intravenous per day for consecutive 3 days on days 1 to 3 every 3 weeks for 4 cycles.

Drug: Gemcitabine; Drug: Cisplatin; Drug: Bevacizumab; Procedure: Surgery; Drug: Etoposide

Interventions

Gemcitabine DRUG

1250 mg/m\^2 dose for two doses on days 1 and 8

Also known as: Gemzar

Stage IIIA lung cancer patients

Cisplatin DRUG

80 mg/m\^2 on day 1

Also known as: Cisplatinum

Stage IIIA lung cancer patients

Bevacizumab DRUG

7.5 mg/m\^2 on day 1 every 21 days for first two cycles only

Also known as: Avastin

Stage IIIA lung cancer patients

Surgery PROCEDURE

thoracotomy with lobectomy/pneumonectomy and mediastinal lymph node dissection 4-6 weeks post completion of last cycle of cisplatin

Stage IIIA lung cancer patients

Etoposide DRUG

100 mg/m\^2 intravenous per day for consecutive 3 days on days 1 to 3 every 3 weeks for 4 cycles.

Also known as: Vepesid

Stage IIIA lung cancer patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented non squamous cell non-small cell lung cancer and confirmed by the pathological laboratories at participating centers.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral computed tomography (CT) scan.
• Stage IIIA (N2) disease. All patients will require a baseline mediastinoscopy to ensure histological proof of N2 disease.
• No prior treatment for lung cancer including chemotherapy, radiotherapy, surgery or biological therapy.
• Age greater than or equal to 18 years (males or non-pregnant females).
• Life expectancy of greater than 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky greater than 60 percent).
• Adequate pulmonary and cardiovascular function to tolerate planned surgical resection:
• Pulmonary Function criteria:
• Partial pressure of oxygen (paO2) greater than 65 mmHg, partial pressure of carbon dioxide (paCO2) less than 45 mmHg on room air arterial blood gas (ABG).
• Anticipated post-op forced expiratory volume 1 (FEV1) greater than or equal to 40 percent predicted.
• Anticipated post-op carbon monoxide diffusing capacity (DLCO) greater than or equal to 40 percent predicted.
• If anticipated post-op FEV1 or DLCO less than percent predicted, must have volume of oxygen (VO2) greater than 15ml/kg on oxygen consumption study.
• Cardiac criteria:
• Left ventricular ejection fraction (LVEF) greater than 40 percent.

You may not qualify if:

• Squamous cell cancer or mixed tumors with small cell elements.
• Tumor of any histology in close proximity to a major vessel or cavitation. (Any tumor abutting an interlobar, main pulmonary artery, vena cava or major vein will be excluded).
• History of hemoptysis (bright red blood of one-half teaspoon or more \[greater than or equal to 2.5 mL\] unrelated to any diagnostic procedure. (Patients who have a history of hemoptysis that occurred greater than 3 months prior to study entry and that is assessed not to be related to tumor may be eligible).
• Patients with metastatic disease.
• History of uncontrolled or labile hypertension, defined as blood pressure greater than 150/100mmHg (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 grade greater than or equal to 2), systolic blood pressure greater than 180 mm Hg if diastolic blood pressure less than 90 mm Hg, or diastolic blood pressure greater than 90 mm Hg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment. Patients who have medication controlled hypertension are eligible for the study.
• Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris or uncontrolled angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant peripheral vascular disease (Grade II or greater).
• Psychiatric or neurologic illness that would limit compliance with study requirements.
• Patients with serious illness or medical condition.
• Active infection within 14 days before beginning treatment.
• Patients may not be receiving any other investigational agents.
• History of a malignancy in the last five years other than in situ carcinoma of the cervix, or non-melanomatous skin cancers.
• Patients must not be on therapeutic anticoagulation or chronic daily treatment with aspirin 325mg/day within 10 days prior to day 1 on study. Prophylactic anticoagulation during perioperative period is acceptable. Full dose aspirin post surgical resection is acceptable. Low dose aspirin 81mg/day and anticoagulation for line protection are allowed in the perioperative period and the adjuvant setting.
• Women who are breast feeding.
• History of stroke or transient ischemic attack within 6 months.
• History of pulmonary embolism, deep venous thrombosis or other thrombo-embolic event within 6 months prior to study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

University Hospital for Lung Diseases

Zagreb, Croatia

Location

Related Publications (3)

• Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, Brouchet L, Quoix E, Westeel V, Le Chevalier T. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol. 2000 Aug;18(16):2981-9. doi: 10.1200/JCO.2000.18.16.2981.

  PMID: 10944131 BACKGROUND

• Vansteenkiste J, Betticher D, Eberhardt W, De Leyn P. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small cell lung cancer. J Thorac Oncol. 2007 Aug;2(8):684-5. doi: 10.1097/JTO.0b013e31811f47ad. No abstract available.

  PMID: 17762333 BACKGROUND

• Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, Goldstraw P, Hatton M, Hopwood P, Manegold C, Schramel F, Smit H, van Meerbeeck J, Nankivell M, Parmar M, Pugh C, Stephens R. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet. 2007 Jun 9;369(9577):1929-37. doi: 10.1016/S0140-6736(07)60714-4.

  PMID: 17544497 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; Cisplatin; Bevacizumab; Surgical Procedures, Operative; Etoposide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

No primary or secondary goals were met because of low accrual for which the study was closed.

Results Point of Contact

• Title: Caryn Steakley, Deputy Clinical Director
• Organization: National Cancer Institute, National Institutes of Health

steaklec@nih.gov

240-858-3749

Study Officials

• Giuseppe Giaccone, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Clinical Director

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: November 30, 2018
• Results First Posted: August 21, 2012

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1); US (1)