Lower Dose Chemotherapy Given More Frequent With Avastin to Treat Advanced Non-Squamous Non-Small Cell Lung Cancer

NCT00655850 | Completed Phase 2 Results DMC

• 2 other identifiers: F070727010UAB 0709
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to determine the overall progression-free survival (PFS) in patients with advanced or metastatic (Stage IIIB - pleural effusion/IV), non-squamous histology NSCLC treated with metronomic chemotherapy plus Avastin. Also, currently there are no defined markers that predict for clinical benefit to Avastin. Preliminary studies show that there are several observations that support the concept of metronomic chemotherapy with or without the combination of an anti-angiogenic agent. The metronomic chemotherapy with Avastin was shown to enhance the clinical endpoints of the study (response rate and progressive-free survival). Proof of metronomic scheduling requires the development of appropriate intermediate surrogate markers. Several markers will be assessed.

Conditions

Non-Small Cell Lung Cancer

Keywords

Lung Cancer; Non-Small Cell Lung Cancer; Metronomic Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression Free Survival is defined as the number of days from the day the subject started treatment to the day the subject experiences disease progression in accordance with the Response Evaluation Criteria Solid Tumors (RECIST v1.0). The RECIST criteria indicates progression as a 20% increase in the total tumor measurement over nadir value or the appearance of new lesions.

  Baseline to 24 months

Secondary Outcomes (3)

• Number of Participants With Adverse Events

  Baseline through duration of treatment an average of 1 year

• Overall Survival (OS)

  Baseline up to 84 months

• Objective Response Rate

  Baseline up to 12 months

Study Arms (1)

Paclitaxel and Gemcitabine + Avastin

EXPERIMENTAL

Patients will be treated with metronomic chemotherapy with paclitaxel and gemcitabine weekly for 3 out of 4 weeks which constitutes one cycle (4 weeks). Avastin will be administered every 2 weeks. Treatment with metronomic chemotherapy and Avastin will continue for a total of 6 cycles unless there is evidence of disease progression, intolerable toxicity, or withdrawal of consent. Maintenance therapy with Avastin will continue until disease progression, intolerable toxicity, or withdrawal of consent.

Drug: Paclitaxel; Drug: Gemcitabine; Biological: Avastin

Interventions

Paclitaxel DRUG

* Prior to receiving paclitaxel, all patients will receive the following premedications one hour before the infusion: * Dexamethasone 20mg, intravenously (IV) * Diphenhydramine 50 mg IV * Ranitidine 50 mg IV * Paclitaxel will be administered after the gemcitabine infusion as a 1 hour (IV) infusion. * The initial dose of paclitaxel is 80 mg/m2/weekly for 3 out of 4 weeks (Day 1, 8, 15) Paclitaxel Dose Levels: * Dose Level 1 \_\_\_\_\_\_\_\_80 mg/m2/weekly * Dose Level -1 \_\_\_\_\_\_\_\_70 mg/m2/weekly

Also known as: Taxol

Paclitaxel and Gemcitabine + Avastin

Gemcitabine DRUG

Premedication * Prophylactic antiemetics: 5-HT3-receptor antagonist prior to infusion with gemcitabine. * Prior to receiving paclitaxel chemotherapy * Gemcitabine will be given at the initial dose of 200mg/m2/week (Dose Level 1) for 3 out of 4 weeks (Day 1, 8, 15), as a 30 minute (IV) infusion. * The dose of gemcitabine can be escalated to 300mg/m2/weekly (Dose Level 2) after the first cycle of treatment if no significant toxicity is experienced. Gemcitabine Dose Levels: * Dose Level 2 \_\_\_\_\_\_\_\_300 mg/m2/weekly * Dose Level 1 \_\_\_\_\_\_\_\_200 mg/m2/weekly * Dose Level -1 \_\_\_\_\_\_\_\_150 mg/m2/weekly

Also known as: Gemzar

Paclitaxel and Gemcitabine + Avastin

Avastin BIOLOGICAL

* The dose of Avastin is 10 mg/kg IV every 2 weeks * It will be administered following the administration of chemotherapy * The first infusion will be administered over 90 minutes; if well tolerated, the second and subsequent doses will be administered as a 60-minute and 30-minute infusion, respectively. * It should not be administered or mixed with dextrose solutions.

Also known as: Anti-VEGF

Paclitaxel and Gemcitabine + Avastin

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Inability to comply with study and/or follow-up procedures
• Life expectancy of less than 12 weeks
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
• Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to Day 1
• History of stroke or transient ischemic attack within 6 months prior to Day 1
• Known CNS disease, except for treated brain metastasis Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294 - 0104, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Paclitaxel; Gemcitabine; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Francisco Robert, MD
• Organization: University of Alabama at Birmingham

pacorobertuab@cs.com

205-934-5077

Study Officials

• Francisco Robert, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 4, 2008
• First Posted: April 10, 2008
• Study Start: March 1, 2008
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2016
• Last Updated: July 17, 2017
• Results First Posted: May 24, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)