Clinical trial NCT00621049: Carboplatin, Docetaxel, Bevacizumab, and Erlotinib Versus Chemotherapy Alone in Resected NSCLC
Official title: Randomized Phase II Trial of Adjuvant Carboplatin, Docetaxel, Bevacizumab, and Erlotinib Versus Chemotherapy Alone in Patients With Resected Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Resected
Carboplatin
Docetaxel
Bevacizumab
Erlotinib
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Sanofi
First posted: 2008-02-22
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicenter randomized phase II trial to examine the safety and efficacy of carboplatin, docetaxel, bevacizumab followed by maintenance bevacizumab and erlotinib in patients with completely resected stage IB, II, and select III NSCLC.


Eligibility criteria: Inclusion Criteria:

1. Patients must have histologically-confirmed non-small cell lung cancer (adenocarcinoma, squamous, large cell and undifferentiated). Mixed small cell and non-small histologies are excluded.
2. Patients with completely resected (R0) stage IB, II, and select III NSCLC. The following stages are eligible:

   IB T2 N0 IIA T1 N1 IIB T2 N1 IIB T3 N0 IIIA T3 N1
   * Bronchioalveolar carcinoma that presents as a single, solitary discrete nodule or mass may be included
   * Patients determined to have N2 disease, that was not apparent radiologically preoperatively (and completely resected) can be included.
3. Complete surgical resection defined as the appropriate pulmonary parenchymal resection including lobectomy, bilobectomy, sleeve lobectomy, and pneumonectomy with histologically confirmed negative bronchial margins. Patients treated by segmentectomy or wedge resection are not eligible for this study. Additionally all patients must have had either a mediastinal node dissection or at least, sampling of 2 mediastinal nodal stations (levels 4,7,and 9 for right-sided tumors, and levels 5,6,7, and 9 for left-sided tumors are suggested.)
4. No evidence of metastatic disease
5. ANC \>= 1500, platelets \>= 100,000 and hemoglobin \>= 10.0.
6. Total bilirubin \<= ULN. AST and ALT and alkaline phosphatase must be WNL
7. Serum creatinine \<= 1.5mg/dl (If greater than 1.5, the creatinine clearance, calculated according to the Cockroft-Gault formula, must be \>= 50ml/min).
8. Patients may have had no previous chemotherapy, radiation therapy, angiogenesis inhibitor, or tyrosine kinase inhibitor for non-small cell lung cancer.
9. Patients must be able to understand the nature of this study and give written informed consent.
10. Age \>= 18 years
11. Ability to start treatment between 8 and 12 weeks following surgery.
12. Ability to take oral medication.

Exclusion Criteria:

1. Patients with preoperative radiologic evidence of N2 disease by either PET or CT scan (i.e. radiological evidence of metastasis to ipsilateral mediastinal and subcarinal nodes) that is confirmed as N2 disease histologically are excluded. - PLEASE SEE EXCEPTION in section 3.1.2 of protocol
2. Mixed small cell and non-small cell histologies
3. Pulmonary carcinoid tumors
4. Positive bronchial margins
5. History of prior malignancy within 5 years with the exception of skin cancer or cervical carcinoma in situ.
6. Women who are pregnant (positive pregnancy test) or breast-feeding. Subjects of childbearing potential or with partners of childbearing potential (women and men) must use effective birth control measures during treatment.
7. Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment.
8. Patients with seizures not controlled with standard medical therapy.
9. Patients with active infection requiring parenteral antibiotics
10. Patients who have had major surgical procedure, open biopsy, or significant traumatic injury within 8 weeks of beginning study treatment or anticipation of need for major surgical procedure during the course of the study
11. Fine needle aspiration, core biopsy or other minor surgical procedure (excluding placement of a vascular access device) within 7 days of beginning study treatment.
12. Patients receiving thrombolytic therapy within 10 days of starting study treatment are also ineligible. Patients may receive prophylactic anticoagulation therapy, 1 mg coumadin daily for port clot prophylaxis.
13. Patients with proteinuria at screening as demonstrated by either:

    * Urine protein creatinine (UPC) ratio \>= 1.0 at screening OR
    * Urine dipstick for proteinuria \>= 2+ (patients discovered to have \>= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate \>= 1 g of protein in 24hours to be eligible).
14. Patients with serious nonhealing wound, ulcer, or bone fracture.
15. Patients with evidence of bleeding diathesis or coagulopathy.
16. Patients with history of hemoptysis defined as bright red blood of ½ teaspoon or more per episode) within 8 weeks prior to study treatment.
17. History of myocardial infarction or unstable angina within 6 months of beginning study treatment.
18. Inadequately controlled hypertension (defined as systolic blood pressure \> 150 and /or diastolic blood pressure \> 100 mmHg on antihypertensive medications).
19. New York Heart Association (NYHA) grade II or greater CHF.
20. Serious cardiac arrhythmia requiring medication.
21. Symptomatic peripheral vascular disease.
22. History of stroke or transient ischemic attack within 6 months prior to beginning bevacizumab.
23. Any prior history of hypertensive crisis or hypertensive encephalopathy.
24. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning study treatment.
25. ECOG Performance status \> 1.
26. Peripheral neuropathy\> grade 1.
27. Known hypersensitivity to any component of study drugs including platinum or to drugs formulated with polysorbate 80.
28. Impaired oral absorption.
29. Inability to comply with study and/or follow-up procedures.

Primary outcomes:
measure: Disease-free Survival
timeFrame: 1 year
Secondary outcomes:
measure: Safety
timeFrame: 2 years
measure: 2-year Survival
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 18 months
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Medical Center
state: Alabama
city: Jonesboro
country: United States
facility: Northeast Arkansas Clinic
state: Arkansas
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: St. Petersburg
country: United States
facility: Gulfcoast Oncology Associates
state: Florida
city: Augusta
country: United States
facility: Medical Oncology Associates of Augusta
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Cancer Research
state: Georgia
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Terre Haute
country: United States
facility: RHHP/Hope Cancer Center
state: Indiana
city: Louisville
country: United States
facility: Baptist Hospital East
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Alexandria
country: United States
facility: Hematology Oncology Life Center
state: Louisiana
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic, LLP
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Jackson
country: United States
facility: Jackson Oncology Associates
state: Mississippi
city: Chesterfield
country: United States
facility: St. Louis Cancer Care
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Cancer Center
state: Nebraska
city: Portsmouth
country: United States
facility: Portsmouth Regional Hospital
state: New Hampshire
city: Morristown
country: United States
facility: Hematology Oncology Associates of Northern NJ
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants
state: New Mexico
city: Asheville
country: United States
facility: Cancer Care of Western North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Chattanooga
country: United States
facility: Associates in Hematology Oncology
state: Tennessee
city: Chattanooga
country: United States
facility: Chattanooga Oncology Hematology Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David Spigel, M.D.
role: STUDY_CHAIR
References: