Carboplatin, Docetaxel, Bevacizumab, and Erlotinib Versus Chemotherapy Alone in Resected NSCLC

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00621049
• Other study ID #: SCRI LUN 142
• Secondary ID: US_IST_12218AVF3
• Status: Completed
• Phase: Phase 2
• First received: December 26, 2007
• Last updated: May 13, 2015
• Start date: December 2007
• Est. completion date: February 2014

Study information

• Verified date: May 2015
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: February 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Docetaxel/Carboplatin/Bevacizumab/Erlotinib
Docetaxel 75mg/m2 IV D1 Carboplatin AUC=6 IV D1 Bevacizumab 15mg/kg IV D1 Docetaxel should be administered before carboplatin. After completion of four cycles of treatment, patients in Cohort A will then proceed with Maintenance treatment defined as follows: Maintenance Treatment for patients in Cohort A: Bevacizumab 15mg/kg IV D1 Erlotinib 150mg PO daily Treatment cycle = 21 days. Patients will complete 8 cycles (24 weeks) of maintenance therapy unless there is evidence of disease recurrence or unacceptable toxicity.
• Docetaxel/Carboplatin
Adjuvant Treatment Cohort B: Docetaxel 75mg/m2 IV D1 Carboplatin AUC=6 IV D1 Docetaxel should be administered before carboplatin. Treatment cycle = 21 days. Patients in Cohort B will complete 4 cycles of treatment.

Locations

Country	Name	City	State
United States	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico
United States	Hematology Oncology Life Center	Alexandria	Louisiana
United States	Northeast Alabama Medical Center	Anniston	Alabama
United States	Cancer Care of Western North Carolina	Asheville	North Carolina
United States	Medical Oncology Associates of Augusta	Augusta	Georgia
United States	Hematology Oncology Clinic, LLP	Baton Rouge	Louisiana
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Associates in Hematology Oncology	Chattanooga	Tennessee
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	St. Louis Cancer Care	Chesterfield	Missouri
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	Northeast Arkansas Clinic	Jonesboro	Arkansas
United States	Baptist Hospital East	Louisville	Kentucky
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Wellstar Cancer Research	Marietta	Georgia
United States	Hematology Oncology Associates of Northern NJ	Morristown	New Jersey
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Peninsula Cancer Institute	Newport News	Virginia
United States	Nebraska Methodist Cancer Center	Omaha	Nebraska
United States	Portsmouth Regional Hospital	Portsmouth	New Hampshire
United States	Gulfcoast Oncology Associates	St. Petersburg	Florida
United States	Providence Medical Group	Terre Haute	Indiana
United States	RHHP/Hope Cancer Center	Terre Haute	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Genentech, Inc., Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival	The length of time, in months, that patients were alive from the end of their treatment without any signs or symptoms of their disease.	1 year	No
Secondary	Safety	Adverse Events occuring in >15% of patients	2 years	Yes
Secondary	2-year Survival	Proportion of patients known to still be alive 2 years after coming on study	24 months	No
Secondary	Overall Survival (OS)	The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death	18 months	No