Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Resected, Carboplatin, Docetaxel, Bevacizumab, Erlotinib
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.
Interventions
DRUGDocetaxel/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.
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.
Sponsors
Genentech, Inc.
Sanofi
SCRI Development Innovations, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | 1 year | The length of time, in months, that patients were alive from the end of their treatment without any signs or symptoms of their disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 2 years | Adverse Events occuring in \>15% of patients |
| 2-year Survival | 24 months | Proportion of patients known to still be alive 2 years after coming on study |
| Overall Survival (OS) | 18 months | The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib 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. | 55 |
| Docetaxel and Carboplatin 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. | 57 |
| Total | 112 |
Baseline characteristics
| Characteristic | Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Docetaxel and Carboplatin | Total |
|---|---|---|---|
| Age, Continuous | 64 years | 64 years | 64 years |
| Region of Enrollment United States | 55 participants | 57 participants | 112 participants |
| Sex: Female, Male Female | 26 Participants | 29 Participants | 55 Participants |
| Sex: Female, Male Male | 29 Participants | 28 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 55 | 55 / 57 |
| serious Total, serious adverse events | 14 / 55 | 14 / 57 |
Outcome results
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.
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Disease-free Survival | NA months |
| Docetaxel and Carboplatin | Disease-free Survival | 55.1 months |
Secondary
2-year Survival
Proportion of patients known to still be alive 2 years after coming on study
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | 2-year Survival | 78.2 percentage of participants |
| Docetaxel and Carboplatin | 2-year Survival | 71.9 percentage of participants |
Secondary
Overall Survival (OS)
The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Overall Survival (OS) | NA months |
| Docetaxel and Carboplatin | Overall Survival (OS) | NA months |
Secondary
Safety
Adverse Events occuring in \>15% of patients
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Pain | 23 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Fatigue | 37 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Nausea | 32 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Diarrhea | 26 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Anemia | 18 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Neutrophil count decreased | 20 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | White blood cell decreased | 18 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Alopecia | 21 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Platelet count decreased | 13 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Constipation | 14 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Dyspnea | 14 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Anorexia | 12 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Hyperglycemia | 18 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Dysgeusia | 12 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Mucositis | 12 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Vomiting | 10 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Cough | 12 participants |
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | Safety | Peripheral sensory neuropathy | 15 participants |
| Docetaxel and Carboplatin | Safety | Dysgeusia | 14 participants |
| Docetaxel and Carboplatin | Safety | Pain | 15 participants |
| Docetaxel and Carboplatin | Safety | Constipation | 18 participants |
| Docetaxel and Carboplatin | Safety | Fatigue | 41 participants |
| Docetaxel and Carboplatin | Safety | Peripheral sensory neuropathy | 2 participants |
| Docetaxel and Carboplatin | Safety | Nausea | 36 participants |
| Docetaxel and Carboplatin | Safety | Dyspnea | 17 participants |
| Docetaxel and Carboplatin | Safety | Diarrhea | 24 participants |
| Docetaxel and Carboplatin | Safety | Mucositis | 12 participants |
| Docetaxel and Carboplatin | Safety | Anemia | 28 participants |
| Docetaxel and Carboplatin | Safety | Anorexia | 18 participants |
| Docetaxel and Carboplatin | Safety | Neutrophil count decreased | 26 participants |
| Docetaxel and Carboplatin | Safety | Cough | 8 participants |
| Docetaxel and Carboplatin | Safety | White blood cell decreased | 27 participants |
| Docetaxel and Carboplatin | Safety | Hyperglycemia | 11 participants |
| Docetaxel and Carboplatin | Safety | Alopecia | 21 participants |
| Docetaxel and Carboplatin | Safety | Vomiting | 13 participants |
| Docetaxel and Carboplatin | Safety | Platelet count decreased | 20 participants |