Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, NSCLC, Preoperative chemotherapy, Bevacizumab, Avastin
Brief summary
The rationale for this multicenter, phase II trial is to examine the impact of carboplatin/paclitaxel with bevacizumab in the preoperative treatment of patients with stage IB (\> 4.0 cm), II, and select stage III NSCLC. If this novel regimen proves to be safe and active in this setting, this would provide rationale for further investigation in a larger, prospective, randomized setting.
Detailed description
Adjuvant chemotherapy for patients with completely resected stage II and select stage III NSCLC is considered standard therapy. At least three large, prospective randomized trials have proven the benefit of adjuvant chemotherapy in improving survival in these patients (with a magnitude of benefit ranging from 4-12%). However, in patients who are not considered to be candidates for up-front complete resection, preoperative therapy may be indicated. Many of these patients will subsequently be eligible for resection (bimodality therapy). The rationale for this multicenter, Phase II trial is to examine the impact of carboplatin/paclitaxel with bevacizumab in the preoperative treatment of patients with stage IB (\>4.0 cm), II, and select stage III NSCLC. This trial will be conducted by the Sarah Cannon Research Institute Oncology Research Consortium. If this novel regimen proves to be safe and active in this setting, this would provide rationale for further investigation in a larger, prospective, randomized setting.
Interventions
DRUGCarboplatin
Carboplatin: AUC=6, given IV on Days 1, 22, 43, and 64
DRUGPaclitaxel
Paclitaxel: 200 mg/m2, given IV on Days 1, 22, 43, and 64
DRUGBevacizumab
Bevacizumab: 15 mg/kg, given IV on Days 1, 22, and 43 (Note: bevacizumab will not be dosed on Day 64 prior to surgery)
Sponsors
Genentech, Inc.
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>=18 years. 2. Histologically-confirmed NSCLC (adenocarcinoma, large cell, and undifferentiated). Patients with squamous histology are not eligible. 3. Life expectancy of at least 12 weeks. 4. Patients with the following stages of NSCLC: * T2 N0 tumors: Limited to tumors \>=4 cm. * T1-2 N1 tumors. * T3 N0-1 tumors (excluding superior sulcus tumors): Including tumors involving the chest wall, proximal airway, or mediastinal pleura where preoperative RT is not planned. * T1-2 N2 tumors: For patients with N2 disease involving 1 zone (Upper zone (R), AP zone (L), subcarinal zone, or lower zone) and nodes \<=2 cm in diameter. * T4 N0-1 tumors (excluding superior sulcus tumors): T4 lesions, other than malignant effusions where radiotherapy is not planned. 5. Patients with clinical N2 involvement must have histologic confirmation by mediastinoscopy (or alternate biopsy procedure). 6. Tumors should be considered potentially resectable. 7. No evidence of extrathoracic metastatic disease. 8. Patients must have measurable disease by RECIST version 1.1 criteria. 9. Patients must be candidates (medically) for chemotherapy followed by surgical resection. 10. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (with the exception of portacath or other central access catheter placement); at least 4 weeks must have elapsed from the time of a major surgery. 11. Laboratory values as follows: * Absolute neutrophil count (ANC) \>=1500/µL * Hemoglobin (Hgb) \>=9 g/dL * Platelets \>=100,000/uL * AST/SGOT and ALT/SGPT within normal limits (WNL) * Total bilirubin within normal limits (WNL) * Creatinine \<=1.5 mg/dL 12. ECOG Performance Status grade 0 or 1. 13. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. 14. Patient must be accessible for treatment and follow-up. 15. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
Exclusion criteria
1. Mixed small-cell and non-small cell histologies. 2. Pulmonary carcinoid tumors. 3. History of prior malignancy within 3 years, with the exception of non-melanoma skin cancer or carcinoma in situ. 4. Peripheral neuropathy \>= grade 1. 5. Patients receiving thrombolytic therapy within 10 days of starting study treatment are ineligible. Therapeutic anticoagulation is allowed if the anticoagulant dosing is stable. 6. History of acute myocardial infarction or unstable angina within 6 months prior to Day 1 of study treatment. 7. History of or stroke or ischemic attack within 6 months prior to Day 1 of study treatment. 8. Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg) in spite of medical management. 9. New York Heart Association (NYHA) class II or greater congestive heart failure (CHF). 10. Patients with significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of study treatment. 11. Any prior history of hypertensive crisis or hypertensive encephalopathy. 12. Patients with hematemesis or hemoptysis (\>=1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 of study treatment. 13. Proteinuria at screening, as demonstrated by either: * Urine protein: creatinine (UPC) ratio \>=1.0 (see Appendix A) at screening, or * Urine dipstick for proteinuria \>=2+ (patients discovered to have \>=2+ proteinuria on dipstick analysis should undergo a 24-hour urine collection and must have \<=1g of protein in 24 hours to be eligible). 14. Patients with a serious non-healing wound, active ulcer, or untreated bone fracture. 15. Patients with evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation). 16. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 of study treatment. 17. Women who are pregnant (positive pregnancy test) or lactating. 18. Use of any non-approved or investigational agent within 28 days of administration of the first dose of study drug. 19. Patients may not receive any other investigational or anti-cancer treatments while participating in this study. 20. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. 21. History of hypersensitivity to active or inactive excipients of any component of treatment. 22. Inability to comply with study and/or follow-up procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To Assess 3-year Overall Survival in Patients With Stage IB (>4.0 cm), II, or Select Stage III NSCLC Treated With Preoperative Carboplatin, Paclitaxel, and Bevacizumab Followed by Surgical Resection. | 36 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical & Pathologic Response Rate | 60 months | — |
| Complete Resection Rate | 60 months | — |
| Number of Participants Experiencing Adverse Events as a Measure of Toxicity | 45 months | An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a preexisting medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events are reported here. |
| Progression-free Survival | 60 months | — |
| Overall Survival | 60 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin/Paclitaxel/Bevacizumab Preoperative chemotherapy and bevacizumab
Bevacizumab : Bevacizumab: 15 mg/kg, given IV on Days 1, 22, and 43 (Note: bevacizumab will not be dosed on Day 64 prior to surgery)
Paclitaxel : Paclitaxel: 200 mg/m2, given IV on Days 1, 22, 43, and 64
Carboplatin : Carboplatin: AUC=6, given IV on Days 1, 22, 43, and 64 | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Venous port infection | 1 |
Baseline characteristics
| Characteristic | Carboplatin/Paclitaxel/Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
To Assess 3-year Overall Survival in Patients With Stage IB (>4.0 cm), II, or Select Stage III NSCLC Treated With Preoperative Carboplatin, Paclitaxel, and Bevacizumab Followed by Surgical Resection.
Time frame: 36 months
Population: Study ended early due to slow accrual.
Secondary
Clinical & Pathologic Response Rate
Time frame: 60 months
Population: Results were not analyzed as the study ended early due to slow accrual and incomplete data collection
Secondary
Complete Resection Rate
Time frame: 60 months
Population: Results were not analyzed as the study ended early due to slow accrual and incomplete data collection.
Secondary
Number of Participants Experiencing Adverse Events as a Measure of Toxicity
An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a preexisting medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events are reported here.
Time frame: 45 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin/Paclitaxel/Bevacizumab | Number of Participants Experiencing Adverse Events as a Measure of Toxicity | 4 Participants |
Secondary
Overall Survival
Time frame: 60 months
Population: Results were not analyzed as the study ended early due to slow accrual and incomplete data collection.
Secondary
Progression-free Survival
Time frame: 60 months
Population: Results were not analyzed as the study ended early due to slow accrual and incomplete data collection.