Clinical trial NCT00960297: Preoperative Chemotherapy and Bevacizumab in Patients With Stage IB (>4 cm), II, or Select Stage III NSCLC
Official title: Phase II Trial of Preoperative Chemotherapy and Bevacizumab in Patients With Stage IB (>4 cm), II, or Select Stage III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
NSCLC
Preoperative chemotherapy
Bevacizumab
Avastin
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2009-08-17
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 36 months
Secondary outcomes:
measure: Clinical & Pathologic Response Rate
timeFrame: 60 months
measure: Complete Resection Rate
timeFrame: 60 months
measure: Number of Participants Experiencing Adverse Events as a Measure of Toxicity
timeFrame: 45 months
measure: Progression-free Survival
timeFrame: 60 months
measure: Overall Survival
timeFrame: 60 months
Other outcomes:
Locations:
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Grand Rapids
country: United States
facility: Grand Rapids Clinical Oncology Program
state: Michigan
city: Portsmouth
country: United States
facility: Portsmouth Regional Hospital
state: New Hampshire
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David R Spigel, M.D.
role: STUDY_CHAIR
References: