Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Lung Cancer, Bevacizumab, Carboplatin, Docetaxel, Avastin, NSCLC, Anti-VEGF monoclonal antibody, rhuMAb-VEGF, Paraplatin®, Taxotere
Brief summary
The goal of this clinical research study is to evaluate the effectiveness of Avastin® in combination with docetaxel and carboplatin in the treatment of lung cancer. The safety of this combination will also be studied.
Detailed description
Avastin® is a humanized monoclonal antibody that binds to vascular endothelial growth factor (VEGF). VEGF plays an important role in the growth of both normal and abnormal blood vessels. Avastin® is designed to prevent or slow down the growth of cancer cells by blocking the effects of VEGF. Docetaxel and carboplatin are standard chemotherapy drugs that have been approved by the FDA for the treatment of NSCLC. Docetaxel and carboplatin are designed to work by stopping the division of cancer cells. If you are found to be eligible, you will begin receiving Avastin®, docetaxel, and carboplatin. Avastin®, carboplatin, and docetaxel will be given by vein once every 3 weeks. The first dose of Avastin® will be given over 90 minutes. The second dose of Avastin® will be given over 60 minutes. All other doses of Avastin® will be given over 30 minutes. Carboplatin and docetaxel will always be given over 30 minutes. They will be given on the same day every 3 weeks (1 cycle). You may receive up to 6 cycles of treatment. You will receive standard premedication with dexamethasone to help decrease the risk of side effects. Dexamethasone will be taken before you receive your docetaxel infusion. During the study, you will have blood tests (about 2 teaspoons) every 3 weeks to look at your blood counts. These samples will be used only for routine lab tests. You will be seen by a physician every 3 weeks and given a physical exam. Your blood pressure will be monitored, and you will be asked about any side effects you are experiencing. A performance status evaluation will also be done. In addition, you will have a urine test every 2 cycles of treatment. After 2 cycles of treatment (6 weeks), you will have a chest x-ray and computerized tomography (CT) or magnetic resonance imaging (MRI) scan to evaluate the status of the disease. These will be repeated every 2 cycles. Your continued participation in this study depends on how your cancer responds to the study drugs. Your doctor may decide to take you off this study if you experience significant side effects or your medical condition worsens. You may continue receiving bevacizumab for as long as your cancer responds to study treatment. You will be followed-up on by phone or at routine clinic visits for at least 12 months to monitor your condition and disease status. This is an investigational study. Avastin® has been approved by the FDA for the treatment of colorectal cancer. Docetaxel and carboplatin are FDA approved and commercially available. The use of these drugs together in this study is experimental. A total of 50 patients will take part in this study. All participants will be enrolled at M. D. Anderson.
Interventions
DRUGBevacizumab (Avastin)
15 mg/kg intravenously (IV) every 3 weeks
DRUGCarboplatin
AUC 6 IV every 3 weeks
DRUGDocetaxel
75 mg/m2 IV every 3 weeks
Sponsors
Genentech, Inc.
M.D. Anderson Cancer Center
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. Men and women, at least 18 years old, with histologically confirmed, advanced stage IIIB or IV NSCLC for whom no curative options exist and for whom docetaxel and carboplatin is a reasonable treatment option; 2. At least 1 target lesion that is unidimensionally measurable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and has not been previously irradiated; 3. Eastern Cooperative Oncology Group Performance Status of 0 or 1, (determined within 2 weeks prior to receiving study medication; 4. Ability to understand and adhere to the protocol requirements, and give informed consent 5. Use of effective means of contraception (men and women) in subjects of child-bearing potential. Child-bearing potential is defined as follows: A woman of childbearing potential is a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses at any time in the preceding 12 consecutive months).
Exclusion criteria
1. Patients who have had docetaxel in nonradiosensitizing therapy 2. Patients who have received prior full dose systemic chemotherapy for NSCLC (ie neoadjuvant, adjuvant, or metastatic) within the last 6 months. 3. Eastern Cooperative Oncology Group (ECOG) status of 2 or greater 4. Screening clinical laboratory values:\*absolute neutrophil count (ANC) of \<1,500/µL \*Platelet count of \<75,000/µL \* international normalized ratio (INR) \>/= 1.5 \*T bilirubin elevation above normal (MDACC upper normal limit is 1.0 mg/dL) \*Serum creatinine of \>2.0 mg/dL \*Hemoglobin of \<9 mg/dL (may be transfused or receive epoetin alfa \[e.g., Epogen®\] to maintain or exceed this level) \*The pt is ineligible if: 1.alk phos\>5xULN; 2.AST or ALT \>5xULN; 3.alk phos \>1xULN but \</= 2.5xULN AND AST or ALT \>1.5xULN but \</=5xULN;4.alk phos \>2.5xULN but \</=5xULN AND AST or ALT \> 1xULN but\</= 1.5xULN; 5.alk phos \>2.5xULN but\</=5xULN AND AST or ALT \>1.5xULN but \</=5xULN 5. Inability to comply with study and/or follow-up procedures 6. History of other disease, active infection, metabolic dysfunction , physical examination finding, or clinical laboratory finding which is uncontrolled requiring medical intervention giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications. 7. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a bevacizumab cancer study 8. Prior exposure to anti-VEGF therapy 9. Blood pressure of \> 140/90 mmHg as documented in two consecutive blood pressure readings within 4 hours 10. Any prior history of hypertensive crisis or hypertensive encephalopathy 11. New York Heart Association (NYHA) Grade II or greater congestive heart failure 12. History of myocardial infarction or unstable angina within 6 months 13. History of stroke or transient ischemic attack within 6 months 14. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) 15. Evidence of bleeding diathesis or coagulopathy 16. Presence of central nervous system or brain metastases at any time 17. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study 18. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 19. Pregnant (positive pregnancy test) or lactating 20. 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 \< 1g of protein in 24 hours to be eligible). 21. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 22. Serious, non-healing wound, ulcer, or bone fracture 23. Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, cavitation. 24. History of hemoptysis (bright red blood of 1/2 teaspoon or more) 25. Full dose anticoagulation, chronic use of Aspirin (\>325 mg/day) or NSAIDs 26. Inability to comply with study and/or follow-up procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression-Free Survival (PFS) | Baseline up to 12 months or disease progression/death | Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naı¨ve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standards, front-line, platinum-based doublets have not been extensively explored.We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naı¨ve patients with advanced, on squamous NSCLC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS)- 5 Years | Baseline start of treatment to death, assessed up to 6 years | Secondary endpoints of the study included the assessment of overall survival, disease control rate (CR þPR þ SD, defined by RECIST16), and evaluation of the safety profile of this triple-agent regimen. All patients who received at least 1 dose of the study drug were analyzed for efficacy and toxicity endpoints. |
| Disease Control Rate | Baseline start of treatment to death, assessed up to 6 years | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1 .0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)= CR+ PR. |
Countries
United States
Participant flow
Pre-assignment details
The trial was interrupted before the planned 50 patients were enrolled because of slow accrual after bevacizumab became commercially available in the United States for NSCLC treatment.
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin, Docetaxel, and Bevacizumab Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Six cycles of chemotherapy plus bevacizumab were planned. Patients who demonstrated stable disease (SD), partial response (PR), or complete response (CR) to treatment continued on single-agent bevacizumab 15 mg/kg every 21 days until disease progression or intolerable toxicity. Patients who discontinued chemotherapy before 6 cycles of treatment were also allowed to continue on single-agent bevacizumab in the absence of progressive disease (PD). | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Screen Failure | 3 |
Baseline characteristics
| Characteristic | Carboplatin, Docetaxel, and Bevacizumab |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 40 |
| other Total, other adverse events | 25 / 40 |
| serious Total, serious adverse events | 13 / 40 |
Outcome results
Primary
Time to Progression-Free Survival (PFS)
Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naı¨ve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standards, front-line, platinum-based doublets have not been extensively explored.We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naı¨ve patients with advanced, on squamous NSCLC.
Time frame: Baseline up to 12 months or disease progression/death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin, Docetaxel, and Bevacizumab | Time to Progression-Free Survival (PFS) | 7.9 months |
Secondary
Disease Control Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1 .0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)= CR+ PR.
Time frame: Baseline start of treatment to death, assessed up to 6 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Carboplatin, Docetaxel, and Bevacizumab | Disease Control Rate | 95 percentage of participants |
Secondary
Overall Survival (OS)- 5 Years
Secondary endpoints of the study included the assessment of overall survival, disease control rate (CR þPR þ SD, defined by RECIST16), and evaluation of the safety profile of this triple-agent regimen. All patients who received at least 1 dose of the study drug were analyzed for efficacy and toxicity endpoints.
Time frame: Baseline start of treatment to death, assessed up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Carboplatin, Docetaxel, and Bevacizumab | Overall Survival (OS)- 5 Years | 16.5 months |