Phase I Dose-Escalating, Open-Label, Non-Placebo Controlled Study of BAY 43-9006 (Sorafenib) in Combination With Carboplatin, Paclitaxel and Bevacizumab in Previously Untreated Patients With Stage IIIB (With Malignant Pleural Effusions) or Stage IV Non-Small Cell Lung Cancer (NSCLC)
Phase I Dose-Escalating, Open-Label, Non-Placebo Controlled Study of BAY 43-9006 (Sorafenib) in Combination With Carboplatin, Paclitaxel and Bevacizumab in Previously Untreated Patients With Stage IIIB (With Malignant Pleural Effusions) or Stage IV Non-Small Cell Lung Cancer (NSCLC)
The goal of this study is to find the highest tolerable dose of BAY 43-9006 (sorafenib) and bevacizumab that can be given with paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC). The safety and effectiveness of this drug combination will also be studied.
Sorafenib is designed to stop the growth of cells that are caused by genetic changes often associated with cancer. Paclitaxel is designed to work by blocking the mechanisms of cell division in cancer cells, which may cause them to die. Carboplatin is designed to work by interfering with the growth of cancer cells by stopping cell division. Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the effects of a blood-vessel stimulating agent that plays an important role in the growth of both normal and abnormal blood vessels.
If you are found to be eligible to take part in this study, you will receive 4 different drugs during the study. This study will follow a 3-week schedule known as a study "cycle."
In the first part of the study, researchers are trying to find out the highest dose of the study drugs that can be safely given together. The first group of 6 participants will receive lower doses of sorafenib and bevacizumab. The doses of paclitaxel and carboplatin will stay the same for up to 6 cycles for the study for all participants who complete 6 cycles. If the first 6 participants do not have intolerable side effects, the next group of patients will get higher doses of bevacizumab. The doses of sorafenib will be increased until at least some participants have unacceptable side effects. The dose that you get will not increase during the study, but if you have bad side effects, your dose of sorafenib, bevacizumab, paclitaxel, or carboplatin may be lowered at future visits.
On Day 1 of each cycle, you will be given bevacizumab, paclitaxel, and carboplatin in your vein as an infusion. Paclitaxel will be infused over 3 hours, followed by carboplatin over 30 minutes, followed by bevacizumab over 90 minutes for the first 2 cycles. Your bevacizumab infusion may be given over a shorter time period in later cycles. You will stay in the clinic for at least 30 minutes after your bevacizumab infusion for all cycles after 1 and 2. You will take sorafenib by mouth twice a day, once in the morning before 11:00 am and once in the evening before 11:00 p.m. Sorafenib should be taken with about 1 cup of water on an empty stomach (either 1 hour before a meal or 2 hours after a meal) or with a moderate fat diet (about 30% of calories from fat). Sorafenib must be swallowed whole without chewing.
On Day 1 of Cycles 1 and 2, your complete medical history will be recorded, and you will have a physical exam including measurement of your vital signs and weight. You will be asked questions to find out how the disease is progressing and how the disease affects the quality of life. You will be asked about any side effects you may be experiencing. If possible, you should not change your medications between Cycle 1 Day 1 until all procedures are completed on Cycle 2 Day 3. Blood (about 5 teaspoons) and urine will be collected for routine tests. You will receive infusions of paclitaxel, carboplatin, and bevacizumab into a vein.
On Cycle 1 Day 2, blood (about 1 tablespoon) will be drawn for routine tests.
On Cycle 1 Day 3, blood (about 1 tablespoon) will be collected for routine tests. After your blood samples have been collected, you will be given your morning dose of sorafenib. You will be given sorafenib to take at home that night.
On Cycle 2 Day 2, blood (about 1 tablespoon) will be drawn for routine tests. Once your blood samples has been collected, your morning dose of sorafenib will be given to you in the clinic. You will be given sorafenib to take at home that night.
On Cycle 2 Day 3, blood (about 1 tablespoon) will be drawn for routine tests. Once your blood sample has been collected, your morning dose of sorafenib will be given to you in the clinic. Before you leave the clinic, you will be given enough sorafenib tablets to last until your next cycle visit.
On Cycles 1-2 Days 8 and 15, your complete medical history will be recorded, and you will have a physical exam including measurement of your vital signs and weight. You will have a performance status evaluation. You will be asked about any side effects you may be experiencing. Blood (about 5 teaspoons) and urine will be collected for routine tests.
On Day 1 of Cycle 3 and remaining cycles, you will return all study medication and/or the empty bottle. Your complete medical history will be recorded, and you will have a physical exam including measurement of your vital signs and weight. You will be asked questions to determine how the disease is progressing, and how the disease affects your quality of life. You will be asked about any side effects you may be experiencing. Blood (about 5 teaspoons) and urine will be collected for routine tests. You will receive infusions of paclitaxel, carboplatin, and bevacizumab. You will stay in the clinic for at least 30 minutes after your bevacizumab infusion. Before you leave the clinic, you will be given enough sorafenib to last until the next cycle.
On Days 8 and 15 of Cycle 3 and remaining cycles, blood (about 5 teaspoons) and urine will be collected for routine tests.
On Day 1 of all odd-numbered cycles (starting with Cycle 3, 5, 7, 9...), you will have CT scans, MRI scans, and/or other x-rays to check the status of the disease.
Modified Dose Levels 4 and 5:
To find out if interrupted dosing of sorafenib will result in fewer or less severe side effects, 2 additional dose levels, where the dose of sorafenib will be changed (modified), will be performed. For Modified Dose Level 4, sorafenib will be interrupted for 2 days after every 4-5 days . For Modified Dose Level 5, sorafenib will be interrupted for 1 week after 2 weeks of continuous therapy.
For these 2 additional dose levels, the sorafenib dosing schedule will be changed. There will be 6 patients enrolled at each dose level. Participants in Dose Level 4 may continue treatment for 4 to 6 cycles. This is done to accurately evaluate the dose level. Researchers will evaluate any side effects related to this new dosing schedule of sorafenib. After all 6 patients have been enrolled in Dose level 4, then 6 additional patients will be enrolled in Dose Level 5. If no intolerable side effects are seen at Dose Level 5, then 6 additional patients can be enrolled in that dose level. This is done so additional PK testing can be done.
For Modified Dose Level 4 and 5, "on Day 1 of Cycle 1 and 2, you will be given bevacizumab, paclitaxel, and carboplatin in your vein as an infusion. Paclitaxel will be infused over 3 hours, followed by carboplatin over 30 minutes, followed by bevacizumab over 90 minutes for the first 2 cycles. Your bevacizumab infusion may be given over a shorter time period in later cycles. You will stay in the clinic for at least 30 minutes after your bevacizumab infusion for all cycles after 1 and 2. "
Modified Dose level 4:
For Modified Dose level 4, on Day 3 through Day 19 of Cycle 1, you will receive sorafenib by mouth in the morning, after the morning PK tests have been collected (on Day 3 only). Participants will take the evening dose of sorafenib on their own. After that, participants will take sorafenib on their own twice a day for 5 days on and 2 days off. This will continue through Day 19 on an outpatient basis.
On Day 2 through Day 19 of Cycle 2, you will receive sorafenib by mouth in the morning, after the morning PK tests have been collected on Day 2 (Cycle 2 only). Participants will take the evening dose of sorafenib on their own. After that, participants will take sorafenib on their own twice a day for 5 days on and 2 days off. This will continue through Day 19 on an outpatient basis. The modified dose level 4 and 5 patients will not take sorafenib on Days 1, 2, 6, 7, 13, 14, 20 and 21 of Cycle 1.
Modified Dose level 5:
For Modified Dose Level 5, on Day 3 through Day 15 of Cycle 1, you will receive sorafenib by mouth in the morning, after the morning PK tests have been collected (on Day 3 only). Participants will take the evening dose of sorafenib on their own. After that, participants will take sorafenib on their own twice a day for 14 days through Day 15 on an outpatient basis. Participants will not take sorafenib on Days 1, 2 and Days 16-21.
On Day 2 through Day 15 of Cycle 2, you will receive sorafenib by mouth in the morning, after the morning PK tests have been collected (on Day 2 Cycle 2 only). Participants will take the evening dose of sorafenib on their own. After that, participants will take sorafenib on their own twice a day for 14 days through Day 15 on an outpatient basis.Participants will not take sorafenib on Days 1, 2 and Days 16-21.
You may stay on study as long as the disease does not get worse, and intolerable side effects do not develop.
Once you are off study, you will have an end-of-study visit 21-35 days after your last dose of the study drug. You will need to return all unused study medication and/or the empty bottles. You will have a physical exam, including measurement of your vital signs, height, and weight. You will have a performance status evaluation and an ECG. You will be asked about any side effects you may be experiencing. CT scans, MRIs, and/or x-rays will be taken to check the status of the disease. Blood (about 5 teaspoons) and urine will be collected for routine blood tests. Women who are able to have children must have a negative blood (about 1-2 teaspoons ) pregnancy test.
This is an investigational study. Sorafenib, paclitaxel, carboplatin, and bevacizumab are all FDA approved and commercially available. The combination of these 4 drugs is not FDA approved, and it has been authorized for use in research only. Up to 60 patients will take part in this multicenter study. Up to 30 patients will be enrolled at M.D. Anderson.
Inclusion Criteria:
Exclusion Criteria: