Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Patients With Carcinomas of Mullerian Origin
|First Received Date ICMJE||March 31, 2008|
|Last Updated Date||August 24, 2016|
|Start Date ICMJE||February 2008|
|Estimated Primary Completion Date||February 2018 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Number of Patients Who Complete Entire Treatment Course [ Time Frame: Total treatment course = 6 cycles (1 cycle is 21 days) ] [ Designated as safety issue: Yes ]
Rate of completers estimated along with a 95% confidence interval to evaluate the tolerability of this regimen.
|Original Primary Outcome Measures ICMJE
||The goal of this clinical research study is to learn about the safety and tolerability of paclitaxel and carboplatin when given in combination with Avastin to patients with ovarian, primary peritoneal, or fallopian tube cancer. [ Time Frame: 4 Years ] [ Designated as safety issue: Yes ]|
|Change History||Complete list of historical versions of study NCT00652119 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Systemic Exposure to Paclitaxel and Carboplatin [ Time Frame: Second and fourth 21 day cycle ] [ Designated as safety issue: No ]
Primary objective of pharmacokinetic studies is to determine whether rate and extent absorption of paclitaxel and carboplatin into systemic circulation when given by the intraperitoneal port (IP) route is influenced by concurrent administration of Avastin by vein. Sampling to define plasma concentration time courses of paclitaxel and carboplatin performed during second cycle without Avastin and fourth cycle of therapy with Avastin. Pharmacokinetic parameters and variables calculated according to standard equations. Concentration-time profiles of carboplatin and its metabolites analyzed by noncompartmental methods and/or nonlinear least squares regression. Mean values of pharmacokinetic parameters statistically compared using the two-tailed t-test.
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Patients With Carcinomas of Mullerian Origin|
|Official Title ICMJE||Pilot Trial of Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Treatment of Women With Newly Diagnosed, Optimally Cytoreduced Carcinoma of Mullerian Origin|
The goal of this clinical research study is to learn about the safety and tolerability of paclitaxel and carboplatin when given in combination with Avastin to patients with ovarian, primary peritoneal, or fallopian tube cancer.
Primary study goals:
To investigate the safety and tolerability of carboplatin and paclitaxel administered IP in combination with IV Avastin To determine if Avastin influences the pharmacokinetics of IP administered chemotherapeutic agents
Secondary study goals:
To determine the systemic exposure to paclitaxel and carboplatin during initial and late cycles of IP dosing.
To collect overall survival (OS) and progression-free survival (PFS) To determine changes in IP VEGF levels To determine site of first recurrence Information on CA-125 response and clinical response will be descriptive as secondary goals of this study
To estimate proportion of patients completing entire course of treatment
The Study Drugs:
Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.
Paclitaxel is designed to block the mechanisms of cell division in cancer cells, which may cause them to die.
Avastin is designed to prevent or slow down the growth of cancer cells by blocking the effects of VEGF, a blood-vessel stimulating agent that plays an important role in the growth of both normal and abnormal blood vessels.
Intraperitoneal Port (IP) Placement:
If you are found eligible to take part in this study, you will need to have an IP port, called an intraperitoneal catheter tube, placed into the abdomen. The catheter will be used to give the paclitaxel and carboplatin directly into your abdomen. You may already have had this catheter placed at a previous surgery. If not, you will have a minor surgical procedure in the operating room to have it placed. You will be asked to sign a separate surgical consent form describing this procedure, the risks involved, and the steps for taking care of the catheter while it is in place.
Study Drug Administration:
You will receive up to 6 cycles of treatment with the study drugs. Each cycle is 21 days (3 weeks) long.
You will receive paclitaxel and carboplatin through a needle in your vein on Day 1. Paclitaxel is given first followed by carboplatin. Both drugs are given over 1 hour. On Days 8 and 15 you will only receive paclitaxel by vein. This infusion is also given over 1 hour.
On Day 1, about 2 cups of normal saline will be infused into your abdomen through the IP catheter. This infusion takes 30-60 minutes. You will then receive paclitaxel through the IP port in your abdomen. When the paclitaxel infusion is complete, you will receive carboplatin through the IP port. Each infusion takes about 1 hour. After the chemotherapy infusions are complete, another 2-4 cups of normal saline will be infused through the port. This is done to help move the chemotherapy to all areas of your abdomen. You will be asked to change position frequently.
On Day 8, about 2 cups of normal saline will be infused into your abdomen through the IP catheter. You will then receive paclitaxel through the IP port in your abdomen over 1 hour. While you are receiving paclitaxel through your IP port, you will also receive Avastin by vein. The first dose of Avastin will be given over 90 minutes. If you tolerate the first infusion well, the second infusion (given in Cycle 3) may be given over 60 minutes. If the 60-minute infusion is well-tolerated, all infusions after that may be given over 30 minutes. After the paclitaxel infusion is complete, you will receive another 2-4 cups of normal saline through the port. You will be asked to change position frequently.
On Day 15, about 2 cups of normal saline will be infused into your abdomen through the IP catheter. You will then receive paclitaxel through the IP port in your abdomen. After the paclitaxel infusion is complete, you will receive another 2-4 cups of normal saline through the port. You will be asked to change position frequently.
On Day 1, about 2 cups of normal saline will be infused into your abdomen through the IP catheter. You will receive paclitaxel through the IP catheter over 1 hour. After completing paclitaxel, you will receive carboplatin through the IP catheter over 1 hour. After these infusions are complete you will receive another 2-4 cups of normal saline through the port. You will be asked to change position frequently. While undergoing IP therapy with paclitaxel and carboplatin, you will also receive the second infusion of Avastin by vein. The length of this infusion will depend how well you tolerated the drug the first time it was given in Cycle 2.
On Days 8 and 15, about 2 cups of normal saline will be infused into your abdomen through the IP catheter. You will then receive paclitaxel through the IP port in your abdomen over 1 hour. After the paclitaxel infusion is complete, you will receive another 2-4 cups of normal saline through the port. You will be asked to change position frequently.
Before you receive paclitaxel and carboplatin, you will receive the drug dexamethasone by vein to help decrease the risk of study drug side effects. You may also receive other drugs (such as cimetidine and diphenhydramine) by vein to help with side effects, such as nausea and allergic reaction. The choice of which drugs to use is up to your doctor.
On Day 1 of each cycle, the following tests and procedures will be performed:
Blood (about 1 teaspoon) will be drawn to check your CA125 level before treatment starts in Cycle 1 and on Day 1 of Cycles 2, 4, and 6.
Before treatment starts in Cycle 1 and on Day 8 of Cycle 2 and Day 1 of Cycles 3-6, urine will be collected for routine tests.
On Days 1, 8, and 15 of Cycles 1, 2, and 4, blood (1 teaspoon each time) will be drawn 12 different times each day for pharmacokinetic (PK) testing. PK testing measures the amount of study drugs in the body at different time points. Blood (1 teaspoon each time) will also be drawn 1 time on Days 2 and 3 of Cycles 1, 2, and 4.
On Day 8 of Cycle 2 and Day 1 of Cycles 3, 4, and 6 before paclitaxel starts, you will have the levels of vascular endothelial growth factor (VEGF) in your abdominal fluid measured. VEGF is a protein that causes fluid build-up (ascites) in the abdomen. About 2 cups of normal saline will be infused through the IP port. You will be asked to change positions for about 15 minutes. Then about 3-4 tablespoons of the fluid will be removed from the port with a syringe. This shows how Avastin is affecting your abdominal fluid. You will also have blood (about 1 teaspoon) drawn to check the levels of VEGF in your blood.
Length of Study:
You may remain on this study for up to 6 cycles. You will be taken off study early if the disease gets worse or intolerable side effects occur.
Once you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:
After your last study visit, you will be contacted about every 3 months from then on to check on how you are doing. You will return to the clinic (if you come to M. D. Anderson for your regular care) or researchers will call you on the phone to ask you questions about how you are doing. Your doctor will tell you if any standard tests and procedures need to be performed.
This is an investigational study. Avastin, carboplatin, and paclitaxel are FDA approved and commercially available for the treatment of many types of cancer. At this time, the addition of Avastin to paclitaxel and carboplatin is being used to treat ovarian cancer in research only.
Up to 46 patients will take part in this multicenter study. Up to 15 will be enrolled at M. D. Anderson.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Arm (s)||Experimental: Paclitaxel + Carboplatin + Avastin
Paclitaxel Cycle 1 = 60 mg/m^2 IV weekly over 1 hour x 3 weeks; Cycles 2-6 = 60 mg/m^2 IP weekly over 1 hour x 3 weeks of each cycle.
Carboplatin Cycle 1 = AUC 6 IV over 1 hour on day 1; Cycles 2-6 = AUC 6 IP over 1 hour on day 1 of each cycle.
Avastin Cycle 2 = 15 mg/kg IV over 90 minutes on day 8; Cycles 3-6 = 15 mg/kg IV on day 1 of each cycle.
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Enrollment ICMJE||46|
|Completion Date||Not Provided|
|Estimated Primary Completion Date||February 2018 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00652119|
|Other Study ID Numbers ICMJE||2007-0223, NCI-2010-00091|
|Has Data Monitoring Committee||No|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||M.D. Anderson Cancer Center|
|Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|Information Provided By||M.D. Anderson Cancer Center|
|Verification Date||August 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP