Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease
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|ClinicalTrials.gov Identifier: NCT01864070|
Recruitment Status : Withdrawn
First Posted : May 29, 2013
Last Update Posted : July 22, 2014
|First Submitted Date ICMJE||May 23, 2013|
|First Posted Date ICMJE||May 29, 2013|
|Last Update Posted Date||July 22, 2014|
|Study Start Date ICMJE||May 2014|
|Estimated Primary Completion Date||May 2018 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Dose Limiting Toxicities (DLT) for Combination of TheraSphere and Everolimus [ Time Frame: 56 days ]
Dose limiting toxicity (DLT) defined as any toxicity occurring during the first 56 days of therapy with definite, possible or probable attribution to TheraSphere and/or Everolimus and meets CTCAE version 4.0 criteria.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01864070 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease|
|Official Title ICMJE||Phase I Study of TheraSphere and Everolimus Among Patients With Neuroendocrine Tumors and Liver Only or Liver Dominant Disease|
The goal of this clinical research study is to find the highest tolerable dose of the combination of everolimus with TheraSphere that can be given to patients with advanced NETs that have spread to the liver. The safety of everolimus and TheraSphere will also be studied.
Everolimus is designed to block a protein inside the cancer cells, which is also involved in cancer growth.
TheraSphere is a medical device containing a radioactive material called yttrium-90 (Y-90). Tiny glass beads called microspheres are filled with Y-90 and then injected through an artery directly into the liver. This allows a large dose of radiation to be given directly to the tumor, which may lower the risk of side effects from the radiation to other parts of the body and/or to healthy liver tissue. The radiation from TheraSphere stays in the body and begins to lose its effect within 12 days. The glass microspheres will stay in the body from that point on. The radiation will eventually decay (go away). By the time a participant leaves the hospital, the amount of radiation outside of the body will be low enough to not be a threat to others.
If patient is are found to be eligible to take part in this study, they will be assigned to a dose level of everolimus based on when they joined this study. Up to 3 dose levels of everolimus will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the low dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. If intolerable side effects are seen, the dose may be lowered. This will continue until the highest tolerable dose of everolimus is found. After that, 10 additional participants will be enrolled at the highest tolerable dose that was found.
All participants will receive the same dose level of TheraSphere.
Study Drug Administration:
Each study cycle is 28 days.
On Day 1 of Cycle 1, 2 weeks before the TheraSphere procedure, patient will start taking everolimus.
Patient will take 1-2 tablets of everolimus by mouth 1 time every day. Patient will take the everolimus tablets with a glass of water in the morning at the same time every day. The tablets should be swallowed whole and not chewed or crushed. The tablets may be taken either always with or always without food.
If patient vomits after taking their dose, they should not take another tablet that day. It is very important that patients take the tablets given to them just as the study doctor tells them and that they do not miss any tablets. If patient does forget to take it one day, they should not take any extra doses the next day. Instead, patient should contact their doctor and ask for advice.
On the days of patient's study visits, they should take their dose of everolimus at the clinic, not at home.
About 2 weeks before the TheraSphere procedure, patient will have an angiogram. An angiogram is an imaging test that uses contrast dye to help the doctor look at the body's blood vessels. Patient will be given drugs by vein in their arm or hand to help them relax, but patient will stay awake during the procedure. An area in patient's groin will be numbed with anesthetic.
During the procedure, the doctor will insert a catheter into a blood vessel in patient's groin that leads to their liver. Dye will be injected into the catheter, and a series of x-rays will be taken that will allow the doctor to see the blood vessels in patient's liver. At the end of the procedure, the catheter will be removed from patient's groin area. The x-rays taken will be looked at by patient's doctor to plan for their TheraSphere procedure. The angiogram procedure should take about 1½ to 3 hours.
On Day 15 of Cycle 1, patient will receive TheraSphere. Before the procedure, patient will be given drugs by vein in their arm or hand to help them relax, but patient will stay awake during the procedure. An area in patient's groin will be numbed with anesthetic. Patient may ask the study staff for information about how the anesthesia drugs are given and their risks.
The doctor will insert a catheter into a blood vessel in patient's groin that leads to their liver. Based on the planning from patient's angiogram procedure, the doctor will guide the catheter to the target blood vessel. Once the catheter is in the proper blood vessel, the TheraSphere microspheres containing Y-90 will be injected into the catheter to reach the tumor in the liver. After the TheraSphere microspheres are injected, the catheter will be removed from patient's groin. The entire procedure will take about 1½ to 3 hours.
After receiving the TheraSphere microspheres, patient will stay in the recovery area for several hours so that the staff can check patient for possible side effects. If patient has any serious side effects, they may be admitted to the hospital to be checked on and for treatment, if needed.
Before all visits, patient must fast starting at midnight the night before.
On Day 1 of Cycle 1, if the tests have not been done in the last 5 days:
On Day 14 or 15 of Cycle 1:
On Day 1 of Cycles 2 and beyond:
On Day 1 of Cycles 2 and 3 and every 3-6 weeks after that, blood (about 2 teaspoons) will be drawn to check for hepatitis B and/or C if the doctor thinks it is needed.
On Day 1 of Cycles 2, 4, and every 3 cycles after that, blood (about 2 tablespoons) will be drawn for tumor marker testing and additional routine tests.
On Day 1 of Cycles 4 and beyond, urine will be collected for routine tests.
On Day 1 of Cycle 4 and every 3 cycles after that, patient will have a CT scan, MRI, and/or x-ray to check the status of the disease.
Length of Dosing:
Patient will receive TheraSphere on Day 15 of Cycle 1 and they may continue taking everolimus for up to 12 cycles, as long as the doctor thinks it is in patient's best interest. Patient will no longer be able to take everolimus if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.
Patient's participation on the study will be over once they have completed the follow-up.
Within 1 week after patient stops taking the study drug, the following tests and procedures will be performed. Patient must fast starting at midnight the night before this visit.
At least 1 time a week by phone or at the clinic for up to 30 days after patient's last everolimus dose, the study staff will follow up with patient. Patient will be asked about any side effects they may have had. The call should last about 10-15 minutes.
If patient left the study because of a side effect, they will continue to be contacted by the study staff until the side effect has gone away or become stable.
This is an investigational study. Everolimus is commercially available and FDA approved to treat advanced pancreatic NETs and other types of cancer. The combination of everolimus and TheraSphere in this study is investigational.
TheraSphere is commercially available and FDA approved as a radiation treatment for liver cancer. The use of TheraSphere in this study is investigational.
Up to 22 participants will be enrolled in this study. All will take part at MD Anderson.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Liver Cancer|
|Study Arms ICMJE||Experimental: TheraSphere + Everolimus
Each cycle is 28 days. Target dose of TheraSphere is fixed at 120 Gy to entire tumor bearing portion of liver given at a single session on Cycle 1 Day 15. The dose of everolimus will be escalated in 2 sequential cohorts of 6 TheraSphere-treated patients each. Starting dose of everolimus is 5 mg by mouth daily for cycles 1 and 2. Patients will receive standard dose of Everolimus at 10 mg PO daily starting cycle 3 day 1.
Once DLT is defined or dose level 2 has been completed, a dose expansion cohort of 10 patients with advanced low to intermediate grade neuroendocrine tumor will be enrolled.
At least 1 time a week by phone or at the clinic for up to 30 days after last everolimus dose, study staff will follow up. Patient asked about any side effects they may have had.
|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||Withdrawn|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Study Completion Date ICMJE||Not Provided|
|Estimated Primary Completion Date||May 2018 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Not Provided|
|Removed Location Countries||United States|
|NCT Number ICMJE||NCT01864070|
|Other Study ID Numbers ICMJE||2011-1205|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||M.D. Anderson Cancer Center|
|Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|PRS Account||M.D. Anderson Cancer Center|
|Verification Date||July 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP