Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)
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|ClinicalTrials.gov Identifier: NCT01183663|
Recruitment Status : Completed
First Posted : August 17, 2010
Last Update Posted : June 3, 2016
|First Submitted Date ICMJE||August 13, 2010|
|First Posted Date ICMJE||August 17, 2010|
|Last Update Posted Date||June 3, 2016|
|Study Start Date ICMJE||August 2010|
|Actual Primary Completion Date||May 2016 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) [ Time Frame: First 21/28 day cycle ]
If more than 33% of patients enrolled in any particular dose level develop dose limiting toxicity (DLT), treatment will continue at dose level immediately below. If not more than 33% of patients in cohort develop DLT, this cohort considered the MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity, as defined in most current version of NCI CTCAE, even if expected and believed related to study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens, or alopecia), any Grade 4 hematologic toxicity lasting at least 7 days or longer, despite supportive care or associated with bleeding and/or sepsis; any Grade 4 nausea or vomiting lasting > 5 days despite maximum anti-nausea regimens and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome, but excluding alopecia; or any severe or life-threatening complication or abnormality not covered in NCI CTCAE.
|Original Primary Outcome Measures ICMJE
||Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) [ Time Frame: Each cycle (21/28 days) ]|
|Change History||Complete list of historical versions of study NCT01183663 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Tumor Response [ Time Frame: 4 months ]
Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e., decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.
|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||Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)|
|Official Title ICMJE||A Phase I Study of Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-fluorouracil, Leucovorin, Oxaliplatin (FOLFOX) in Patients With Advanced Cancers|
|Brief Summary||The goal of this clinical research study is to find the highest tolerable doses of the combinations of lenalidomide and other drugs that can be given to patients with advanced cancer. The safety of the drug combinations will also be studied.|
The Study Drugs:
Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. This may decrease or prevent the growth of cancer cells.
Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth. This may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.
Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.
Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells to die.
FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) is a drug combination designed to kill rapidly dividing cells by stopping DNA (the genetic material of cells) from duplicating. Because of a pharmacy shortage of IV leucovorin, patients will continue treatment without leucovorin until it becomes available.
Study Groups (Arms):
If you are found to be eligible to take part in this study, you will be assigned to 1 of 4 study arms. Each study arm will receive lenalidomide in combination with 1 of the 4 drugs/drug combinations described in the "Study Drugs" section above. The arm you are assigned to will depend on what arms are still open and what your doctor thinks is appropriate for you. Your doctor will consider the type of disease you have, other drugs you have received for the disease, and any side effects you may have seen with other drugs when deciding which arm you should be assigned to:
Up to 4 dose levels of the drug combination will be tested for each arm. Up to 6 participants will be enrolled at each dose level in each arm. For each arm, the first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose for the drug combination is found for each arm. After the highest tolerable dose of the drug combination is found, an additional 20 patients will be able to receive this combination dose in each arm.
Study Drug Administration:
If you are in Arm 1, 2, or 3, each study "cycle" will be 28 days. If you are in Arm 4, each study cycle will be 21 days.
If you are in Arms 1, 2, or 3, you will take lenalidomide by mouth 1 time each day during Days 1-21 of each study cycle. If you are in Arm 4, you will take lenalidomide by mouth 1 time each day during Days 1-14 of each study cycle. Swallow lenalidomide capsules whole with 1 cup (about 8 ounces) of water. Do not break, chew, or open the capsules.
If you miss a dose of lenalidomide, take is as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact the study staff right away. Women who are able to become pregnant that might be caring for you should not touch the lenalidomide capsules or bottles unless they are wearing gloves. Any unused Revlimid® (lenalidomide) should be returned as instructed through the RevAssist® program.
You will receive bevacizumab by vein on Days 1 and 15 of each cycle. The first time you receive bevacizumab, it will be given over 90 minutes. If you tolerate it well, the rest of the doses will be given over 30-60 minutes.
You will take sorafenib by mouth 1 time each day of every cycle (Days 1-28). You should take it with a cup (8 ounces) of water, after taking lenalidomide. You should not eat or drink anything other than water for at least 1 hour before or after taking sorafenib.
You will receive temsirolimus by vein over 30-60 minutes on Days 1, 8, 15, and 22 of each cycle.
You will receive oxaliplatin and leucovorin by vein over 2 hours on Day 1 of each cycle. You will also receive 5-FU by vein over 22 hours at home on Days 1-2. The drug will be given through a pump that you carry with you.
At all study visits, you will be asked about any side effects you may be having and about any other drugs you may be receiving.
On Day 1 of Cycle 1, the following tests and procedures will be performed if they were not performed within 7 days before Day 1 of Cycle 1:
On Day 15 of Cycle 1, blood (about 1 tablespoon ) will be drawn for routine tests.
On Day 1 of every even numbered cycle (Cycles 2, 4, 6, and so on):
At the end of every even numbered cycle (Day 28 for Arms 1, 2, and 3; Day 21 for Arm 4):
On Day 1 of every odd numbered cycle (Cycles 3, 5, 7, and so on):
If you are a woman who is able to become pregnant, you will have blood (about 1 teaspoon) or urine pregnancy tests on Day 1 of every cycle, 1 time each week during the first cycle, when you stop taking the study drugs, and 30 days after you stop taking the study drugs.
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.
Thirty (30) days after you stop taking the study drugs for any reason, the following tests and procedures will be performed:
This is an investigational study. All of the study drugs are FDA-approved and commercially available for use in various types of cancer:
It is investigational to give lenalidomide in combination with each of the other drugs to patients with advanced cancer.
Up to 180 participants will take part in this study. All will be enrolled at MD Anderson.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Advanced Cancers|
|Study Arms ICMJE||
|Publications *||Ganesan P, Piha-Paul S, Naing A, Falchook G, Wheler J, Fu S, Hong DS, Kurzrock R, Janku F, Laday S, Bedikian AY, Kies M, Wolff RA, Tsimberidou AM. Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer. Invest New Drugs. 2014 Apr;32(2):279-86. doi: 10.1007/s10637-013-9966-3. Epub 2013 Jun 12.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||May 2016|
|Actual Primary Completion Date||May 2016 (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||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01183663|
|Other Study ID Numbers ICMJE||2010-0108
NCI-2012-01790 ( Registry Identifier: NCI CTRP )
|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||June 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP