A Two-Dimensional Dose-Finding Study of Ixazomib in Combination With Gemcitabine and Doxorubicin, Followed by a Phase II Extension to Assess the Efficacy of This Combination in Metastatic, Surgically Unresectable Urothelial Cancer
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|ClinicalTrials.gov Identifier: NCT02420847|
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Last Update Posted : July 20, 2018
This clinical research study is made up of 2 phases.
The goal of Phase 1 of this study is to learn the highest tolerated dose of the combination of ixazomib, gemcitabine, and doxorubicin that can be given to patients with urothelial cancer.
The goal of Phase 2 of this study is to learn if the combination of ixazomib, gemcitabine, and doxorubicin can help to control urothelial cancer.
The safety of the drug combinations will be studied in both phases.
This is an investigational study. Ixazomib is not FDA approved or commercially available for the treatment of urothelial cancer. Gemcitabine and doxorubicin are FDA approved and commercially available for several other types of cancer. Their use in combination with ixazomib in urothelial cancer is investigational.
The study doctor can explain how the study drugs are designed to work.
Up to 57 participants will be enrolled in this study. All will take part at MD Anderson.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer||Drug: Ixazomib Drug: Gemcitabine Drug: Doxorubicin||Phase 1 Phase 2|
Hide Detailed Description
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 6 groups of up to 4 participants will be enrolled in Phase 1 of the study, and up to 33 participants will be enrolled in Phase 2.
If you are enrolled in Phase 1, the combination dose of ixazomib, gemcitabine, and doxorubicin you receive will depend on when you join this study. The first group of participants will receive the lowest combination dose level. Each new group will receive a higher dose of the drug combination than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the drug combination is found.
If you are enrolled in Phase 2, you will receive the drug combination at the highest dose that was tolerated in Phase 1.
Study Drug Administration:
On Day 1 of every 14-day cycle, you will take ixazomib 1 time by mouth, receive gemcitabine by vein over about 90 minutes, and receive doxorubicin by vein over 15-30 minutes.
Gemcitabine and doxorubicin may be given through a catheter. A catheter is a sterile flexible tube that will be placed into a large vein while you are under anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.
You should not chew, break, or open the capsules of ixazomib. If the capsules break, be careful not to spread their dust while cleaning it up. The product may be harmful to breathe in, swallow, or touch. Gloves and protective clothing should be worn during cleanup and return of broken capsules and powder to minimize skin contact.
The area should be ventilated and the site washed with soap and water after material pick-up is complete. The material should be disposed of as hazardous medical waste in compliance with federal, state, and local regulations.
In case of contact with the powder (such as from a broken capsule), skin should be washed right away with soap and large amounts of water for at least 15 minutes. In case of contact with the eyes, large amounts of water should be used to flush the eyes for at least 15 minutes. Call the study staff right away if this happens.
On Day 1 of each cycle:
- You will have a physical exam.
- Blood (about 3-4 tablespoons) will be drawn for routine tests.
- Every 3 cycles starting with Cycle 4 (Cycles 4, 7, 10, and so on), you will also have an x-ray and CT scans or MRIs to check the status of the disease.
On Day 8 of Cycles 1 and 2, blood (about 3-4 tablespoons) will be drawn for routine tests.
If the disease gets worse, you will have either an ECHO or MUGA scan to check your heart function, if your doctor thinks it is needed.
At any time that the doctor thinks it is needed, you will have a bone scan to check the status of the disease.
Length of Treatment:
You may continue receiving the study drugs for as long as the doctor thinks it is in your best interest. You may no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Two-Dimensional Dose-Finding Study of Ixazomib in Combination With Gemcitabine and Doxorubicin, Followed by a Phase II Extension to Assess the Efficacy of This Combination in Metastatic, Surgically Unresectable Urothelial Cancer|
|Actual Study Start Date :||July 3, 2015|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||July 2022|
Experimental: Ixazomib + Gemcitabine + Doxorubicin
Starting dose of Ixazomib 4.0 mg by mouth on Day 1 of every 14-day cycle. Starting dose of Gemcitabine 10 mg/m2/min by vein on Day 1 of each 14 day cycle.
Starting dose of Doxorubicin 33 mg/m2 by vein on Day 1 of each 14 day cycle.
Phase II Starting doses of Ixazomib, Gemcitabine, and Doxorubicin is maximum tolerated dose (MTD) from Phase I.
Phase I Starting Dose of Ixazomib: 4.0 mg by mouth on Day 1 of every 14-day cycle.
Phase II Starting Dose of Ixazomib: MTD from Phase I.
Phase I Starting Dose of Gemcitabine: 10 mg/m2/min by vein on Day 1 of each 14 day cycle.
Phase II Starting Dose of Gemcitabine: MTD from Phase I.
Phase I Starting Dose of Doxorubicin: 33 mg/m2 by vein on Day 1 of each 14 day cycle.
Phase II Starting Dose of Doxorubicin: MTD from Phase I.
- Maximum Tolerated Doses (MTDs) for Combination of Ixazomib and Gemcitabine/Doxorubicin [ Time Frame: 14 days ]Maximum tolerated doses (MTDs) identified for the combination therapy of Ixazomib and Gemcitabine/Doxorubicin (i.e. dose pairs that have an acceptable target toxicity rate of 30%). Gemcitabine and Doxorubicin are given together thus considered as one combination-dose in the study design. NCI-CTCAE v4.0 criteria used for assessment of toxicity.
- Objective Response [ Time Frame: 6 weeks ]Complete response defined as resolution of all cancer related symptoms, normalization of tumor markers, and disappearance of radiographic evidence of disease. Partial response defined as a ≥ 50% decrease in disease volume with no evidence of progression in any site. Overall patient success (Major Response) requires ≥ 90% reduction of tumor volume that is sustained, with no evidence of progression after initial response. In addition, all cancer-related symptoms must be resolved. Progressive disease defined as a ≥ 25% increase in tumor volume from baseline.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02420847
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Arlene Siefker-Radtke, MD||M.D. Anderson Cancer Center|