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
|ClinicalTrials.gov Identifier: NCT02420847|
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Last Update Posted : May 10, 2019
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|
Show Detailed Description
|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.
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|