Sorafenib Tosylate and Hypoxia-Activated Prodrug TH-302 in Treating Patients With Advanced Kidney Cancer or Liver Cancer That Cannot Be Removed By Surgery
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01497444|
Recruitment Status : Active, not recruiting
First Posted : December 22, 2011
Last Update Posted : February 27, 2018
RATIONALE: Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth by blocking blood flow to the tumor. Drugs used in chemotherapy, such as hypoxia-activated prodrug TH-302, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 may kill more tumor cells.
PURPOSE: This phase I/II trial studies the side effects and best dose of giving sorafenib tosylate together with hypoxia-activated prodrug TH-302 and to see how well they work in treating patients with advanced kidney cancer or liver cancer that cannot be removed by surgery.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Cancer Liver Cancer||Drug: hypoxia-activated prodrug TH-302 Drug: sorafenib tosylate||Phase 1|
- To determine the maximum-tolerated dose (MTD) and recommended Phase II dosing (RP2D) for the combination of sorafenib tosylate and hypoxia-activated prodrug TH-302 (TH-302) in patients with hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC; non-HCC) advanced solid tumors. (Phase I)
- To evaluate the overall response rate (RR) determined based on modified RECIST criteria (Lencioni and Llovet 2010) in patients with advanced HCC receiving sorafenib tosylate with TH-302. (Phase II)
- To characterize overall toxicity profile of sorafenib tosylate + TH-302 within patients with HCC and RCC (non-HCC) advanced solid tumors. (Phase I)
- To characterize the responses of sorafenib tosylate + TH-302 within patients with HCC and RCC (non-HCC) advanced solid tumors. (Phase I)
- To assess the adverse events (AEs) profile and safety profile of sorafenib tosylate in combination with TH-302 in patients with advanced HCC. (Phase II)
- To estimate the overall response rate based on standard RECIST criteria in the study population. (Phase II)
- To estimate the duration of response based on modified (standard) RECIST criteria in the study population. (Phase II)
- To estimate the progression free survival (PFS) in the study population. (Phase II)
- To estimate the overall survival (OS) in the study population. (Phase II)
- To estimate the alpha-fetoprotein (AFP) response rate (defined as > 20% decrease of AFP from baseline) in the study population. (Phase II)
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.
Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-28 and hypoxia-activated prodrug TH-302 IV over 30 minutes on days 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood sample collection periodically during study for alpha-fetoprotein analysis.
After completion of study treatment, patients are followed up for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Study of Sorafenib + TH-302: Phase I in Advanced Renal Cell Carcinoma (RCC) and Advanced Hepatocellular Carcinoma (HCC) and Phase II in 1st Line Advanced HCC|
|Study Start Date :||May 2012|
|Actual Primary Completion Date :||January 2016|
Experimental: sorafenib and TH-302
Patients will be administered sorafenib tablets to take twice daily by mouth, every day of each cycle. Patients will also be given TH-302 intravenously (IV) on days 8, 15 and 22 of each cycle. A cycle is 28 days.
Drug: hypoxia-activated prodrug TH-302
Drug: sorafenib tosylate
- Number of dose-limiting toxicity incidents as assessed by CTCAE version 4.0 (Phase I) [ Time Frame: Up to 24 weeks ]
- MTD of sorafenib tosylate and TH-302 (Phase I) [ Time Frame: Up to 24 weeks ]
- Overall response rate (Phase II) [ Time Frame: Up to 3 years ]
- Adverse events as assessed by NCI CTCAE version 4.0 (Phase II) [ Time Frame: Up to 3 years ]
- Overall response rate based on standard RECIST criteria (Phase II) [ Time Frame: Up to 3 years ]
- Duration of response based on modified (standard) RECIST criteria (Phase II) [ Time Frame: Up to 3 years ]
- PFS (Phase II) [ Time Frame: Up to 3 years ]
- OS (Phase II) [ Time Frame: Up to 3 years ]
- AFP response rate (Phase II) [ Time Frame: Up to 3 years ]
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): NCT01497444
|United States, Arizona|
|Mayo Clinic Scottsdale|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Mitesh J. Borad, MD||Mayo Clinic|