Sorafenib Tosylate and Hypoxia-Activated Prodrug TH-302 in Treating Patients With Advanced Kidney Cancer or Liver Cancer That Cannot Be Removed By Surgery

Phase 1

Completed

• Conditions: Kidney Cancer; Liver Cancer
• Interventions: Drug: hypoxia-activated prodrug TH-302; Drug: sorafenib tosylate

• Registration Number: NCT01497444
• Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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)

Secondary

* 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 Timeline

• Study First Submitted: 2011-12-20
• Study First Submitted QC: 2011-12-20
• Study First Posted: 2011-12-22
• Study Start: 2012-05
• Primary Completion: 2016-01
• Study Completion: 2019-11-01
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-04
• Last Update Posted: 2020-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
sorafenib and TH-302	sorafenib tosylate	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.
sorafenib and TH-302	hypoxia-activated prodrug 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.

Primary Outcome Measures

Name	Time	Method
Overall response rate (Phase II)	Up to 3 years
MTD of sorafenib tosylate and TH-302 (Phase I)	Up to 24 weeks
Number of dose-limiting toxicity incidents as assessed by CTCAE version 4.0 (Phase I)	Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Overall response rate based on standard RECIST criteria (Phase II)	Up to 3 years
Adverse events as assessed by NCI CTCAE version 4.0 (Phase II)	Up to 3 years
OS (Phase II)	Up to 3 years
AFP response rate (Phase II)	Up to 3 years
Duration of response based on modified (standard) RECIST criteria (Phase II)	Up to 3 years
PFS (Phase II)	Up to 3 years

Trial Locations

Locations (2)

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States

Mayo Clinic Scottsdale; 🇺🇸 Scottsdale, Arizona, United States