NCT02143401

Navitoclax and Sorafenib Tosylate in Treating Patients With Relapsed or Refractory Solid Tumors

A Phase I Trial of ABT-263 (Navitoclax), a Bcl-2 Inhibitor, and Sorafenib (Nexavar) in Patients With Relapsed or Refractory Solid Organ Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and the best dose of navitoclax when given together with sorafenib tosylate in treating patients with solid tumors that have returned (relapsed) or do not respond to treatment (refractory). Navitoclax and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of the combination of navitoclax and sorafenib tosylate (sorafenib) in patients with advanced solid tumors. (Dose escalation cohort) II. To better characterize the toxicity profile of the combination of navitoclax and sorafenib. (Dose expansion cohort) SECONDARY OBJECTIVES: I. To identify any activity of this treatment combination in patients with metastatic cancer. (Dose escalation cohort) II. To seek preliminary evidence of activity of this treatment combination in patients with hepatoma. (Dose expansion cohort) CORRELATIVE OBJECTIVES: I. To determine whether the combination of navitoclax and sorafenib induces apoptosis that can be detected by peripheral blood biomarker analysis. (Dose escalation cohort) II. To assess peripheral blood biomarkers and pharmacokinetics in a more homogenous population. (Dose expansion cohort) III. To determine whether treatment is associated with Mcl-1 down regulation in hepatocellular carcinoma (HCC) at the maximum tolerated dose (MTD). (Dose expansion cohort) IV. To assess in a preliminary fashion whether pretreatment tumor cell levels of Mcl-1 predict response to this regimen through serial biopsies. (Dose expansion cohort) OUTLINE: This is a dose-escalation study of navitoclax. Patients receive navitoclax orally (PO) once daily (QD) on days 1-21 (days 1-28 cycle of 1 only) and sorafenib tosylate PO twice daily (BID) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Conditions

• Cirrhosis
• Hepatitis B Infection
• Hepatitis C Infection
• Metastatic Malignant Solid Neoplasm
• Recurrent Hepatocellular Carcinoma
• Recurrent Malignant Solid Neoplasm
• Refractory Malignant Neoplasm
• Stage IV Hepatocellular Carcinoma AJCC v7
• Unresectable Solid Neoplasm

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Navitoclax	Given PO
OTHER	Pharmacological Study	Correlative studies
DRUG	Sorafenib	Given PO
DRUG	Sorafenib Tosylate	Given PO

Timeline

• Start date: 2015-01-30
• Primary completion: 2022-11-30
• Completion: 2024-03-21
• First posted: 2014-05-21
• Last updated: 2024-11-22

Locations

10 sites across 1 country: United States