NCT02159989

Sapanisertib and Ziv-Aflibercept in Treating Patients With Recurrent Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Phase I Study of MLN0128 (TAK-228) (NSC# 768435) in Combination With Ziv-Aflibercept (NSC# 724770) in Patients With Advanced Cancers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 83 (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 best dose of sapanisertib and ziv-aflibercept in treating patients with solid tumors that have come back (recurrent) and have spread to another place in the body (metastatic) or cannot be removed by surgery (unresectable). Sapanisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ziv-aflibercept may stop the growth of solid tumors by blocking the growth of new blood vessels necessary for tumor growth. Giving sapanisertib with ziv-aflibercept may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate safety and tolerability, determine maximum tolerated dose (MTD) and recommend a phase II dose of the combination of MLN0128 (TAK-228) (sapanisertib) with ziv-aflibercept in patients with advanced cancers refractory to standard therapy. SECONDARY OBJECTIVES: I. To give early indication of efficacy by evaluation of tumor size. II. To evaluate v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (serine/threonine kinase) (mTOR) signaling and adaptive responses; testing phosphorylation levels of biomarkers such as, but not limited to, vascular endothelial growth factor (VEGF)1 and 2, AKT and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) following treatment with MLN0128 (TAK-228) and ziv-aflibercept in peripheral blood mononuclear cells (PBMCs) and biopsy samples during expansion cohort. OUTLINE: This is a dose-escalation study. Patients receive sapanisertib orally (PO) once daily (QD) on days 2-4, 9-11, 16-18, and 23-25 and ziv-aflibercept intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Conditions

• Advanced Malignant Solid Neoplasm
• Fibrolamellar Carcinoma
• Metastatic Malignant Solid Neoplasm
• Ovarian Carcinoma
• Pancreatic Neuroendocrine Tumor
• Recurrent Malignant Solid Neoplasm
• Refractory Malignant Solid Neoplasm
• Unresectable Solid Neoplasm

Interventions

Type	Name	Description
DRUG	Sapanisertib	Given PO
BIOLOGICAL	Ziv-Aflibercept	Given IV

Timeline

• Start date: 2014-06-18
• Primary completion: 2021-06-29
• Completion: 2024-01-29
• First posted: 2014-06-10
• Last updated: 2025-10-20
• Results posted: 2025-10-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study