Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma

Myxofibrosarcoma Clinical Trial

Official title: A Phase I/Randomized Phase II Study of MLN0128 (TAK-228) VS. Pazopanib in Patients With Locally Advanced/Unresectable and/or Metastatic Sarcoma

Status Terminated

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of sapanisertib and to see how well it works compared to pazopanib hydrochloride in treating patients with sarcoma that is too large to be removed (locally advanced) or has spread to other areas of the body (metastatic). Sapanisertib and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the safety and maximum tolerable dose of sapanisertib (MLN0128 [TAK-228]) within this patient population. (Phase I) II. To determine the differences in progression-free survival (PFS) in patients with sarcoma who receive MLN0128 (TAK-228) as compared to pazopanib (pazopanib hydrochloride). (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate adverse events. (Phase I/II) II. To evaluate overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR). (Phase I/II) III. To evaluate time to progression (TTP) and overall survival (OS). (Phase I/II)

EXPLORATORY OBJECTIVES:

I. To evaluate PFS and secondary endpoints within patients crossing over to MLN0128 (TAK-228), upon disease progression during treatment with pazopanib. (Phase II) II. To evaluate the 4 month CBR observed within patients treated with MLN0128 (TAK-228) and grouped by histologically defined cohorts. (Phase II)

OUTLINE: This is a phase I, dose-escalation study, followed by a randomized phase II study.

PHASE I: Patients receive sapanisertib orally (PO) on days 1, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sapanisertib as in Phase I. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive pazopanib hydrochloride PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm I.

After completion of study treatment, patients are followed up at 4 weeks and then every 6 months for 2 years. ;

Related Conditions & MeSH terms

• High Grade Sarcoma
• Histiocytoma, Malignant Fibrous
• Leiomyosarcoma
• Metastatic Leiomyosarcoma
• Metastatic Malignant Peripheral Nerve Sheath Tumor
• Metastatic Synovial Sarcoma
• Metastatic Undifferentiated Pleomorphic Sarcoma
• Metastatic Unresectable Sarcoma
• Myxofibrosarcoma
• Nerve Sheath Neoplasms
• Recurrence
• Recurrent Leiomyosarcoma
• Recurrent Malignant Peripheral Nerve Sheath Tumor
• Recurrent Synovial Sarcoma
• Recurrent Undifferentiated Pleomorphic Sarcoma
• Sarcoma
• Sarcoma, Synovial
• Stage III Uterine Corpus Leiomyosarcoma AJCC v8
• Stage IIIA Uterine Corpus Leiomyosarcoma AJCC v8
• Stage IIIB Uterine Corpus Leiomyosarcoma AJCC v8
• Stage IIIC Uterine Corpus Leiomyosarcoma AJCC v8
• Stage IV Uterine Corpus Leiomyosarcoma AJCC v8
• Stage IVA Uterine Corpus Leiomyosarcoma AJCC v8
• Stage IVB Uterine Corpus Leiomyosarcoma AJCC v8
• Unresectable Leiomyosarcoma

• NCT number: NCT02601209
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 30, 2015
• Completion date: July 11, 2022