Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver

Unresectable Hepatocellular Carcinoma Clinical Trial

Official title: A Phase 2 Study of Pevonedistat in Combination With Carboplatin and Paclitaxel in Advanced Intrahepatic Cholangiocarcinoma

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies how well pevonedistat alone or in combination with chemotherapy (paclitaxel and carboplatin) works in treating patients with bile duct cancer of the liver. Pevonedistat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study may help the study doctors find out how well pevonedistat shrinks bile duct cancer of the liver when given alone and when in combination with paclitaxel and carboplatin.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the objective response rate of pevonedistat as a single agent and in combination with carboplatin and paclitaxel in patients with unresectable intrahepatic cholangiocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of pevonedistat alone and in combination with carboplatin and paclitaxel in patients with intrahepatic cholangiocarcinoma.

II. To determine the clinical benefit rate of patients with advanced intrahepatic cholangiocarcinoma (ICC) treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel.

III. To determine progression-free survival of patients treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel.

IV. To determine overall survival of patients treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel.

EXPLORATORY OBJECTIVES:

I. To determine whether overexpression of NEDD8, NAE1, and UBC12 predict response to treatment.

II. To identify the mutation profile of those cholangiocarcinomas with overexpression of the neddylation pathway.

III. To bank specimens for further future investigations.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive pevonedistat intravenously (IV) over 60 minutes on days 1, 3, and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive pevonedistat IV over 1 hour on days 1, 3, and 5, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 15-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Starting cycle 5, patients may receive pevonedistat monotherapy at the discretion of treating physician.

After completion of study treatment, patients are followed up at 30 days after last dose of study treatment, then every 3 months for the first year and every 6 months for years 2-3. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Cholangiocarcinoma
• Metastatic Cholangiocarcinoma
• Metastatic Hepatocellular Carcinoma
• Stage III Hepatocellular Carcinoma AJCC v8
• Stage III Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IIIA Hepatocellular Carcinoma AJCC v8
• Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IIIB Hepatocellular Carcinoma AJCC v8
• Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IV Hepatocellular Carcinoma AJCC v8
• Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IVA Hepatocellular Carcinoma AJCC v8
• Stage IVB Hepatocellular Carcinoma AJCC v8
• Unresectable Cholangiocarcinoma
• Unresectable Hepatocellular Carcinoma
• Unresectable Intrahepatic Cholangiocarcinoma

• NCT number: NCT04175912
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 16, 2020
• Completion date: October 1, 2024