A Single Arm, Phase Ib/II Trial of Single Agent Pacritinib in Patients With 1q21.3 Amplified Solid Tumors Enriching for Interleukin-1 Receptor-associated Kinase 1 Pathway Activation (PAIR)

Breast Cancer Clinical Trial

Official title: A Single Arm, Phase Ib/II Trial of Single Agent Pacritinib in Patients With 1q21.3 Amplified Solid Tumors Enriching for Interleukin-1 Receptor-associated Kinase 1 (IRAK1) Pathway Activation (PAIR)

Status Recruiting

Clinical Trial Summary

This is a single arm, open-label, lead in phase Ib dose confirmation, followed by phase II study with 2 parallel study cohorts. Patients will be pre-screened for presence of 1q21.3 copy number amplification in plasma samples prior to screening process. Only patients with confirmed plasma cell-free DNA (cfDNA) 1q21.3 copy number amplification who successfully meet study eligibility criteria will be enrolled.

The phase Ib segment will be carried out in a standard 3+3 design, with a projected enrolment of 3 to 18 patients to determine the RP2D. In the phase II portion, 2 parallel cohorts will be enrolled (Cohort A: 1q21.3 amplified breast cancers, Cohort B: 1q21.3 amplified other solid tumors). Based on the Simon 2 stage optimal design, 12 patients will be enrolled in each cohort for stage I of the study, and assessed for PFS. If at least 3 of 12 patients meet study response criteria, the study will then be expanded to stage 2 to include a total of 25 patients in each cohort. Accounting for 10% attrition rate, a maximum of 28 patients will be enrolled into each cohort for phase II of the study.

Clinical Trial Description

2.1. Hypothesis

• Single agent pacritinib is effective in disease control of patients with 1q21.3 amplified solid tumors

• Single agent pacritinib is safe in patients with 1q21.3 amplified solid tumors

• Treatment with pacritinib will decrease plasma cfDNA copy number ratio of 1q21.3 in patients with 1q21.3 amplified solid tumors

• Plasma cfDNA copy number ratio of 1q21.3 will correlate with serial radiological findings in patients with 1q21.3 amplified solid tumors

2.2. Primary Objectives

• To determine the proportion of patients with 1q21.3 amplified breast cancer (primary population: Cohort A) who remain progression-free at 4 months after treatment with pacritinib

2.3. Secondary Objectives

• To determine the safety and tolerability of pacritinib in patients with treatment refractory solid tumors

• To determine the RP2D of pacritinib in patients with treatment refractory solid tumors

• To evaluate disease response from pacritinib by RECIST criteria version 1.1 and tumor markers

• To determine the proportion of patients with 1q21.3 amplified treatment refractory solid tumors excluding (exploratory population: Cohort B) who remain progression-free at 4 months after treatment with pacritinib

2.4. Exploratory Objectives

• To determine pharmacokinetic (PK) parameters including Cmax/min and steady state concentrations of pacritinib through serial plasma sampling

• To determine pharmacodynamics (PD) parameters including highly sensitive C-reactive protein (CRP), HbA1c, changes in cytokine levels and plasma cfDNA levels of copy number ratio of 1q21.3

• Correlation of plasma cfDNA levels of copy number ratio of 1q21.3 with radiological findings determined by RECIST criteria 1.1 and tumor markers ;

Related Conditions & MeSH terms

• Breast Cancer

• NCT number: NCT04520269
• Study type: Interventional
• Source: National University Hospital, Singapore
• Contact: Joline Si Jing Lim
• Phone: 6779 5555
• Email: joline_sj_lim@nuhs.edu.sg
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 13, 2020
• Completion date: July 2023