NCT04520269

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)

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: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 21 Years – 99 Years
• Healthy volunteers: Not accepted

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.

Detailed 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

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	Pacritinib	3+3 design Dose Level 1 :200mg BD every 4 weeks Dose Level -1 :200mg OM, 100mg ON every 4 weeks Dose Level -2 :100mg BD every 4 weeks

Timeline

• Start date: 2020-07-13
• Primary completion: 2026-07-01
• Completion: 2026-07-01
• First posted: 2020-08-20
• Last updated: 2025-09-25

Locations

1 site across 1 country: Singapore