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)

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.

Timeline

Start

2020-07-13

Primary completion

2026-07

Completion

2026-07

Publications

• Results Caswell-Jin JL, Plevritis SK, Tian L, Cadham CJ, Xu C, Stout NK, Sledge GW, Mandelblatt JS, Kurian AW. Change in Survival in Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review. JNCI Cancer Spectr. 2018 Nov;2(4):pky062. doi: 10.1093/jncics/pky062. Epub 2018 Dec 24.
• Results Crown J, Dieras V, Kaufmann M, von Minckwitz G, Kaye S, Leonard R, Marty M, Misset JL, Osterwalder B, Piccart M. Chemotherapy for metastatic breast cancer-report of a European expert panel. Lancet Oncol. 2002 Dec;3(12):719-27. doi: 10.1016/s1470-2045(02)00927-0.

Drugs

Indications