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)

NCT04520269 | Active Not Recruiting Phase 1

• 1 other identifier: MC02/04/19
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

1q21.3; interleukin-1 receptor-associated kinase 1; Pacritinib; IRAK1

Outcome Measures

Primary Outcomes (3)

• Overall radiological response rate

  Rates of radiological response (complete and partial clinical response), including confidence intervals. measured by RECIST 1.1

  36 months

• Progression-free survival

  Proportion of patients in cohort A and Cohort B who remain progression-free at 4 months

  36 months

• Overall safety of pacritinib in patients with treatment refractory solid tumors

  Safety measures that will be used in the study include physical examinations and clinical laboratory tests (haematology and blood chemistries). Patients will be rated for toxicity during each cycle of treatment using the NCI CTCAE scale, version 4.03

  36 months

Study Arms (1)

Patient with (cfDNA) 1q21.3 copy number amplification

EXPERIMENTAL

The phase Ib segment will be carried out in a standard 3+3 design. 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).

Drug: Pacritinib

Interventions

Pacritinib DRUG

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

Patient with (cfDNA) 1q21.3 copy number amplification

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be included in the study only if they meet all of the following criteria:
• Age \> or = 21 years.
• Histological or cytological diagnosis of malignant advanced solid tumors refractory to standard therapy or for which no suitable effective standard therapy exists.
• o Patients who fit above criteria will be pre-screened for presence of 1q21.3 amplification using a plasma assay based on digital PCR. Patients with tumors that exhibit 1q21.3amplification will be enrolled. Positive 1q21.3 amplification is defined as more than 3 standard deviations above the mean comparing the averaged copy number ratio of 3 genes (TUFT1, S100A8 and S100A7) relative to the reference gene RPP30 measure in sample (13).
• ECOG 0-2
• Has measureable or evaluable disease based on RECIST 1.1 criteria
• Estimated life expectancy of at least 12 weeks.
• Has documented progressive disease from last line of therapy
• Has recovered from acute toxicities from prior anti-cancer therapies
• Adequate organ function including the following:
• Bone marrow:
• Absolute neutrophil (segmented and bands) count (ANC) \> or = 1.5 x 109/L
• Platelets \> or = 100 x 109/L
• Hemoglobin \> or = 8 x 109/L
• Hepatic:

You may not qualify if:

• Patients will be excluded from the study for any of the following reasons:
• Treatment within the last 30 days with any investigational drug.
• Concurrent administration of any other tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
• Major surgery within 28 days of study drug administration.
• Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Pregnancy.
• Breast feeding.
• Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
• Significant recent bleeding history defined as CTCAE grade 2 or higher within the past 3 months, unless precipitated by an inciting event (e.g. surgery, trauma, injury).
• Suboptimal cardiac function, defined by:
• Any history of CTCAE grade \> or = 2 non-dysrhythmia cardiac conditions within the last 6 months
• New York Heart Association class II, III or IV congestive cardiac failure
• Left ventricular ejection fraction of \<45%
• QTc prolongation of \>450ms as assessed by ECG or other factors that increase the risk of QT interval prolongation
• Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (2)

• 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.

  PMID: 30627694 BACKGROUND

• 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.

  PMID: 12473512 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Joline Si Jing Lim

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single arm, open-label, lead in phase Ib dose confirmation, followed by phase II study with 2 parallel study cohorts.

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 20, 2020
• Study Start: July 13, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)