Status:
ACTIVE_NOT_RECRUITING
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)
Lead Sponsor:
National University Hospital, Singapore
Conditions:
Breast Cancer
Eligibility:
All Genders
21-99 years
Phase:
PHASE1
PHASE2
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 amplifi...
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 tumo...
Eligibility Criteria
Inclusion
- 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:
- Bilirubin \< or = 1.5 x upper limit of normal (ULN),
- ALT or AST \< or = 2.5x ULN, (or \< or = 5 X with liver metastases)
- Renal:
- Creatinine \< or = 1.5x ULN
- Signed informed consent from patient
- Able to comply with study-related procedures.
- Prior therapy (patients enrolled in phase Ib may be enrolled if they fulfil prior therapy criteria for either Cohort A or Cohort B)
- Cohort A only: Has received at least 2 lines of systemic therapy (endocrine or chemotherapy) in the palliative setting. Chemotherapy in an adjuvant setting for which patients relapsed within 6 months of completion can be considered as line(s) of palliative therapy.
- Cohort B only: Any number of prior lines of palliative chemotherapy.
Exclusion
- 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.
- Symptomatic brain metastasis.
- History of significant neurological or mental disorder, including seizures or dementia.
- Unable to comply with study procedures
- Systemic treatment with a strong CYP3A4 inhibitor or storn CYP450 inducer within 14 days prior to treatment Day 1
- Phase Ib lead-in can recruit patients who fulfil critieria for either Cohort A or Cohort B AND all other inclusion/exclusion criteria
Key Trial Info
Start Date :
July 13 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 1 2026
Estimated Enrollment :
74 Patients enrolled
Trial Details
Trial ID
NCT04520269
Start Date
July 13 2020
End Date
July 1 2026
Last Update
September 25 2025
Active Locations (1)
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1
National University Hospital
Singapore, Singapore