Phase I, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM534 Administered Intravenously to Patients With Advanced Solid Tumors

PharmaMar3 sites in 1 country30 target enrollmentDecember 23, 2022

ConditionsPatients With Advanced Solid Tumors

InterventionsPM534

DrugsPM534

Overview

Phase: Phase 1
Intervention: PM534
Conditions: Patients With Advanced Solid Tumors
Sponsor: PharmaMar
Enrollment: 30
Locations: 3
Primary Endpoint: Determination of the Maximum Tolerated Dose and the Recommended Dose
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goals of this trial are to identify the dose limiting toxicities, to determine the maximum tolerated dose and the recommended dose of PM534 in patients with advanced solid tumors. All Patients will receive PM534 via intravenous.

Detailed Description

This is a prospective, open-label, dose-escalating phase I study in patients with advanced solid tumors. Patients will be included in cohorts of a minimum of three or six patients to receive PM534 at successively increasing dose levels.

Registry

clinicaltrials.gov

Start Date

December 23, 2022

End Date

October 1, 2026

Last Updated

8 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

PharmaMar

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Voluntarily signed and dated written informed consent, obtained prior to any specific study procedure.
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
•Patients must have:
•3.1 Pathologically confirmed diagnosis of advanced solid tumors 3.2 No more than three prior chemotherapy lines.
•Patients with measurable or non-measurable disease according to the RECIST v.1.
•Recovery to grade ≤1 from drug-related adverse events (AEs) of previous disease treatments, excluding grade 2 alopecia.
•Laboratory values within seven days prior to first infusion:
•Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L, platelet count ≥100 x 10⁹/L and hemoglobin ≥9 g/dL
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x upper limit of normal (ULN).
•Total bilirubin ≤ULN (up to 1.5 x ULN for patients with Gilbert's syndrome).

Exclusion Criteria

•Concomitant diseases/conditions:
•Increased cardiac risk:
•History of long QT syndrome.
•Corrected QT interval (QTcF, Fridericia correction) ≥450 msec on screening electrocardiogram (ECG).
•History of or current ischemic heart disease, including myocardial infarction, stable/unstable angina, coronary arteriography or cardiac stress testing with findings consistent with coronary occlusion or infarction or symptomatic arrhythmia.
•History of heart failure or left ventricular dysfunction (left ventricular ejection fraction \[LVEF\] ≤50%) by multiple-gated acquisition scan (MUGA) or echocardiography (ECHO).
•Clinically significant ECG abnormalities, including any of the following: right bundle branch block with left anterior hemiblock, second (Mobitz II) or third degree atrioventricular block and findings suggestive of ischemic heart disease.
•Symptomatic arrhythmia.
•Use of a cardiac pacemaker.
•History of or current peripheral vascular disease or cerebrovascular disease.

Arms & Interventions

PM534

Patients will be included in cohorts of a minimum of three or six patients to receive PM534 at successively increasing dose levels.

Intervention: PM534

Outcomes

Primary Outcomes

Determination of the Maximum Tolerated Dose and the Recommended Dose

Time Frame: From the date of first infusion of PM534 to the date of study termination, up to 46 months

A fully evaluable patient is a patient evaluable for the primary objective (i.e., determination of the MTD and the RD).

Secondary Outcomes

Safety AEs of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety Hb of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety neutrophils of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety platelets of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety BT of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety ALT/AST of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety ALK of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
Safety creatinine of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)
QT Assessment(During Day of Cycle 1 (each cycle lasts 21 days))
Pharmacokinetics Cmax of PM534(Cycle 1 from all patients, and also in Cycle 2 from treated patients once the MTD has been determined(each cycle is 21 days).)
Pharmacokinetics AUC of PM534(Cycle 1 from all patients, and also in Cycle 2 from treated patients once the MTD has been determined(each cycle is 21 days).)
Pharmacogenomics Plasma AUC(0-t) of PM534(Cycle 1 from all patients, and also in Cycle 2 from patients treated once the MTD has been determined) (each cycle is 21 days))
Pharmacogenomics Plasma Cmax of PM534(Cycle 1 from all patients, and also in Cycle 2 from patients treated once the MTD has been determined) (each cycle is 21 days))
Pharmacogenomics Plasma half life of PM534(Cycle 1 from all patients, and also in Cycle 2 from patients treated once the MTD has been determined) (each cycle is 21 days))
Pharmacogenomics Total body plasma clearance of PM534(Cycle 1 from all patients, and also in Cycle 2 from patients treated once the MTD has been determined) (each cycle is 21 days))
Pharmacogenomics Volume of distribution of PM534(Cycle 1 from all patients, and also in Cycle 2 from patients treated once the MTD has been determined) (each cycle is 21 days))
Pharmacogenomics Percentage of dose recovered in urine of PM534(Cycle 1 from all patients, and also in Cycle 2 from patients treated once the MTD has been determined) (each cycle is 21 days))
Efficacy of PM534(From the date of first infusion of PM534 to the date of study termination, up to 46 months)