A Safety and Pharmacokinetics Study of RC220 Combined With Doxorubicin in Adult Participants With Solid Tumours.
- Conditions
- Solid TumoursAdvanced Solid Tumours
- Interventions
- Registration Number
- NCT06815575
- Lead Sponsor
- Race Oncology Ltd
- Brief Summary
This is a multi-centre, two-part, open-label, phase 1, first in human study of multiple ascending doses of RC220 bisantrene formulation alone and in combination with fixed dose doxorubicin to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) in adult patients with advanced solid tumours where an anthracycline may be considered as a treatment option / or is indicated.
The study will consist of Part 1 - dose-escalation, to determine the maximum tolerated combination dose of RC220 with doxorubicin to be evaluated in Part 2 - dose-expansion cohort, in patients with solid tumours that are anthracycline treatment naïve and for whom treatment with doxorubicin is indicated. The objective of Part 2 will be to confirm the safety and tolerability and evaluate the preliminary cardioprotective and anti-tumour efficacy of the maximum tolerated combined dose (MTCD) of RC220 with doxorubicin.
- Detailed Description
This study is an open-label, Phase 1 dose escalation trial with expansion cohort to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary cardioprotective and antitumor activity of RC220 in combination with doxorubicin in patients with advanced solid tumours.
The study is divided into two parts: dose escalation (Part 1), and dose expansion (Part 2).
In Part 1(Dose Escalation), patients will be enrolled sequentially into escalating dose cohorts up to 5 planned dose cohorts. Each patient in a dose cohort will receive an intravenous (IV) infusion of RC220 on Day 1 of the lead-in 21-day cycle and continue to the combination cycle, where patients will receive IV RC220 followed by IV doxorubicin on Day 1 of a 21-day cycle . New patients will be enrolled in each dose escalation cohort based on safety observed during the first 21 days of RC220 and doxorubicin combination treatment Cycle 1 until the MTCD is defined based on the recommendations of the Safety Review Committee (SRC). Patients will continue to be treated beyond the first combination cycle observation period until disease progression, unacceptable toxicity, withdrawal of consent or defined end of study, whichever occurs first.
An interim analysis of the accumulated safety, PK, early efficacy and PD (as available) will be conducted to confirm the MTCD of RC220 in combination with fixed dose doxorubicin for further evaluation of the safety and tolerability, preliminary cardioprotective and anti-tumour efficacy in an exploratory dose expansion cohort of patients with solid tumours that are anthracycline treatment naïve and for whom treatment with doxorubicin is indicated.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 53
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1: Dose Escalation Doxorubicin (Adriamycin) Participants will receive increasing doses of RC220 on Day 1 of 21-day monotherapy cycle and in combination with the approved fixed dose of Doxorubicin on Day 1 of 21-day combination therapy cycle. Combination treatment repeats every 21-day cycle in the absence of disease progression or unacceptable toxicity. The aim is to determine safety, tolerability and maximum tolerated combination dosage level to evaluate in Part 2. Part 2: Dose Expansion Doxorubicin (Adriamycin) Participants will receive the tolerated and appropriate combination dosage of RC220 with doxorubicin on day 1 of the 21-day cycle and treatment repeats in the absence of disease progression or unacceptable toxicity. The aim is to provide additional safety and tolerability and potential benefits of the combined dosage. Part 1: Dose Escalation RC220 Participants will receive increasing doses of RC220 on Day 1 of 21-day monotherapy cycle and in combination with the approved fixed dose of Doxorubicin on Day 1 of 21-day combination therapy cycle. Combination treatment repeats every 21-day cycle in the absence of disease progression or unacceptable toxicity. The aim is to determine safety, tolerability and maximum tolerated combination dosage level to evaluate in Part 2. Part 2: Dose Expansion RC220 Participants will receive the tolerated and appropriate combination dosage of RC220 with doxorubicin on day 1 of the 21-day cycle and treatment repeats in the absence of disease progression or unacceptable toxicity. The aim is to provide additional safety and tolerability and potential benefits of the combined dosage.
- Primary Outcome Measures
Name Time Method Part 1. Incidence of dose limiting toxicities (DLTs) During the first cycle of RC220 and doxorubicin treatment (1-21 days) Evaluated at each dose level RC220 combined with doxorubicin, as graded by National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0.
Part 1 and Part 2. Treatment emergent adverse events (TEAE) and serious adverse events (SAEs), First dose up to 30 days post last combination dose (up to 12 months) This includes clinically significant changes in vital signs, physical examination, electrocardiogram, echocardiogram and clinical laboratory tests, as graded by NCI CTCAE v5.0.
- Secondary Outcome Measures
Name Time Method Part 1. Best Overall Response (BOR) Up to 12 months Percentage of patients with best confirmed overall response of clinical response (CR) or partial response (PR) (evaluated by the investigator according to RECISTv1.1) until the time of disease progression.
Part 1. Duration of Response (DOR) Up to 12 months Defined as the time from the earliest date documented (CR or PR) (evaluated by the investigator according to RECISTv1.1) until disease progression or death (by any cause, in the absence of progression).
Part 1. Progression Free Survival (PFS) Up to 12 months Defined as the time of first treatment until disease progression or death (by any cause, in the absence of progression).
Part 2. Change from baseline in cardiac blood biomarker levels (hs-troponins and NT-proBNP), as measured by laboratory tests up to 12 months Part 2. Change from baseline in 2D-echocardiogram measurements including GLS, LV volume, LV mass, transmitral flow, atrial volumes. Up to 12 months 2D-echocardiograms are performed at specified timepoints. Each time a 2D-echocardiogram is performed, multiple measures will be collected, aggregated and reported on once by a single observer.
Measures collected from each 2D-echocardiogram, and compared to baseline, include:
* global longitudinal strain
* left ventricular mass
* left ventricular volumes
* transmitral flow
* left atrial volumePart 2. Change from baseline in cardiac magnetic resonance imaging (cMRI) cardiac function parameters (blood flow, global ventricular function, myocardial perfusion) Up to 12 months Each time a cMRI is performed, cMRI images are collected, assessed, compared and reported on in an aggregated manner by an independent cardiologist for changes in cardiac function measures (blood flow, global ventricular function, myocardial perfusion).
Part 2. Change from baseline in functional volume of peak oxygen uptake (VO2 peak). Defined as the highest amount of oxygen consumed at peak exercise. Up to 12 months Part 1. Maximum tolerated combined dose (MTCD) After the first dose of RC220 and doxorubicin treatment cycle (1-21 days) The MTCD is based on the incidence of Dose Limiting Toxicities (DLTs).
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Trial Locations
- Locations (3)
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Cancer Care Foundation
🇦🇺Miranda, New South Wales, Australia
Wyong Hospital
🇦🇺Wyong, New South Wales, Australia
Gosford Hospital🇦🇺Gosford, New South Wales, AustraliaMaree JarrettContact02 4320 3406maree.jarrett@health.nsw.gov.auDr. Craig KukardContact