A Safety and Pharmacokinetics Study of RC220 Combined With Doxorubicin in Adult Participants With Solid Tumours.

NCT06815575 | Recruiting Phase 1

• 1 other identifier: RAC-010
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 5

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.

Conditions

Solid Tumours; Advanced Solid Tumours

Keywords

Solid Tumours; Advanced Solid Tumours; Phase 1

Outcome Measures

Primary Outcomes (2)

• Part 1. Incidence of dose limiting toxicities (DLTs)

  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.

  During the first cycle of RC220 and doxorubicin treatment (1-21 days)

• Part 1 and Part 2. Treatment emergent adverse events (TEAE) and serious adverse events (SAEs),

  This includes clinically significant changes in vital signs, physical examination, electrocardiogram, echocardiogram and clinical laboratory tests, as graded by NCI CTCAE v5.0.

  First dose up to 30 days post last combination dose (up to 12 months)

Secondary Outcomes (8)

• Part 1. Maximum tolerated combined dose (MTCD)

  After the first dose of RC220 and doxorubicin treatment cycle (1-21 days)

• Part 1. Best Overall Response (BOR)

  Up to 12 months

• Part 1. Duration of Response (DOR)

  Up to 12 months

• Part 1. Progression Free Survival (PFS)

  Up to 12 months

• Part 2. Change from baseline in cardiac blood biomarker levels (hs-troponins and NT-proBNP), as measured by laboratory tests

  up to 12 months

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

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.

Drug: RC220; Drug: Doxorubicin (Adriamycin)

Part 2: Dose Expansion

EXPERIMENTAL

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.

Drug: RC220; Drug: Doxorubicin (Adriamycin)

Interventions

RC220 DRUG

Administered by intravenous infusion over 60 minutes.

Part 1: Dose Escalation; Part 2: Dose Expansion

Doxorubicin (Adriamycin) DRUG

60 mg/m2 administered by intravenous infusion over 10 minutes following adminstration of intravenous RC220 on Day 1 of the combination cycles.

Also known as: Doxorubicin Hydrochloride, Adriamycin®

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Able to give voluntary informed consent and understand the study and are willing to follow and complete all the study required procedures.
• Aged ≥ 18 years at the time of informed consent.
• Life expectancy ≥ 3 months.
• Have measurable or evaluable disease per RECIST v1.1. The target lesions must not have prior radiation or other locally treated area unless imaging-based progression has been clearly documented following radiation or other local therapy.
• Adequate haematological, liver, and kidney function as follows:
• Bone marrow reserve:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L without growth factor support in the 2 weeks prior to study entry.
• Haemoglobin ≥ 90 g/L without transfusion and/or without growth factor support in 2 weeks prior to study entry.
• Platelet count ≥ 100 × 109/L without transfusion in 2 weeks prior to study entry.
• Hepatic function:
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 3 × upper limit of normal (ULN) (≤5 × ULN if liver metastases or hepatic cell carcinoma (HCC)).
• Renal function:
• Serum creatinine \< 1.5 × ULN or Serum creatinine clearance (CrCL) \> 50 mL/min, as per the Cockcroft-Gault Equation Glomerular Filtration Rate: \[(140-age in years) × weight in kg\] / (7.2 × serum creatinine in mg/dL) (× 0.85 for females).
• In PART 2 only: Out of range values for 5a, b and c are allowable based on the discretion of the Investigator and with approval from Sponsor Medical Monitor.
• International normalized ratio (INR) /prothrombin time (PT) \< 2 x ULN, activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.

You may not qualify if:

• Females who are pregnant or nursing.
• Received cancer-directed therapy within the following timeframes:
• Antitumour therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy or investigational agent) within 28 days prior to the first dose of study treatment (or 5 times the half-life if shorter than 28 days, there can be exceptions on a case-by-case as approved by Sponsor Medical Monitor based on pharmacology). Note: concurrent use of hormone deprivation therapy for hormone-refractory prostate cancer, bisphosphonate or denosumab for skeletal related events per institution guideline is permitted.
• Wide-field radiation therapy within 28 days (or palliative radiation therapy within 7 days) prior to the first dose of study treatment or has not recovered from the side effects of radiation therapy in the opinion of the Investigator.
• Any other concurrent investigational device(s) or conventional agent(s) within 28 days (unless 5 times the half-life is shorter than 28 days) prior to the first dose of study treatment.
• Therapeutic radiopharmaceuticals must be stopped 8 weeks prior to the first dose of the study drug.
• Persisting Grade 2 or higher severity AEs from prior antitumour treatment as per CTCAE v5.0. Patients with pre-existing non-treatable Grade 2 toxicities may be eligible per discretion of the Investigator and with approval from Sponsor Medical Monitor (e.g., Grade 2 chemotherapy induced neuropathy).
• Patients with primary central nervous system (CNS) malignancy, symptomatic CNS metastases, meningeal metastases or leptomeningeal disease are not allowed.
• Note: Patients with asymptomatic CNS metastases are eligible if clinically controlled, which is defined as 1) ≥ 4 weeks of stable neurologic function following CNS-directed therapy prior to the first dose of study treatment 2) no evidence of CNS disease progression as determined by radiographic imaging ≥ 4 weeks prior to the first dose of study treatment, 3) ≥ 2 weeks from discontinuation of anti-seizure and steroid therapies (receiving prednisone ≤ 10 mg or equivalent steroid therapies is allowed) prior to the first dose of study treatment.
• Had major surgery within 28-days of the Screening Visit. Note: Patients who have undergone a non-major surgical procedure within 28-days prior to Screening must have recovered adequately from the surgery before the administration of the first dose of study drug. Exception: no waiting period applies following central venous catheter placement.
• History of tissue or organ transplantation.
• Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Exceptions: Daily prednisone equivalent ≤10 mg/day; topical, inhaled, or intranasal corticosteroids.
• History of severe infection deemed clinically significant by the Investigator or designee within 4 weeks or signs and symptoms of any active infection within 2 weeks prior to the first dose of study treatment.
• Active hepatitis B or C. Note: Hepatitis B virus (HBV) carriers without active disease (HBV DNA titer \< 1000 copies/mL or 200 IU/mL) or cured hepatitis C (negative HCV RNA test) with confirmed viral clearance that are not receiving ongoing treatment and without residual chronic liver disease may be enrolled.
• Confirmed human immunodeficiency virus (HIV) infection and receiving anti-retroviral therapy (ART). Patients with well controlled HIV infection (i.e., CD4+ count \>350 cells/μL and viral copies less than 400/mL after at least 4 weeks of ART) may be eligible per discretion of the Investigator and with approval from Sponsor Medical Monitor.

Sponsors & Collaborators

• Race Oncology Ltd: lead

Study Sites (5)

Gosford Hospital

Gosford, New South Wales, 2250, Australia

RECRUITING

Cancer Care Foundation

Miranda, New South Wales, 2228, Australia

RECRUITING

Wyong Hospital

Wyong, New South Wales, 2259, Australia

RECRUITING

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

RECRUITING

Prince of Wales Hospital

Shatin, Hong Kong

RECRUITING

MeSH Terms

Interventions

Doxorubicin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Marinella Messina

  Race Oncology Ltd

  STUDY DIRECTOR

Central Study Contacts

Michelle Huh

CONTACT

+61 414 771 687; michelle.huh@raceoncology.com

Study Design

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

Model Details: The Part 1 dose escalation part of the study will enrol up to 33 patients, guided by the Bayesian Optimal Interval (BOIN) design. Patients will be enrolled in cohorts of 3 for each of the 5 planned dose level cohorts. The Part 2 exploratory dose expansion part will enrol a single cohort of approximately 20 patients with solid tumours who have not previously been treated with an anthracycline. Patients will be treated at the MTCD of RC220 and doxorubicin as identified in Part 1. The sample size and patient population cohort will be confirmed following the interim analysis of safety, and PK data after the last patient in Part 1 completes the dose limiting toxicity (DLT) period.

Study Record Dates

• First Submitted: January 20, 2025
• First Posted: February 7, 2025
• Study Start: April 2, 2025
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): January 31, 2029
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

HK (2); AU (3)