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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05278975
Other study ID # RS-TS-101-01
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date March 31, 2022
Est. completion date April 1, 2025

Study information

Verified date January 2024
Source RS Oncology LLC
Contact George Naumov, PhD
Phone (617) 835-5633
Email MITOPE@rsoncology.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an open-label, non-randomized, multicenter, translational Phase 1/2 dose-escalation and expansion study designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RSO-021 after intrapleural (IP) administration in patients with malignant pleural effusion (MPE) (non-mesothelioma) and MPE from mesothelioma.


Description:

This is a Phase 1/2, open-label, multi-center study whose primary Phase 1 stage objective is to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of RSO-021 (thiostrepton), a naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class, in patients with MPE from any solid tumor, including mesothelioma. In the Phase 2 stage, once the RP2D has been identified, the antitumor activity of RSO-021 will be evaluated in four recruitment arms; (1) in patients with MPE (non-mesothelioma), (2) in patients with MPE (non-mesothelioma) in combination with paclitaxel, (3) in patients with MPE from mesothelioma after first-line SoC, and (4) in patients with MPE from mesothelioma who have a 'window of opportunity' for treatment prior to first-line systemic therapy.


Recruitment information / eligibility

Status Recruiting
Enrollment 186
Est. completion date April 1, 2025
Est. primary completion date April 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Male or female = 18 years old. 2. ECOG performance status 0-1. 3. Histological diagnosis of solid tumor/mesothelioma with MPE. Expansion Cohort 2: 1. only patients with breast cancer, ovarian cancer or non-small cell lung cancer. 2. patients for whom paclitaxel is a recommended SoC therapy. 3. no contraindications to paclitaxel. 4. Patients with a disease burden that is predominantly pleural, and a pleural space that is accessible. Expansion Cohorts 1 and 2: MPE (non-mesothelioma): patients must have received at least 1 prior standard of care treatment regimen for advanced, unresectable malignancy, with documented progression. Expansion Cohort 3: MPE mesothelioma: patients must have received at least 1 prior standard-of-care treatment regimen for advanced, unresectable malignancy, with documented progression and there is no approved life extending alternative available. Expansion Cohort 4: MPE mesothelioma 'window of opportunity': patients should be treatment naïve, have refused or not be immediately requiring of systemic therapy and should be patients for whom drainage is planned immediately while further treatment options are arranged. It must be documented for each patient that protocol participation will not affect their subsequent ability to access standard systemic first line therapy due to RSO-021 being a local therapy. 6. Resolution of all acute reversible toxic effects of prior therapy or surgical procedure to Grade =1 (except alopecia). 7. For dose escalation: Archival paraffin block, ideally from the patient's most recent biopsy, should be provided prior to the first dose of study therapy, if sufficient tissue is available. For dose expansion cohorts: fresh tumor biopsy must be obtained. 1. Patients enrolled in the mesothelioma expansion phase will be requested to undergo a tumor biopsy during the screening period and after the third dose. 2. Patients enrolled in the non-mesothelioma expansion phase will be requested to undergo a tumor biopsy during the screening period and after the third dose only if medically feasible. 8. Patients must have adequate organ function. Exclusion Criteria: 1. Last dose of prior anti-cancer therapies: 1. Systemic anti-cancer therapy within 3 weeks or 5 half-lives prior to study entry, whichever is shorter. 2. Thoracic radiation therapy or significant surgery within 3 weeks prior to study entry. Localized palliative radiotherapy for pain control in non-target lesions is allowed during the screening period. 3. Received an investigational product or been treated with an investigational device within 30 days prior to first drug administration or plans to participate in any other clinical trial while on this study. 2. Previous or concurrent malignancy that would prevent evaluation of the primary endpoint (e.g. R/R hematological malignancy). 3. Patients whose extent of tumor or loculations would render intrapleural administration incomplete and/or ineffective. 4. Known hypersensitivity to the active ingredient or any excipient contained in the drug formulation. 5. History or clinical evidence of any surgical or medical condition which the investigator and/or medical monitor judges as likely to interfere with the results of the study or pose an additional risk in participating, e.g., rapidly progressive or uncontrolled disease involving a major organ system-vascular, cardiac, pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic, renal, endocrine, or an immunodeficiency, or clinically significant active psychiatric or abuse disorders. 6. Active infection with human immunodeficiency virus (HIV) and CD4+ T-cell count < 350/µL. Patients not on established anti-retroviral therapy for at least four weeks prior to first dose of study drug and having a detectable HIV viral load. Testing is not required for eligibility. 7. Active infection with hepatitis B (surface antigen); or infection with hepatitis C in absence of sustained virologic response. Testing is not required for eligibility. 8. Pregnant or breast-feeding patients. 9. Patients with symptomatic or unstable CNS primary tumor or metastases and/or carcinomatous meningitis. Patients with documented treated CNS metastases stable off steroids may be enrolled at the discretion of the investigator. 10. Therapeutic oral anticoagulation for a thromboembolic event (prophylactic anticoagulation is allowed as long as patient can undergo catheter placement and biopsy). LMWH is allowed on condition that it is medically acceptable to interrupt LMWH therapy for all study procedures. 11. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms within 15 days or other immunosuppressive drugs within 3 weeks prior to start of the study. Inhaled and topical corticosteroids are permitted. Up to 10 mg/day prednisone or equivalent is permitted.

Study Design


Intervention

Drug:
RSO-021
A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

Locations

Country Name City State
United Kingdom South Mead North Bristol Hopsital Bristol
United Kingdom NHS Greater Glasgow & Clyde Glasgow
United Kingdom Leeds Teaching Hospital Leeds
United Kingdom Facility: HOPE Clinical Trials Facility, Leicester Royal Infirmary Leicester
United Kingdom Barts Health NHS Cancer Institute London
United Kingdom Guys and St Thomas NHS Foundation Trust London
United Kingdom The Royal Marsden London
United Kingdom The Christie NHS Manchester
United Kingdom Northumbria NorthTyne Side General Hospital North Shields
United Kingdom Oxford University Hospitals NHS Foundation Oxford

Sponsors (1)

Lead Sponsor Collaborator
RS Oncology LLC

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Dose-limiting Toxicity The incidence of DLTs during the DLT assessment period. First 21 days of treatment.
Primary Frequency and Severity of Adverse Events (AE) The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality. Screening to 90 days from last dose.
Primary Dose Finding Determination of the MTD and/or the RP2D. Screening to 90 days from last dose.
Secondary Pharmacokinetics of RSO-021 Maximum Plasma Concentration (Cmax) Day 1 of dosing through 21 days post last dose.
Secondary Pharmacokinetics of RSO-021 Area Under the Curve (AUC) Day 1 of dosing through 21 days post last dose.
Secondary Objective Response Rate (ORR) ORR according to RECIST v1.1. Day 1 of dosing through day 90 after the last dose.
Secondary Disease Control Rate (DCR) The percentage of subjects with a complete response, partial response, or stable disease for at least 2 consecutive tumor assessments. Day 1 of dosing through day 90 after the last dose.
Secondary Progression Free Survival (PFS) Time from the date of initiation of study therapy to the date measurement criteria are first met for PD or death from any cause, whichever occurs first. Day 1 of dosing through day 90 after the last dose.
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