This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05278975
Recruitment Status : Recruiting
First Posted : March 15, 2022
Last Update Posted : January 26, 2024
Sponsor:
Information provided by (Responsible Party):
RS Oncology LLC

Brief 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.

Condition or disease Intervention/treatment Phase
Malignant Pleural Effusion Malignant Pleural Mesothelioma Mesothelioma Mesotheliomas Pleural Mesothelioma; Lung Pleural Effusion, Malignant Drug: RSO-021 Phase 1 Phase 2

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 186 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Translational Phase 1/2 Dose-Escalation and Expansion Study to Determine Safety, Tolerability, and Recommended Phase 2 Dose of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including Mesothelioma
Actual Study Start Date : March 31, 2022
Estimated Primary Completion Date : April 1, 2025
Estimated Study Completion Date : April 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: Phase 1 - Dose Escalation
RSO-021 administered in increasing doses as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle.
Drug: RSO-021
A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.
Other Name: Thiostrepton

Experimental: Ph2 - Dose Expansion - MPE from non-mesothelioma solid tumors
RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with MPE from non-mesothelioma solid tumors.
Drug: RSO-021
A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.
Other Name: Thiostrepton

Experimental: Ph2 - Dose Expansion - MPE from mesothelioma
RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with MPE from mesothelioma.
Drug: RSO-021
A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.
Other Name: Thiostrepton

Experimental: P2 - Dose Expansion - mesothelioma -First line treatment prior to Ipi/Nivo
RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with mesothelioma. This local treatment with RSO-021 is prior to systemic treatment of Ipi/Nivo.
Drug: RSO-021
A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.
Other Name: Thiostrepton

Experimental: Ph2 - Dose Expansion - MPE from non-mesothelioma solid tumors combination with Paclitaxel
RSO-021 administered at the MTD/RP2D as a solution for pleural infusion through an indwelling IP catheter, administered as a single dose on Day 1 of each week of a 21-day treatment cycle in patients with MPE from non-mesothelioma solid tumors. In combination with Paclitaxel. Paclitaxel will be administered as a systemic therapy per SoC and the approved labeling based on the tumor type being treated. Paclitaxel is commercially available in the UK
Drug: RSO-021
A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.
Other Name: Thiostrepton




Primary Outcome Measures :
  1. Dose-limiting Toxicity [ Time Frame: First 21 days of treatment. ]
    The incidence of DLTs during the DLT assessment period.

  2. Frequency and Severity of Adverse Events (AE) [ Time Frame: Screening to 90 days from last dose. ]
    The incidences and percentages of patients experiencing AEs summarized by NCI CTCAE version 5.0 grade and by causality.

  3. Dose Finding [ Time Frame: Screening to 90 days from last dose. ]
    Determination of the MTD and/or the RP2D.


Secondary Outcome Measures :
  1. Pharmacokinetics of RSO-021 [ Time Frame: Day 1 of dosing through 21 days post last dose. ]
    Maximum Plasma Concentration (Cmax)

  2. Pharmacokinetics of RSO-021 [ Time Frame: Day 1 of dosing through 21 days post last dose. ]
    Area Under the Curve (AUC)

  3. Objective Response Rate (ORR) [ Time Frame: Day 1 of dosing through day 90 after the last dose. ]
    ORR according to RECIST v1.1.

  4. Disease Control Rate (DCR) [ Time Frame: Day 1 of dosing through day 90 after the last dose. ]
    The percentage of subjects with a complete response, partial response, or stable disease for at least 2 consecutive tumor assessments.

  5. Progression Free Survival (PFS) [ Time Frame: Day 1 of dosing through day 90 after the last dose. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05278975


Contacts
Layout table for location contacts
Contact: George Naumov, PhD (617) 835-5633 MITOPE@rsoncology.com

Locations
Layout table for location information
United Kingdom
South Mead North Bristol Hopsital Recruiting
Bristol, United Kingdom, BS105NB
Contact: Louise Standon       louise.stadon@nbt.nhs.uk   
Principal Investigator: Nick Maskell, MD         
NHS Greater Glasgow & Clyde Recruiting
Glasgow, United Kingdom
Contact: Stephanie Hughes       stephanie.hughes@ggc.scot.nhs.uk   
Principal Investigator: Kevin Blyth, MD         
Leeds Teaching Hospital Recruiting
Leeds, United Kingdom, LS970F
Contact       leedsth-tr.earlyphaseadmin@nhs.net   
Principal Investigator: Kevin Franks, MD         
Facility: HOPE Clinical Trials Facility, Leicester Royal Infirmary Recruiting
Leicester, United Kingdom, LE1 5WW
Contact: Molly Scotland       molly.scotland@uhl-tr.nhs.uk   
Principal Investigator: Dean Fennell, MD         
Barts Health NHS Cancer Institute Recruiting
London, United Kingdom, EC1A7BE
Contact: Maria Lapuente       m.lapuente@nhs.net   
Principal Investigator: Peter Szlosarek, MD         
Guys and St Thomas NHS Foundation Trust Recruiting
London, United Kingdom, SE19RT
Contact: George Borley       earlyphaseresearchteam@gstt.nhs.uk   
Principal Investigator: James Spicer, MD         
The Royal Marsden Recruiting
London, United Kingdom, SW3 6JJ
Contact: Bianca Peet       Bianca.Peet@rmh.nhs.uk   
Principal Investigator: Sanjay Popat, MD         
The Christie NHS Recruiting
Manchester, United Kingdom, M204BX
Contact: Amy Henshaw       amy.henshaw@nhs.net   
Principal Investigator: Fiona Thistlethwaite, MD         
Northumbria NorthTyne Side General Hospital Recruiting
North Shields, United Kingdom, NE29 8NH
Contact: Jessica Reynolds       jessica.reynolds@northumbria-healthcare.nhs.uk   
Principal Investigator: Avinash Aujayeb, MD         
Oxford University Hospitals NHS Foundation Recruiting
Oxford, United Kingdom, OX42PG
Contact: David Mukkath       trialadministrator4@oncology.ox.ac.uk   
Principal Investigator: Simon Lord, MD         
Sponsors and Collaborators
RS Oncology LLC
Investigators
Layout table for investigator information
Principal Investigator: James Spicer, MD Guys Hospital
Layout table for additonal information
Responsible Party: RS Oncology LLC
ClinicalTrials.gov Identifier: NCT05278975    
Other Study ID Numbers: RS-TS-101-01
First Posted: March 15, 2022    Key Record Dates
Last Update Posted: January 26, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Mesothelioma
Mesothelioma, Malignant
Pleural Effusion, Malignant
Pleural Effusion
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pleural Diseases
Thiostrepton
Anti-Bacterial Agents
Anti-Infective Agents