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

NCT ID: NCT05278975

Last Updated: 2024-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

186 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-31

Study Completion Date

2025-04-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Malignant Pleural Effusion Malignant Pleural Mesothelioma Mesothelioma Mesotheliomas Pleural Mesothelioma; Lung Pleural Effusion, Malignant

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

RSO-021

Intervention Type DRUG

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

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.

Group Type EXPERIMENTAL

RSO-021

Intervention Type DRUG

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

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.

Group Type EXPERIMENTAL

RSO-021

Intervention Type DRUG

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

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.

Group Type EXPERIMENTAL

RSO-021

Intervention Type DRUG

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

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

Group Type EXPERIMENTAL

RSO-021

Intervention Type DRUG

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

Interventions

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RSO-021

A naturally-occurring, sulfur-rich, cyclic oligopeptide antibiotic of the thiopeptide class.

Intervention Type DRUG

Other Intervention Names

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Thiostrepton

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RS Oncology LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Spicer, MD

Role: PRINCIPAL_INVESTIGATOR

Guys Hospital

Locations

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South Mead North Bristol Hopsital

Bristol, , United Kingdom

Site Status RECRUITING

NHS Greater Glasgow & Clyde

Glasgow, , United Kingdom

Site Status RECRUITING

Leeds Teaching Hospital

Leeds, , United Kingdom

Site Status RECRUITING

Facility: HOPE Clinical Trials Facility, Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status RECRUITING

Barts Health NHS Cancer Institute

London, , United Kingdom

Site Status RECRUITING

Guys and St Thomas NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

The Royal Marsden

London, , United Kingdom

Site Status RECRUITING

The Christie NHS

Manchester, , United Kingdom

Site Status RECRUITING

Northumbria NorthTyne Side General Hospital

North Shields, , United Kingdom

Site Status RECRUITING

Oxford University Hospitals NHS Foundation

Oxford, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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George Naumov, PhD

Role: CONTACT

(617) 835-5633

Facility Contacts

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Louise Standon

Role: primary

Stephanie Hughes

Role: primary

Role: primary

Molly Scotland

Role: primary

Maria Lapuente

Role: primary

George Borley

Role: primary

Bianca Peet

Role: primary

Amy Henshaw

Role: primary

Jessica Reynolds

Role: primary

David Mukkath

Role: primary

Other Identifiers

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RS-TS-101-01

Identifier Type: -

Identifier Source: org_study_id

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