Study of RSO-021 in Patients With Malignant Pleural Effusion Due to Advanced/Metastatic Solid Tumors Including Mesothelioma
Study Details
Study Description
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 |
|---|---|---|
| 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 two expansion cohorts in patients with MPE due to 1) non-mesothelioma solid tumors and 2) mesothelioma only tumors.
Study Design
Arms and Interventions
| 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 Names:
|
| Experimental: Phase 2 - 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 Names:
|
| Experimental: Phase 2 - 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Dose-limiting Toxicity [First 21 days of treatment.]
The incidence of DLTs during the DLT assessment period.
- Frequency and Severity of Adverse Events (AE) [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.
- Dose Finding [Screening to 90 days from last dose.]
Determination of the MTD and/or the RP2D.
Secondary Outcome Measures
- Pharmacokinetics of RSO-021 [Day 1 of dosing through 21 days post last dose.]
Maximum Plasma Concentration (Cmax)
- Pharmacokinetics of RSO-021 [Day 1 of dosing through 21 days post last dose.]
Area Under the Curve (AUC)
- Objective Response Rate (ORR) [Day 1 of dosing through day 90 after the last dose.]
ORR according to RECIST v1.1.
- Disease Control Rate (DCR) [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.
- Progression Free Survival (PFS) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female ≥ 18 years old.
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ECOG performance status 0-1.
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Dose escalation: histological diagnosis of MPE from any solid tumor, including mesothelioma.
Dose expansions: histological diagnosis of MPE caused by non-mesothelioma solid tumor or mesothelioma.
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For patients with MPE from any other solid tumors, the MPE must be considered the priority for symptom control as potentially life limiting (or quality of life limiting).
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MPE other solid tumors: patients must have received at least 1 prior standard of care treatment regimen for advanced, unresectable malignancy, with documented progression per RECIST 1.1.
MPE mesothelioma: patients must have received at least 1 prior standard of care treatment regimen for advanced, unresectable malignancy, with documented progression (revised mRECIST 1.1 for mesothelioma) and there is no approved life extending alternative available.
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Resolution of all acute reversible toxic effects of prior therapy or surgical procedure to Grade ≤1 (except alopecia).
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For dose escalation cohorts: tumor tissue (a minimum of 10 and up to 15 unstained slides), or 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: fresh tumor biopsy will be obtained.
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Patients enrolled in the mesothelioma expansion stage will be requested to undergo a tumor biopsy during the screening period and after the third dose.
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Patients enrolled in the non-mesothelioma expansion stage will be requested to undergo a tumor biopsy during the screening period and after the third dose only if medically feasible.
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Patients must have adequate organ function.
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If not postmenopausal or surgically sterile, patients must be willing to practice at least one of the following highly effective methods of birth control (defined as having a low failure rate, i.e., less than 1% per year) for at least a (partner's) menstrual cycle before and for 4 months after last study drug administration:
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True abstinence, when this is in line with the preferred and usual lifestyle of the patient, from sexual intercourse with a member of the opposite sex;
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Sexual intercourse with vasectomized male/sterilized female partner;
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Hormonal female contraceptive (oral, parenteral, intravaginal, implantable or transdermal) for at least 3 consecutive months prior to investigational product administration (when not clinically contraindicated as in breast, ovarian and endometrial cancers);
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Use of an intrauterine contraceptive device.
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Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion Criteria:
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Last dose of prior anti-cancer therapies:
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Systemic anti-cancer therapy within 3 weeks or 5 half-lives prior to study entry, whichever is shorter.
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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.
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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.
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Previous or concurrent malignancy that would prevent evaluation of the primary endpoint (e.g. R/R hematological malignancy).
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Patients whose extent of tumor or loculations would render intrapleural administration incomplete and/or ineffective.
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Known hypersensitivity to the active ingredient or any excipient contained in the drug formulation.
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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.
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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.
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Active infection with hepatitis B (surface antigen); or infection with hepatitis C in absence of sustained virologic response. Testing is not required for eligibility.
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Pregnant or breast-feeding patients.
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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.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Facility: HOPE Clinical Trials Facility, Leicester Royal Infirmary | Leicester | United Kingdom | LE1 5WW |
Sponsors and Collaborators
- RS Oncology LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RS-TS-101-01