A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma

Phase 1

Terminated

• Conditions: Metastatic Soft-tissue Sarcoma
• Interventions: Drug: NOX66; Drug: Doxorubicin

• Registration Number: NCT05100628
• Lead Sponsor: Noxopharm Limited

Brief Summary

This is a Phase I, open-label, dose-escalation and dose-expansion study of NOX66 given rectally, in cohorts of patients with metastatic soft tissue sarcoma (STS) who have not been exposed to anthracycline therapy, using a fixed dose-escalation schema every 21 days to establish the maximum tolerated dose (MTD) of the combination of NOX66 and doxorubicin.

Detailed Description

The study will contain dose-escalation cohorts and dose-expansion cohorts. The study design allows an exploration of different doses of NOX66 with safety monitoring to ensure the safety of the patients.

Dose-escalation cohorts: It will include three planned Treatment Groups (800, 1200, 1800 mg daily) and patients enrolled in these groups will receive 7 days of monotherapy treatment with NOX66 followed by a 5-day washout period. Thereafter, patients will enter a combination therapy (only if no significant toxicity is observed during monotherapy). This will commence with Cycle 1, which will consist of 7 days of NOX66, and on Day 2 of the 21-day cycle, doxorubicin will be administered. Patients will continue to be treated for up to 6 x 21-day cycles of NOX66 and doxorubicin. New patients will be entered at the next dose level of NOX66, if no dose-limiting toxicities have occurred among the first 3 patients at the end of cycle 1. During the dose-escalation, MTD of the combination of NOX66 and doxorubicin will be determined.

Dose-expansion cohort: On completion of the dose-escalation cohort, patients will be enrolled into a dose-expansion at the MTD of the combination of NOX66 and doxorubicin. All patients will enter directly into 21-day combination cycles and will be given NOX66 therapy for 7 days and doxorubicin will be administered on Day 2 of each cycle. Treatment will be terminated upon disease progression, unacceptable toxicity, or a maximum of 6 cycles.

Study Timeline

• Study First Submitted: 2021-10-20
• Study First Submitted QC: 2021-10-20
• Study First Posted: 2021-10-29
• Study Start: 2022-02-11
• Primary Completion: 2023-05-01
• Study Completion: 2023-05-26
• Results First Submitted: 2024-03-27
• Status Verified: 2024-11
• Results First Submitted QC: 2024-11-24
• Last Update Submitted: 2024-11-24
• Results First Posted: 2025-01-06
• Last Update Posted: 2025-01-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

• Adult patients with a histologically confirmed diagnosis of metastatic or recurrent soft tissue sarcoma
• Patients for whom treatment with doxorubicin is considered to be appropriate
• Left ventricular ejection fraction ≥ 50%
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Disease that is considered measurable according to RECIST v1.1.

Exclusion Criteria

• Histologically or cytologically confirmed Kaposi's sarcoma, gastrointestinal stromal tumor (GIST), extra-skeletal myxoid chondrosarcoma, epithelioid hemangioendothelioma, and desmoid tumor
• Untreated metastases to the central nervous system
• Received previous treatment with anthracyclines and anthracenediones
• Previous radiation therapy to the mediastinal or pericardial area
• A known allergy to any of the treatment components
• Patient not willing to use suppositories
• Patients with a colostomy
• Patients who have had a colectomy (total or left hemicolectomy) with re-anastomosis
• Patients for whom administration of the suppositories are likely to cause pain (e.g., inflamed hemorrhoids, fissures, or lesions of the anus or rectum)
• Patients with fecal impaction, chronic idiopathic constipation, or chronic diarrhea or alternating irritable bowel disease
• Patients with inflammatory bowel disease
• Previous treatment with an investigational agent or the non-approved use of a drug or device within 4 weeks before study entry
• Uncontrolled diabetes mellitus
• Patients who require concomitant use of strong inhibitors or inducers of CYP3A4, CYP2D6 or P- glycoprotein (P- gp)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose-Escalation Cohort 1: NOX66 800 mg + Doxorubicin	NOX66	-
Dose-Escalation Cohort 2: NOX66 1200 mg + Doxorubicin	NOX66	-
Dose-Escalation Cohort 3: NOX66 1800 mg + Doxorubicin	NOX66	-
Dose-Expansion Cohort: NOX66 + Doxorubicin	NOX66	-
Dose-Escalation Cohort 1: NOX66 800 mg + Doxorubicin	Doxorubicin	-
Dose-Escalation Cohort 2: NOX66 1200 mg + Doxorubicin	Doxorubicin	-
Dose-Escalation Cohort 3: NOX66 1800 mg + Doxorubicin	Doxorubicin	-
Dose-Expansion Cohort: NOX66 + Doxorubicin	Doxorubicin	-

Primary Outcome Measures

Name	Time	Method
Dose Escalation: Number of Patients With Dose-limiting Toxicities (DLTs)	Cycle 1 of each dose (Cycle length is 21 days)	Determination of the MTD of NOX66 in combination with doxorubicin. MTD is defined as the dose level at which no more than 1 patient out of 6 experiences a DLT at the end of Cycle 1.
Number of Patients With Adverse Events (AEs) for NOX66	From first study treatment with DOX66 monotherapy through study completion, approximately of 14 months and 20 days. From February 11, 2022, to May 1, 2023	Characterization of the safety and tolerability of NOX66.

Trial Locations

Locations (4)

Site name Washington University School of Medicine in Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

City of Hope; 🇺🇸 Duarte, California, United States

Mayo Clinic Florida - Oncology; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States