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

Noxopharm

Status and phase: Terminated; Phase 1

Conditions: Metastatic Soft-tissue Sarcoma

Treatments: Drug: Doxorubicin; Drug: NOX66

Study type: Interventional

Funder types: Industry

Identifiers

NCT05100628

NOX66-004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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9 participants in 4 patient groups

Dose-Escalation Cohort 1: NOX66 800 mg + Doxorubicin

Experimental group

Treatment:

Drug: NOX66

Drug: NOX66

Drug: NOX66

Drug: Doxorubicin

Drug: NOX66

Dose-Escalation Cohort 2: NOX66 1200 mg + Doxorubicin

Experimental group

Treatment:

Drug: NOX66

Drug: NOX66

Drug: NOX66

Drug: Doxorubicin

Drug: NOX66

Dose-Escalation Cohort 3: NOX66 1800 mg + Doxorubicin

Experimental group

Treatment:

Drug: NOX66

Drug: NOX66

Drug: NOX66

Drug: Doxorubicin

Drug: NOX66

Dose-Expansion Cohort: NOX66 + Doxorubicin

Experimental group

Treatment:

Drug: NOX66

Drug: NOX66

Drug: NOX66

Drug: Doxorubicin

Drug: NOX66