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

NCT ID: NCT05100628

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-11
• Study Completion Date: 2023-05-26

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.

Conditions

Metastatic Soft-tissue Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose-Escalation Cohort 1: NOX66 800 mg + Doxorubicin

Group Type: EXPERIMENTAL

NOX66

Intervention Type: DRUG

NOX66 800 mg (400 mg suppository twice daily [BID]).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be given at 75 mg/m\^2 as an intravenous infusion on Day 2 of the 21-day cycle for up to 6 cycles.

Dose-Escalation Cohort 2: NOX66 1200 mg + Doxorubicin

Group Type: EXPERIMENTAL

NOX66

Intervention Type: DRUG

NOX66 1200 mg daily (600 mg suppository BID).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be given at 75 mg/m\^2 as an intravenous infusion on Day 2 of the 21-day cycle for up to 6 cycles.

Dose-Escalation Cohort 3: NOX66 1800 mg + Doxorubicin

Group Type: EXPERIMENTAL

NOX66

Intervention Type: DRUG

NOX66 1800 mg daily (600 mg suppository thrice daily).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be given at 75 mg/m\^2 as an intravenous infusion on Day 2 of the 21-day cycle for up to 6 cycles.

Dose-Expansion Cohort: NOX66 + Doxorubicin

Group Type: EXPERIMENTAL

NOX66

Intervention Type: DRUG

MTD of the combination of NOX66 and doxorubicin will be determined in the dose-escalation cohort of the study. The selected dose will be administered in combination with Doxorubicin.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be given at 75 mg/m\^2 as an intravenous infusion on Day 2 of the 21-day cycle for up to 6 cycles.

Interventions

NOX66

NOX66 800 mg (400 mg suppository twice daily [BID]).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

Intervention Type: DRUG

NOX66

NOX66 1200 mg daily (600 mg suppository BID).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

Intervention Type: DRUG

NOX66

NOX66 1800 mg daily (600 mg suppository thrice daily).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

Intervention Type: DRUG

NOX66

MTD of the combination of NOX66 and doxorubicin will be determined in the dose-escalation cohort of the study. The selected dose will be administered in combination with Doxorubicin.

Intervention Type: DRUG

Doxorubicin

Doxorubicin will be given at 75 mg/m\^2 as an intravenous infusion on Day 2 of the 21-day cycle for up to 6 cycles.

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Noxopharm Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope

Duarte, California, United States

Mayo Clinic Florida - Oncology

Jacksonville, Florida, United States

Mayo Clinic

Rochester, Minnesota, United States

Site name Washington University School of Medicine in Saint Louis

St Louis, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NOX66-004

Identifier Type: -

Identifier Source: org_study_id