Clinical trial NCT05100628: A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma
Official title: A Dose Escalation and Dose Expansion Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma - CEP-2
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Soft-tissue Sarcoma
Keywords: Doxorubicin
Dose-escalation study
Dose-expansion study
Maximum tolerated dose
Lead sponsor: Noxopharm Limited
Sponsor class: INDUSTRY
First posted: 2021-10-29
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Dose Escalation: Number of Patients With Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 1 of each dose (Cycle length is 21 days)
measure: Number of Patients With Adverse Events (AEs) for NOX66
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida - Oncology
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Site name Washington University School of Medicine in Saint Louis
state: Missouri
Study officials:
References: