A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

A Phase 1b/2a Multicenter Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

This is a Phase 1b/Phase 2a, open-label, multicenter study to determine the safety, tolerability, recommended Phase 2 dose (RP2D), efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) properties of idronoxil when rectally administered as a suppository (NOX66) to patients with any solid tumor (Part 1) and patients with metastatic castration-resistant prostate cancer (mCRPC), breast cancer (BC) and non-small-cell lung cancer (NSCLC) (Part 2) who are eligible for low-dose external beam radiotherapy (EBRT) for at least one symptomatic or minimally symptomatic lesion (for the prevention of symptoms).

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors
• Intervention / Treatment: Drug: NOX66; Drug: NOX66; Drug: NOX66; Drug: NOX66; Drug: NOX66; Radiation: EBRT

Detailed Description

The study is divided into 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). The study design allows an exploration of different doses of NOX66 (800 mg, 1200 mg, 1600 mg and 2400 mg) with safety monitoring to ensure the safety of the patients. In Cycle 1, NOX66 will be administered for 14 days followed by a 7-day rest period on a 21-day cycle. From Cycle 2 onwards, NOX66 will be administered for 7 days followed by a 7-day rest period on a 14-day cycle. Patients will continue to receive NOX66 on a cyclical basis until disease progression, unacceptable toxicity, withdrawal of consent, start of a new anticancer therapy, withdrawal of the patient by the Investigator or the end of study is reached.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas - MD Anderson Cancer Center - Genitourinary (GU) Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient has a minimum life expectancy of 6 months
• Histological or cytological confirmation of prostate cancer, BC, NSCLC and any other solid tumors
• Confirmed metastatic disease by imaging
• Documented disease progression following first or later lines of anticancer systemic treatment
• Patient is eligible for low-dose EBRT for at least one lesion
• Patients with prior RT are eligible, only if there is no potential for field overlap between the prior RT and the planned RT
• For patients with BC or NSCLC: Patient must have at least one measurable lesion as per RECIST v1.1 (in Part 2 only)
• Patient has ECOG performance status of 0 to 2
• Adequate bone marrow, renal, and liver function
• Metastatic Castration-resistant Prostate Cancer: Baseline testosterone levels ≤ 14.4 ng/dL and ongoing medical castration must be maintained throughout the duration of the study; patient has evidence of symptomatic and/or progressive disease
• Breast Cancer Patients: Known hormone receptor status (estrogen receptors/progesterone receptors or estrogen receptors alone). Breast cancer patients are allowed to be on background hormonal treatment.

Exclusion Criteria:

• Patient has tumor involvement of the central nervous system
• Impaired cardiac functioning or clinically significant cardiac disease
• Uncontrolled hypertension despite two concomitant antihypertensive therapies
• 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 or difficulties in absorption
• Patients with fecal impaction or uncontrolled irritable bowel disease
• Patients with inflammatory bowel disease
• Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the Investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent
• Patients with oligometastatic disease (fewer than 5 metastatic lesions) amenable to standard therapy will be excluded
• Patients who have had RT to the region of the rectum or will require RT to the region of the rectum during the trial
• Uncontrolled active infection requiring intravenous antibiotic, antiviral or anti-fungal medications within 14 days before the first dose administration
• Receiving or having received anticancer treatment
• Patient has received corticosteroids at a dose of > 10 mg prednisone/day or equivalent for any reason within 4 weeks prior to receiving the first dose administration
• Patient is not willing to use suppositories
• Patient has a positive reverse transcription polymerase chain reaction (RT-PCR) test for severe acute respiratory coronavirus 2 (SARS-CoV-2) prior to Screening or enrollment, or has clinical signs and symptoms consistent with SARS-CoV-2 infection; e.g., fever, dry cough, dyspnea, sore throat, fatigue or positive SARS-CoV-2 test result within 2 weeks prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Cohort 1: NOX66 800 mg	Drug: NOX66; NOX66 800 mg daily (400 mg suppository twice daily [BID]).; Drug: NOX66; NOX66 1200 mg daily (600 mg suppository BID).; Drug: NOX66; NOX66 1600 mg daily (800 mg suppository BID).; Drug: NOX66; NOX66 2400 mg daily (1200 mg suppository BID).; Drug: NOX66; NOX66 RP2D; Radiation: EBRT; The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.
Experimental: Part 1: Dose Cohort 2: NOX66 1200 mg	Drug: NOX66; NOX66 800 mg daily (400 mg suppository twice daily [BID]).; Drug: NOX66; NOX66 1200 mg daily (600 mg suppository BID).; Drug: NOX66; NOX66 1600 mg daily (800 mg suppository BID).; Drug: NOX66; NOX66 2400 mg daily (1200 mg suppository BID).; Drug: NOX66; NOX66 RP2D; Radiation: EBRT; The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.
Experimental: Part 1: Dose Cohort 3: NOX66 1600 mg	Drug: NOX66; NOX66 800 mg daily (400 mg suppository twice daily [BID]).; Drug: NOX66; NOX66 1200 mg daily (600 mg suppository BID).; Drug: NOX66; NOX66 1600 mg daily (800 mg suppository BID).; Drug: NOX66; NOX66 2400 mg daily (1200 mg suppository BID).; Drug: NOX66; NOX66 RP2D; Radiation: EBRT; The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.
Experimental: Part 1: Dose Cohort 4: NOX66 2400 mg	Drug: NOX66; NOX66 800 mg daily (400 mg suppository twice daily [BID]).; Drug: NOX66; NOX66 1200 mg daily (600 mg suppository BID).; Drug: NOX66; NOX66 1600 mg daily (800 mg suppository BID).; Drug: NOX66; NOX66 2400 mg daily (1200 mg suppository BID).; Drug: NOX66; NOX66 RP2D; Radiation: EBRT; The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.
Experimental: Part 2: Arm 1: Patients with mCRPC (RP2D NOX66)	Drug: NOX66; NOX66 800 mg daily (400 mg suppository twice daily [BID]).; Drug: NOX66; NOX66 1200 mg daily (600 mg suppository BID).; Drug: NOX66; NOX66 1600 mg daily (800 mg suppository BID).; Drug: NOX66; NOX66 2400 mg daily (1200 mg suppository BID).; Drug: NOX66; NOX66 RP2D; Radiation: EBRT; The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.
Experimental: Part 2: Arm 2: Patients with BC or NSCLC (RP2D NOX66)	Drug: NOX66; NOX66 800 mg daily (400 mg suppository twice daily [BID]).; Drug: NOX66; NOX66 1200 mg daily (600 mg suppository BID).; Drug: NOX66; NOX66 1600 mg daily (800 mg suppository BID).; Drug: NOX66; NOX66 2400 mg daily (1200 mg suppository BID).; Drug: NOX66; NOX66 RP2D; Radiation: EBRT; The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 (Dose Escalation): Number of Dose-limiting Toxicities (DLTs)	Maximum tolerated dose (MTD) and RP2D of NOX66 in combination with low-dose EBRT in patients with any solid tumor. MTD is defined as the dose level at which no more than 1 patient out of 6 has a DLT at the end of Cycle 1. RP2D is the highest dose at which no more than 1 patient out of 6 has a DLT at the end of Cycle 1 and the dosage form, is acceptable to patients. A DLT is defined as an AE that occurs during Cycle 1 (Day 1 to Day 21) that is unrelated to the disease, intercurrent illness or concomitant medications and that, possibly- definitely related to NOX66 alone or in combination with EBRT: Grade (G) ≥3 non-hematological toxicity; G≥3 febrile neutropenia; G4 thrombocytopenia > 5 days; G3 thrombocytopenia with bleeding or in combination with a G ≥3 blood and lymphatic system disorder.; G3 AST or ALT that is + a ≥G2 rise in bilirubin >7 days; AST or ALT > 8 × ULN; AE causing treatment delay > 14 days.	Cycle 1 (Day 1 to Day 21)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Incidence of Adverse Events (AEs) for NOX66	Characterization of the safety and tolerability of NOX66.	From Screening (Days -28 to -2) until the Follow-up visit/End of Study (EOS) (through study completion, an average of 19 month)
Part 1: TEAEs by Relationship to EBRT Administration	Evaluation of the safety and tolerability of both doses of EBRT (8 Gy or 20/25 Gy).	From Screening (Days -28 to -2) until the Follow-up visit/EOS (through study completion, an average of 19 month)

Collaborators and Investigators

• Sponsor: Noxopharm Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Actual): May 10, 2023
• Study Completion (Actual): June 7, 2023

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Maximum tolerated dose; Prostate-specific antigen; Dose Escalation; Dose Expansion; Recommended Phase 2 dose
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: NOX66-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No