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

NCT04957290 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: NOX66-005
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Keywords

Dose Escalation; Dose Expansion; Prostate-specific antigen; Maximum tolerated dose; Recommended Phase 2 dose

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Part 1: Incidence of Adverse Events (AEs) for 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

  From Screening (Days -28 to -2) until the Follow-up visit/EOS (through study completion, an average of 19 month)

Study Arms (6)

Part 1: Dose Cohort 1: NOX66 800 mg

EXPERIMENTAL

Drug: NOX66; Radiation: EBRT

Part 1: Dose Cohort 2: NOX66 1200 mg

EXPERIMENTAL

Drug: NOX66; Radiation: EBRT

Part 1: Dose Cohort 3: NOX66 1600 mg

EXPERIMENTAL

Drug: NOX66; Radiation: EBRT

Part 1: Dose Cohort 4: NOX66 2400 mg

EXPERIMENTAL

Drug: NOX66; Radiation: EBRT

Part 2: Arm 1: Patients with mCRPC (RP2D NOX66)

EXPERIMENTAL

Drug: NOX66; Radiation: EBRT

Part 2: Arm 2: Patients with BC or NSCLC (RP2D NOX66)

EXPERIMENTAL

Drug: NOX66; Radiation: EBRT

Interventions

NOX66 DRUG

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

Part 1: Dose Cohort 1: NOX66 800 mg

EBRT RADIATION

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.

Part 1: Dose Cohort 1: NOX66 800 mg; Part 1: Dose Cohort 2: NOX66 1200 mg; Part 1: Dose Cohort 3: NOX66 1600 mg; Part 1: Dose Cohort 4: NOX66 2400 mg; Part 2: Arm 1: Patients with mCRPC (RP2D NOX66); Part 2: Arm 2: Patients with BC or NSCLC (RP2D NOX66)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Noxopharm Limited: lead

Study Sites (2)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

The University of Texas - MD Anderson Cancer Center - Genitourinary (GU) Cancer Center

Houston, Texas, 77030, United States

Location

Limitations and Caveats

Dose escalation progressed through the first 3 planned dose levels before the Sponsor decided to terminate the study for business reasons; the decision was not based on any safety concerns with NOX66. Due to early termination, none of the efficacy parameters were able to be measured therefore only safety outcomes are available.

Results Point of Contact

• Title: Lorena, Director Clinical Operations
• Organization: Noxopharm

lorena.figueroa@noxopharm.com

+ 61 2 9144 2223

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: July 12, 2021
• Study Start: October 25, 2021
• Primary Completion: May 10, 2023
• Study Completion: June 7, 2023
• Last Updated: June 18, 2024
• Results First Posted: June 18, 2024

Record last verified: 2024-05

Locations

US (2)