Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer

Phase 1

Completed

• Conditions: Cancer
• Interventions: Drug: NOX66; Radiation: Irradiation Therapy

• Registration Number: NCT03307629
• Lead Sponsor: Noxopharm Limited

Brief Summary

The study is intended as a Proof of Concept and dose confirmation study. The primary objective of this study is to observe safety and tolerability of idronoxil (NOX66) in combination with radiotherapy (at palliative doses) in patients with metastatic castrate-resistant prostate cancer (CRPC) and to confirm dose in order to progress to Phase 2/3.

Detailed Description

This study will investigate three escalating doses of NOX66 in combination with palliative dose of radiation therapy to establish safety profile and / or obtain efficacy signals and to determine the optimal dose for future radiation therapy combination studies.

The key hypotheses to be tested in this study are:

1. That NOX66 can be safely added to palliative dose radiation therapy.

2. That NOX66 may sensitise tumours to palliative doses of radiation therapy

3. That NOX66 in combination with radiation therapy may trigger or augment an abscopal effect

Participants will have a minimum of 1 symptomatic lesion amenable to radiation therapy.

Radiation therapy will be delivered at a 20Gy dosage over 5 fractions. NOX66 will be taken on 13 consecutive days starting 1 day prior to radiotherapy.

The response of irradiated and non-irradiated target tumour lesions will be measured by CT/MRI scan and RECIST1.1 criteria at three time points post treatment. Pain response will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF) instrument at five time points post treatment.

Patients will be suitable for the study as they become indicated for palliative radiation therapy for management of their cancer.

This study will enrol up to 24 patients in 3 NOX66 dose level cohorts of 4 patients (n=12) and an expansion cohort of 12 patients. Dose escalation decisions will be based on patients who experience adverse events directly related to NOX66 treatment.

Following the review of accumulated safety data, disease status and treatment efficacy signals at WEEK 6 for the first 12 patients, the Study Steering Committee will determine the dose at which to continue treatment for the expansion patient Cohort 4 in the study. A further 12 patients will be recruited at this dose level.

Study Timeline

• Study First Submitted: 2017-09-27
• Study First Submitted QC: 2017-10-05
• Study First Posted: 2017-10-12
• Study Start: 2017-11-01
• Primary Completion: 2019-12-01
• Study Completion: 2020-09-15
• Results First Submitted: 2024-03-27
• Status Verified: 2025-07
• Results First Submitted QC: 2025-07-27
• Last Update Submitted: 2025-07-27
• Results First Posted: 2025-07-29
• Last Update Posted: 2025-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 25

Inclusion Criteria

1. Provision of informed consent

2. ≥ 18 years of age

3. Histologically confirmed prostate cancer and/or PSA of >100 ng/mL at original diagnosis

4. Metastatic disease evidenced by either CT/MRI imaging or bone scan

5. Objective evidence of disease progression as defined by either:

   i. Radiographic progression of in nodal or visceral metastases and bone disease progression with 2 or more new lesions ii. Rising PSA value ≥2ng/ml in at least 3 measurements, at least 1 week apart, with castrate levels of serum testosterone.

6. Eligible to receive palliative radiation therapy for management of disease

7. At least one symptomatic lesion which is suitable for radiation therapy

8. ECOG Performance status 0-2

9. A minimum life expectancy of 24 weeks

10. Adequate bone marrow, hepatic and renal function as evidenced by:

    • Absolute neutrophil count (ANC) > 1.5 x 109/L
    • Platelet count > 100 x 109/L
    • Hemoglobin > 9.0 g/dL
    • Serum bilirubin < 1.5 x ULN
    • AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
    • Serum creatinine < 1.5 x ULN

11. Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist

12. At least 4 weeks must have elapsed prior to commencement of NOX66 treatment since prior chemotherapy, investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE (version 4.03) Grade 1.

13. At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.

Exclusion Criteria

1. Tumour involvement of the central nervous system

2. Uncontrolled infection or systemic disease

3. Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease, angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months

   • Patients with a QTc > 470 msec on screening ECG

4. Concurrent systemic chemotherapy or biological therapy

5. Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).

6. Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)

7. Any subject whose testosterone is not suppressed i.e. is > 0.5nmols/L

8. Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NOX66 + Radiation treatment (combined) in cohort 4	Irradiation Therapy	NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle. NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The Safety Steering Committee will inform on dose for cohort expansion. Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
NOX66 + Radiation treatment (combined) in cohorts 1-3	NOX66	NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle. NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg. Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
NOX66 + Radiation treatment (combined) in cohorts 1-3	Irradiation Therapy	NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle. NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg. Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
NOX66 + Radiation treatment (combined) in cohort 4	NOX66	NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle. NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The Safety Steering Committee will inform on dose for cohort expansion. Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events Including SAEs [Safety and Tolerability] of NOX66 Combined With Radiation Therapy at Multiple Timepoints	Day 2, Day 6, EOT (Day 16), Week 6, Week 12, and Week 24	Safety will be assessed through reported incidence of treatment emergent adverse events (AEs), including SAEs, dose limiting toxicities, AEs leading to withdrawal, events that are greater than CTCAE Version 4.03 Grade 2 in severity. Treatment emergent AEs are those with an onset on or after the initiation of therapy. Timepoints for AE /SAE assessment are Day 2 (start of radiation therapy treatment and one day after start of NOX66 treatment), Day 6, End of treatment (Day 16), Week 6, Week 12, and Week 24.
Assessment of ECG Results	Baseline to End of treatment (Day 16), Week 12, and Week 24.	Mean change from Baseline in ECG intervals (msec) which are assessed at End of treatment (Day 16), Week 12, and Week 24.
Assessment of Laboratory Results	From Baseline to End of Treatment (Day 16), Week 6, Week 12, and Week 24.	Mean change from Baseline in absolute value of safety laboratory results (haematology and biochemistry) assessed at End of Treatment (Day 16), Week 6, Week 12, and Week 24.

Secondary Outcome Measures

Name	Time	Method
Change of Target Lesions in Participants According to RECIST 1.1 Criteria	Week 6, Week 12, and Week 24	RECIST response in target irradiated and non-irradiated lesions based on radiographic CT/MRI scan. RECIST 1.1 criteria are Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD). Not Applicable (NA) indicates that a participant did not have measurable target lesions at Screening.
Change in Overall Pain Score Using the Brief Pain Inventory - Short Form (BPI-SF)	From enrolment up to Day 16, Week 6, Week 12, and Week 24	Percentage change from baseline in overall pain score based on responses to the BPI-SF, which is scored from 0 to 10, with 0 = no pain and 10 = the most severe pain imaginable.
Assessment of Change in Physical Appearance (Physical Exam) by Measuring HEENT, Gastrointestinal, Abdominal Status at Multiple Timepoints	From enrolment up to Day 2, End of Treatment (Day 16), Week 6, Week 12, and Week 24	Assessment of patient via physical exam comparing Day 2, End of Treatment (Day 16), Week 6, Week 12, and Week 24 to baseline. Physical exam included abdominal, cardiovascular, dermatologic, gastrointestinal, genitourinary, HEENT (head, eyes, ears, nose, throat), lymphatic, musculoskeletal, neurological, other, and pulmonary exams.
Change of Non-Target Lesions in Participants According to RECIST 1.1 Criteria	Week 6, Week 12, and Week 24	RECIST 1.1 assessment of response in Non-Target Lesions as Complete Response (CR), Non-CR/Non-PD, or Progressive Disease (PD). Not Applicable (NA) signifies that the participant did not have non-target lesions at Screening.
Overall Response According to RECIST 1.1 Criteria	From enrolment up to Week 6, Week 12, and Week 24	Overall RECIST 1.1 response based on combined assessment criteria for target, non-target and new lesions as Complete Response (CR), Partial Response (PR), Stable Disease(SD), or Progressive Disease (PD)
Change in Prostate Specific Antigen (PSA) Levels	From enrolment up to Week 6, Week 12, and Week 24	Percentage change from baseline in serum PSA levels (ng/mL) at Week 6, Week 12, and Week 24
Change of ECOG Performance Status	From enrolment up to Week 6, Week 12, and Week 24	Assessment of patient via ECOG Performance Status, which has a scale scored from 0 (Fully Active) to 5 (Dead).

Trial Locations

Locations (10)

Genesis Cancer Care - Newcastle; 🇦🇺 Newcastle, New South Wales, Australia

Central West Cancer Care Centre - Orange Health Service; 🇦🇺 Orange, New South Wales, Australia

Genesis Cancer Care Mater Hospital; 🇦🇺 Sydney, New South Wales, Australia

North West Cancer Centre, Tamworth Hospital; 🇦🇺 Tamworth, New South Wales, Australia

Radiation Oncology Centres Gold Coast; 🇦🇺 Gold Coast, Queensland, Australia

Research Institute of Clinical Medicine; 🇬🇪 Tbilisi, Georgia

TSMU The First University Clinic; 🇬🇪 Tbilisi, Georgia

National Center of Urology; 🇬🇪 Tbilisi, Georgia

Institute for Personalised Medicine; 🇬🇪 Tbilisi, Georgia

Canterbury Urology Research Trust; 🇳🇿 Christchurch, New Zealand