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

Cancer Clinical Trial

Official title:

NOX66 and Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer - a Phase 1b Proof of Concept and Dose Confirmation Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03307629
• Other study ID #: NOX66-002A
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2017
• Est. completion date: September 15, 2020

Study information

• Verified date: March 2020
• Source: Noxopharm Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 15, 2020
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Prostatic Neoplasms

Intervention

Drug:
• NOX66
NOX66 delivered as rectal suppository.

Radiation:
• Irradiation Therapy
Radiation per selected tumour lesion.

Locations

Country	Name	City	State
Australia	Radiation Oncology Centres Gold Coast	Gold Coast	Queensland
Australia	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
Georgia	Institute for Personalised Medicine	Tbilisi
Georgia	National Center of Urology	Tbilisi
Georgia	Research Institute of Clinical Medicine	Tbilisi
Georgia	TSMU The First University Clinic	Tbilisi
New Zealand	Canterbury Urology Research Trust	Christchurch

Sponsors (1)

Lead Sponsor	Collaborator
Noxopharm Limited

Countries where clinical trial is conducted

Australia,  Georgia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of incidence of Treatment-Emergent Adverse Events including SAEs [Safety and Tolerability] of NOX66 combined with radiation therapy between multiple timepoints	Safety will be assessed through reported incidence of treatment emergent adverse events (AEs), including SAEs, dose limiting toxicities, AEs leading to withdrawal, events of at least 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 16-17) and from enrolment up to week 6, week 12, week 24.	Day 2, Day 6, EOT and from enrolment up to week 6, week 12, week 24
Primary	Assessment of laboratory results	Other safety endpoints include laboratory results which are assessed at Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.	Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.
Primary	Assessment of ECG results	Further safety endpoints include laboratory results and ECG findings which are assessed Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.	Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.
Secondary	Change of tumour size in patients according to RECIST 1.1 criteria	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)	From enrolment up to week 6, week 12, week 24
Secondary	Change of non-target lesions according to RECIST 1.1 criteria	RECIST 1.1 assessment of response in Non-target lesions	From enrolment up to week 6, week 12, week 24
Secondary	Overall response according to RECIST 1.1 criteria	Overall RECIST 1.1 response based on combined assessment criteria for target, non-target and new lesions lesions as Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD)	From enrolment up to week 6, week 12, week 24
Secondary	Change in overall pain score assessment by using BPI-SF	Change from baseline in pain score based on responses to BPI-SF	From enrolment up to week 6, week 12, week 18, week 24
Secondary	Increase or decrease of Prostate Specific Antigen (PSA) levels	Change from baseline in serum PSA levels	From enrolment up to week 6, week 12, week 24
Secondary	Change of ECOG value	Assessment of patient via ECOG status	From enrolment up to week 6, week 12, week 24
Secondary	Assessment of change in physical appearance (physical exam) by measuring HEENT, gastrointestinal, abdominal status on multiple timepoints	Assessment of patient via physical exam.	From enrolment up to Day 2, End of Treatment (day 16-17), week 6, week 12, week 24