Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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:
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That NOX66 can be safely added to palliative dose radiation therapy.
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That NOX66 may sensitise tumours to palliative doses of radiation therapy
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NOX66 + Radiation treatment (combined) in cohorts 1-3 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. |
Drug: NOX66
NOX66 delivered as rectal suppository.
Radiation: Irradiation Therapy
Radiation per selected tumour lesion.
|
| Experimental: NOX66 + Radiation treatment (combined) in cohort 4 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. |
Drug: NOX66
NOX66 delivered as rectal suppository.
Radiation: Irradiation Therapy
Radiation per selected tumour lesion.
|
Outcome Measures
Primary Outcome Measures
- Change of incidence of Treatment-Emergent Adverse Events including SAEs [Safety and Tolerability] of NOX66 combined with radiation therapy between multiple timepoints [Day 2, Day 6, EOT and from enrolment up to week 6, week 12, 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 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.
- Assessment of laboratory results [Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.]
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.
- Assessment of ECG results [Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.]
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.
Secondary Outcome Measures
- Change of tumour size in patients according to RECIST 1.1 criteria [From enrolment up to week 6, week 12, 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)
- Change of non-target lesions according to RECIST 1.1 criteria [From enrolment up to week 6, week 12, week 24]
RECIST 1.1 assessment of response in Non-target lesions
- Overall response according to RECIST 1.1 criteria [From enrolment up to week 6, week 12, week 24]
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)
- Change in overall pain score assessment by using BPI-SF [From enrolment up to week 6, week 12, week 18, week 24]
Change from baseline in pain score based on responses to BPI-SF
- Increase or decrease of Prostate Specific Antigen (PSA) levels [From enrolment up to week 6, week 12, week 24]
Change from baseline in serum PSA levels
- Change of ECOG value [From enrolment up to week 6, week 12, week 24]
Assessment of patient via ECOG status
- Assessment of change in physical appearance (physical exam) by measuring HEENT, gastrointestinal, abdominal status on multiple timepoints [From enrolment up to Day 2, End of Treatment (day 16-17), week 6, week 12, week 24]
Assessment of patient via physical exam.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Provision of informed consent
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≥ 18 years of age
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Histologically confirmed prostate cancer and/or PSA of >100 ng/mL at original diagnosis
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Metastatic disease evidenced by either CT/MRI imaging or bone scan
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Objective evidence of disease progression as defined by either:
- 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.
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Eligible to receive palliative radiation therapy for management of disease
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At least one symptomatic lesion which is suitable for radiation therapy
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ECOG Performance status 0-2
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A minimum life expectancy of 24 weeks
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Adequate bone marrow, hepatic and renal function as evidenced by:
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Absolute neutrophil count (ANC) > 1.5 x 109/L
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Platelet count > 100 x 109/L
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Hemoglobin > 9.0 g/dL
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Serum bilirubin < 1.5 x ULN
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AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
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Serum creatinine < 1.5 x ULN
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Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
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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.
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At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.
Exclusion Criteria:
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Tumour involvement of the central nervous system
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Uncontrolled infection or systemic disease
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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
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Concurrent systemic chemotherapy or biological therapy
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Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).
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Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
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Any subject whose testosterone is not suppressed i.e. is > 0.5nmols/L
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Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Genesis Cancer Care - Newcastle | Newcastle | New South Wales | Australia | 2290 |
| 2 | Central West Cancer Care Centre - Orange Health Service | Orange | New South Wales | Australia | 2800 |
| 3 | Genesis Cancer Care Mater Hospital | Sydney | New South Wales | Australia | 2060 |
| 4 | North West Cancer Centre, Tamworth Hospital | Tamworth | New South Wales | Australia | 2340 |
| 5 | Radiation Oncology Centres Gold Coast | Gold Coast | Queensland | Australia | 4215 |
| 6 | Research Institute of Clinical Medicine | Tbilisi | Georgia | 0112 | |
| 7 | TSMU The First University Clinic | Tbilisi | Georgia | 0141 | |
| 8 | National Center of Urology | Tbilisi | Georgia | 0144 | |
| 9 | Institute for Personalised Medicine | Tbilisi | Georgia | 0186 | |
| 10 | Canterbury Urology Research Trust | Christchurch | New Zealand | 8013 |
Sponsors and Collaborators
- Noxopharm Limited
Investigators
- Study Chair: Marinella Messina, PhD, Noxopharm Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NOX66-002A