Back to resultsSafety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer
Primary Purpose
Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
NOX66
Irradiation Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Cancer
Eligibility Criteria
Inclusion Criteria:
- Provision of informed consent
- ≥ 18 years of age
- Histologically confirmed prostate cancer and/or PSA of >100 ng/mL at original diagnosis
- Metastatic disease evidenced by either CT/MRI imaging or bone scan
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.
- Eligible to receive palliative radiation therapy for management of disease
- At least one symptomatic lesion which is suitable for radiation therapy
- ECOG Performance status 0-2
- A minimum life expectancy of 24 weeks
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
- Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
- 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.
- At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.
Exclusion Criteria:
- Tumour involvement of the central nervous system
- Uncontrolled infection or systemic disease
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
- Concurrent systemic chemotherapy or biological therapy
- Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).
- Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
- Any subject whose testosterone is not suppressed i.e. is > 0.5nmols/L
- Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.
Sites / Locations
- Genesis Cancer Care - Newcastle
- Central West Cancer Care Centre - Orange Health Service
- Genesis Cancer Care Mater Hospital
- North West Cancer Centre, Tamworth Hospital
- Radiation Oncology Centres Gold Coast
- Research Institute of Clinical Medicine
- TSMU The First University Clinic
- National Center of Urology
- Institute for Personalised Medicine
- Canterbury Urology Research Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
NOX66 + Radiation treatment (combined) in cohorts 1-3
NOX66 + Radiation treatment (combined) in cohort 4
Arm Description
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 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.
Outcomes
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
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
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
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
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
RECIST 1.1 assessment of response in Non-target lesions
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)
Change in overall pain score assessment by using BPI-SF
Change from baseline in pain score based on responses to BPI-SF
Increase or decrease of Prostate Specific Antigen (PSA) levels
Change from baseline in serum PSA levels
Change of ECOG value
Assessment of patient via ECOG status
Assessment of change in physical appearance (physical exam) by measuring HEENT, gastrointestinal, abdominal status on multiple timepoints
Assessment of patient via physical exam.
Full Information
NCT ID
NCT03307629
First Posted
September 27, 2017
Last Updated
September 20, 2020
Sponsor
Noxopharm Limited
1. Study Identification
Unique Protocol Identification Number
NCT03307629
Brief Title
Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer
Official Title
NOX66 and Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer - a Phase 1b Proof of Concept and Dose Confirmation Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
December 1, 2019 (Actual)
Study Completion Date
September 15, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Noxopharm Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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:
That NOX66 can be safely added to palliative dose radiation therapy.
That NOX66 may sensitise tumours to palliative doses of radiation therapy
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NOX66 + Radiation treatment (combined) in cohorts 1-3
Arm Type
Experimental
Arm Description
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.
Arm Title
NOX66 + Radiation treatment (combined) in cohort 4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
NOX66
Intervention Description
NOX66 delivered as rectal suppository.
Intervention Type
Radiation
Intervention Name(s)
Irradiation Therapy
Intervention Description
Radiation per selected tumour lesion.
Primary Outcome Measure Information:
Title
Change of incidence of Treatment-Emergent Adverse Events including SAEs [Safety and Tolerability] of NOX66 combined with radiation therapy between multiple timepoints
Description
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.
Time Frame
Day 2, Day 6, EOT and from enrolment up to week 6, week 12, week 24
Title
Assessment of laboratory results
Description
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.
Time Frame
Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.
Title
Assessment of ECG results
Description
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.
Time Frame
Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.
Secondary Outcome Measure Information:
Title
Change of tumour size in patients according to RECIST 1.1 criteria
Description
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)
Time Frame
From enrolment up to week 6, week 12, week 24
Title
Change of non-target lesions according to RECIST 1.1 criteria
Description
RECIST 1.1 assessment of response in Non-target lesions
Time Frame
From enrolment up to week 6, week 12, week 24
Title
Overall response according to RECIST 1.1 criteria
Description
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)
Time Frame
From enrolment up to week 6, week 12, week 24
Title
Change in overall pain score assessment by using BPI-SF
Description
Change from baseline in pain score based on responses to BPI-SF
Time Frame
From enrolment up to week 6, week 12, week 18, week 24
Title
Increase or decrease of Prostate Specific Antigen (PSA) levels
Description
Change from baseline in serum PSA levels
Time Frame
From enrolment up to week 6, week 12, week 24
Title
Change of ECOG value
Description
Assessment of patient via ECOG status
Time Frame
From enrolment up to week 6, week 12, week 24
Title
Assessment of change in physical appearance (physical exam) by measuring HEENT, gastrointestinal, abdominal status on multiple timepoints
Description
Assessment of patient via physical exam.
Time Frame
From enrolment up to Day 2, End of Treatment (day 16-17), week 6, week 12, week 24
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of informed consent
≥ 18 years of age
Histologically confirmed prostate cancer and/or PSA of >100 ng/mL at original diagnosis
Metastatic disease evidenced by either CT/MRI imaging or bone scan
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.
Eligible to receive palliative radiation therapy for management of disease
At least one symptomatic lesion which is suitable for radiation therapy
ECOG Performance status 0-2
A minimum life expectancy of 24 weeks
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
Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
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.
At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.
Exclusion Criteria:
Tumour involvement of the central nervous system
Uncontrolled infection or systemic disease
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
Concurrent systemic chemotherapy or biological therapy
Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).
Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
Any subject whose testosterone is not suppressed i.e. is > 0.5nmols/L
Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marinella Messina, PhD
Organizational Affiliation
Noxopharm Limited
Official's Role
Study Chair
Facility Information:
Facility Name
Genesis Cancer Care - Newcastle
City
Newcastle
State/Province
New South Wales
ZIP/Postal Code
2290
Country
Australia
Facility Name
Central West Cancer Care Centre - Orange Health Service
City
Orange
State/Province
New South Wales
ZIP/Postal Code
2800
Country
Australia
Facility Name
Genesis Cancer Care Mater Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2060
Country
Australia
Facility Name
North West Cancer Centre, Tamworth Hospital
City
Tamworth
State/Province
New South Wales
ZIP/Postal Code
2340
Country
Australia
Facility Name
Radiation Oncology Centres Gold Coast
City
Gold Coast
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Research Institute of Clinical Medicine
City
Tbilisi
ZIP/Postal Code
0112
Country
Georgia
Facility Name
TSMU The First University Clinic
City
Tbilisi
ZIP/Postal Code
0141
Country
Georgia
Facility Name
National Center of Urology
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
Institute for Personalised Medicine
City
Tbilisi
ZIP/Postal Code
0186
Country
Georgia
Facility Name
Canterbury Urology Research Trust
City
Christchurch
ZIP/Postal Code
8013
Country
New Zealand
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data for primary and secondary outcome measure will be made available within 12 months after study completion.
IPD Sharing Time Frame
12 months after study completion
Learn more about this trial
Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer
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