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Trial registered on ANZCTR


Registration number
ACTRN12621001537842
Ethics application status
Approved
Date submitted
26/08/2021
Date registered
10/11/2021
Date last updated
10/11/2021
Date data sharing statement initially provided
10/11/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Safety and Efficacy of NOX66 in combination with Nivolumab for
patients with solid tumours – a pilot study (IONIC-1).
Scientific title
Safety and Efficacy of NOX66 in combination with Nivolumab for patients with solid tumours – a pilot study (IONIC-1).
Secondary ID [1] 305023 0
NOX66-IS-002
Secondary ID [2] 305766 0
CA209-66P,
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with solid tumours 323195 0
Condition category
Condition code
Cancer 320777 320777 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase I/II, open-label, non-randomised study of NOX66 in patients with solid tumours who can also be treated with nivolumab.

Two groups of participants will be recruited to the study and will be enrolled in parallel with a total of 30 participants:
- Group 1: Patients who are already receiving a checkpoint inhibitor and have minor disease progression. The current checkpoint inhibitor will be switched to nivolumab and NOX66 will be added. The study aim in the first group is to determine whether the addition of NOX66 to nivolumab specifically can convert a non-response to checkpoint inhibitors into a response.

- Group 2: Patients with minor progression on chemo- or targeted therapy and with tumour types that may not respond to nivolumab alone. These patients will be naïve to checkpoint inhibitors. After 1 cycle of NOX66 monotherapy, patients will be treated with the combination therapy – NOX66 and nivolumab. The study aim in the second group is to determine whether patients will respond to the combination treatment.

Within each group there will be dose escalation of NOX66 and dose expansion. Three doses of NOX66 will be evaluated during the dose escalation phase of the study. The first 3 patients in each group will receive the lowest dose level, 1200mg. The second and third anticipated dose levels are 1800mg and 2400mg, respectively. Safety data in each group will be assessed after 3 patients have completed 1 cycle of combination treatment (NOX66 plus nivolumab). In Group 1, this will occur after 3 patients have completed 1 x 14 day cycle. In Group 2, this will occur after 3 patients have completed 2 x 14 day cycles. Patients will remain on their assigned NOX66 dose level for the duration of the study. Data from the dose escalation phase will determine the dose used in the dose expansion phase. In dose expansion, the highest NOX66 dose that is safe and well tolerated will be assigned to the remaining patients in each group.

NOX66 is formulated as a suppository and will be rectally administered on Days 1 to 7 of each cycle, with a NOX66–free period from Days 8 to 14. A cycle duration is 14 days. Compliance will be assessed at each cycle and patients will be required to complete a paper dosing diary.

Nivolumab (240 mg) will be given intravenously on Day 1 of each cycle, starting at either Cycle 1 (in Group 1) or Cycle 2 (in Group 2). The nivolumab dose will be fixed during the study unless dose delay or discontinuation is required.

Combination treatment will continue until disease progression, unacceptable toxicity, consent withdrawal or study completion. Patients will be administered nivolumab and NOX66 for a maximum period of 2 years.
Intervention code [1] 321420 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328589 0
Safety and tolerability of NOX66 in combination with nivolumab. Safety and tolerability will be assessed using standard Adverse Event criteria for cancer trials (NCI CTCAE V5.0).
Timepoint [1] 328589 0
Adverse events will be assessed for all participants at the end of each cycle and at the End of Study or at Early Termination (Maximum 24 months).
Secondary outcome [1] 399552 0
Clinical and radiological response (CT/MRI scans) will be measured in all participants based on RECIST v1.1 and iRECIST criteria.
Timepoint [1] 399552 0
Response for all participants will be reviewed at 2, 4, 6, 12 and 18 months after the start of Cycle 1, and at the End of Study (Month 24) or Early Termination (ET).
Secondary outcome [2] 399553 0
Progression Free survival (PFS) determined by CT/MRI scans. PFS will be defined as the time in months from initial treatment until disease progression or censoring. Patients who are lost to follow-up or are alive and have not displayed disease progression will be censored at the time of their last contact with study personnel. Patients who leave the study to begin an alternative therapy will be censored on their day of study discontinuation.
Timepoint [2] 399553 0
CT/MRI scans for disease evaluation will take place at 2, 4, 6, 12 and 18 months after the start of Cycle 1, and at the End of Study (Month 24) or Early Termination (ET).
Secondary outcome [3] 400172 0
Overall Survival
Timepoint [3] 400172 0
Overall survival (OS) will be defined in months from initial treatment until death from any cause or censoring. All patients will be actively followed up every 3 months after commencing study treatment. The total follow up period is 24 months.
Secondary outcome [4] 402428 0
Burden of bone disease in patients with bony metastases.
Timepoint [4] 402428 0
A bone scan will be obtained at Screening (unless a scan within 6 weeks is available), then at 6, 12, 18 and 24 Months after the start of Cycle 1.

Eligibility
Key inclusion criteria
Key Inclusion criteria
- Adult patients with histologically confirmed diagnosis of solid metastatic tumours that are potentially amenable to treatment with nivolumab
- Measurable disease by CT/MRI imaging according to iRECIST and RECIST v1.1
- Patients must have minor disease progression following at least 8 weeks of treatment with a specific checkpoint inhibitor or minor progression whilst on treatment with either chemotherapy or a targeted therapy.
- Adequate hepatic, renal and marrow function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0–2
- Anticipated life-expectancy of at least 6 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Key Exclusion criteria
- Chemo-, immuno- or radiotherapy or surgery <28 days of enrolment. Subjects administered one of the specific checkpoint inhibitors prior to screening will still be eligible if the last dose was taken 14 to 28 days prior to Day 1 Cycle 1.
- Progressive disease on the treatment just prior to study entry that suggests rapid onset of treatment resistance
- > Grade 1 toxicity due to checkpoint inhibitors
- Tumour involvement of the central nervous system
- Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
- Uncontrolled infection or systemic disease
- Clinically significant cardiac disease not well controlled with medication myocardial infarction within the last 12 months
- Concomitant second malignancies with the exception of non-melanoma skin cancers, and treated cancers of the cervix and urothelium
- Corticosteroid treatment or other immunosuppressive medications within 14 days of initiation of nivolumab. Prednisolone up to 10mg daily, or equivalent steroid dose by conversion, is allowed.
- Pregnant (positive urine pregnancy test) or lactating.
- Patients with a colostomy.
- Patients with faecal impaction, chronic idiopathic constipation, or chronic diarrhea or alternating irritable bowel disease.
- Patients with inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis).
- Uncontrolled diabetes mellitus.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size:
Up to approximately 30 patients with solid tumours will be enrolled in the study.

It is proposed this sample size will be adequate to provide a safety profile and feasibility for this combination. The primary analysis will look at safety. A secondary analysis on efficacy will also be performed, looking at tumour response as confirmed by iRECIST, overall survival, progression free survival and other parameters

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
25/10/2021
Date of last participant enrolment
Anticipated
30/09/2022
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20219 0
Southside Cancer Care Centre - Miranda
Recruitment hospital [2] 20221 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 20222 0
St George Private Hospital - Kogarah
Recruitment hospital [4] 20223 0
Sydney Adventist Hospital - Wahroonga
Recruitment postcode(s) [1] 34949 0
2228 - Miranda
Recruitment postcode(s) [2] 34951 0
2148 - Blacktown
Recruitment postcode(s) [3] 34952 0
2217 - Kogarah
Recruitment postcode(s) [4] 34953 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 309409 0
Commercial sector/Industry
Name [1] 309409 0
Noxopharm
Country [1] 309409 0
Australia
Funding source category [2] 309410 0
Commercial sector/Industry
Name [2] 309410 0
Bristol Meyers Squibb
Country [2] 309410 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Cancer Care Foundation Limited
Address
Level 3, 533 Kingsway Miranda, NSW 2228
Country
Australia
Secondary sponsor category [1] 310381 0
None
Name [1] 310381 0
Address [1] 310381 0
Country [1] 310381 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309214 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 309214 0
Ethics committee country [1] 309214 0
Australia
Date submitted for ethics approval [1] 309214 0
25/11/2020
Approval date [1] 309214 0
18/03/2021
Ethics approval number [1] 309214 0
2020-11-1217

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113370 0
Prof Paul De Souza
Address 113370 0
Southside Cancer Care Centre Level 3, 533 Kingsway Miranda, NSW 2228
Country 113370 0
Australia
Phone 113370 0
+61 2 85569303
Fax 113370 0
Email 113370 0
P.DeSouza@westernsydney.edu.au
Contact person for public queries
Name 113371 0
Luke McPherson
Address 113371 0
Cancer Care Foundation Level 3, 533 Kingsway Miranda, NSW 2228
Country 113371 0
Australia
Phone 113371 0
+61 2 85569372
Fax 113371 0
Email 113371 0
trials@cancercarefoundation.org.au
Contact person for scientific queries
Name 113372 0
Luke McPherson
Address 113372 0
Cancer Care Foundation, Level 3, 533 Kingsway Miranda, NSW 2228
Country 113372 0
Australia
Phone 113372 0
+61 2 85569372
Fax 113372 0
Email 113372 0
trials@cancercarefoundation.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.