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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03206021


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT03206021
Ethics application status
Date submitted
21/06/2017
Date registered
2/07/2017

Titles & IDs
Public title
COZMOS:Phase I/Ib Trial of Combined 5'Azacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain/Solid Tumors
Scientific title
Phase I/Ib Trial of COmbined 5'aZacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain and Solid Tumors
Secondary ID [1] 0 0
OZM-077
Universal Trial Number (UTN)
Trial acronym
COZMOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Childhood CNS Tumor 0 0
Ependymoma, Recurrent Childhood 0 0
Childhood Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5 Azacytidine

Experimental: Phase I Dose-escalation - 5'azacytidine will be administered on Days 1-7 at a dose of 75mg/m2/day, followed by escalating doses of Carboplatin on Day 14 in a rolling 6 design. Carboplatin will be dosed initially at AUC 4. Dose level -1 will reduce 5'azacytidine to 50mg/m2/day.

Experimental: Posterior Fossa Ependymoma Expansion Arm - 5'azacytidine will be administered on days 1-7 and carboplatin will be administered on day 14 at the maximum tolerated dose achieved in the Phase I dose escalation to 20 patients with recurrent/refractory posterior fossa ependymoma.

Experimental: Recurrent Brain and Solid Tumour Expansion Arm - 5'azacytidine will be administered on days 1-7 and carboplatin will be administered on day 14 at the maximum tolerated dose achieved in the Phase I dose escalation up to 12 patients with recurrent/refractory brain and solid tumour.


Treatment: Drugs: 5 Azacytidine
Dose escalation of carboplatin combined with 5'azacytidine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Establish maximum tolerated dose of carboplatin in combination with 5'azacytidine
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
Characterization of the pharmacodynamics of 5'-azacitidine in combination with carboplatin
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Assessment of intratumoral DNA demethylation as a preliminary indication of biological efficacy of this combination.
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Assessment of disease response as a preliminary indication of efficacy of this combination against recurrent, refractory pediatric brain and solid tumors
Timepoint [3] 0 0
3 years

Eligibility
Key inclusion criteria
1. Greater than the age of 1 year and under age 18 at the time of study enrolment
2. Recurrent or refractory brain or solid tumor, including recurrent or refractory ependymoma
3. Tissue from diagnosis or resection prior to registration must be available (either flash frozen tissue or an FFPE block)
4. Previous therapy with carboplatin will be permitted
5. Failed first line treatment (surgery, radiation therapy or chemotherapy) and should not be eligible for treatment with curative potential.
6. Be at least 4 weeks from the completion of myelosuppressive chemotherapy and/or biologic agents before starting day 1 of this study treatment
7. Be at least 14 days from the completion of radiation therapy and MIBG before starting day 1 of this study treatment
8. Be at least 3 months post hematopoetic stem cell rescue following myeloablative therapy before starting day 1 of this study treatment
9. Must have visible disease on imaging. Resection of visible disease is permitted while on study after two cycles including achievement of a gross total resection. If a resection is performed while on study, fresh frozen tissue should be submitted for analysis.
10. Concurrent medications will be limited to supportive medications/agents including but not limited to anti-emetics, steroids, analgesics and non-enzyme inducing anticonvulsants. Strong inducers of the P450 system will not be permitted. Other concurrent medications require approval of the study Sponsor.
11. Ability of the parent and/or child to understand and the willingness to sign a written informed consent document
12. Karnofsky = 50 for patients > 16 years of age and Lansky = 50 for patients = 16 years of age (See Appendix I for the Karnofsky-Lansky Scores). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Patients with posterior fossa syndrome/cerebellar mutism demonstrating clear improvement post-surgically can be enrolled based on physician discretion
13. Adequate hepatic, renal, marrow and cardiac function as defined below within 28 days prior to cycle 1 day 1:

* Serum creatinine within normal institutional limits or creatinine clearance greater than 60mL/min
* Serum bilirubin <1.5 times upper limit of institutional normal. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis
* AST, ALT and Alkaline Phosphatase <3 times upper limit of institutional normal. If liver metastases are present, then <5 times upper limit of normal is permitted.
* Normal QTc interval at screening ECG (baseline echocardiogram is not required)
* Adequate marrow function defined below within 14 days prior to cycle 1 day 1:

* Leukocytes greater than or equal to 1000 x106/L
* Absolute neutrophil count greater than or equal to 0.75 x109/L
* Platelets greater than or equal to 75 x109/L
* Hemoglobin greater than or equal to 10g/dL (may be transfused).
Minimum age
1 Year
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Female patient who is pregnant or breast feeding (Lactating females must agree not to breast feed while taking azacitidine) or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 6 months after the end of study treatment.
2. Patients may not be receiving any other investigational agents within 30 days prior to day 1 of protocol treatment
3. Prior therapy with a DNA demethylase inhibitor
4. Evidence of cardiac toxicity (shortening fraction below 28%; shortening fraction measures and ratios the change in the diameter of the left ventricle between the contracted and relaxed states)
5. Abnormal coagulation parameters (PT >15 seconds, PTT>40 seconds, and/or INR >1.5)
6. Significant active cardiac disease within the previous 6 months including:

* NYHA class 3 or 4 CHF
* Unstable angina
* Myocardial infarction
7. Known or suspected hypersensitivity to azacitidine or mannitol carboplatin
8. Previous carboplatin exposure is not an exclusion criteria but previous allergic reaction to carboplatin will exclude enrolment.
9. Patient must not require use of enzyme inducing anticonvulsants; patients who are receiving an enzyme inducing anticonvulsant must be able to switch to a non-enzyme inducing anticonvulsant such as Levetiracetam, Clobazam, Lacosamide, Valproate or Topiramate at least 2 weeks prior to study enrolment.
10. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
11. Active viral infection with HIV or hepatitis type B or C Patients with advanced malignant hepatic tumors
12. Patients with advanced malignant hepatic tumors

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2024
Sample size
Target
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Children's Hospital Melbourne - Melbourne
Recruitment hospital [2] 0 0
Women's and Children's Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Children's Hospital - Clayton
Recruitment hospital [4] 0 0
John Hunter Children's Hospital - Lambton
Recruitment hospital [5] 0 0
Perth Children's Hospital - Perth
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [8] 0 0
Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
- Lambton
Recruitment postcode(s) [5] 0 0
- Perth
Recruitment postcode(s) [6] 0 0
- South Brisbane
Recruitment postcode(s) [7] 0 0
- Sydney
Recruitment postcode(s) [8] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
Country [2] 0 0
Canada
State/province [2] 0 0
Alberta
Country [3] 0 0
Canada
State/province [3] 0 0
British Columbia
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Canada
State/province [5] 0 0
PQ

Funding & Sponsors
Primary sponsor type
Other
Name
The Hospital for Sick Children
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Vijay Ramaswamy, MD PhD FRCPC
Address 0 0
The Hospital for Sick Children
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

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



Results not provided in https://clinicaltrials.gov/study/NCT03206021

Additional trial details provided through ANZCTR
Accrual to date
2
Recruiting in Australia
Recruitment state(s)
QLD,WA,VIC
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Secondary sponsor category [1] 29
Other Collaborative groups
Name [1] 29
ANZCHOG
Address [1] 29
27-31 Wright Street, Clayton VIC 3168
Country [1] 29
Australia
Ethics approval
Ethics application status
 
Public notes
Monash Children's Hospital
Perth Children's Hospital
Queensland Children's Hospital
Royal Children's Hospital

Contacts
Principal investigator
Title 145 0
Dr
Name 145 0
Jordan Hansford
Address 145 0
50 Flemington Rd, Parkville VIC 3052 AUSTRALIA
Country 145 0
Australia
Phone 145 0
+613 9345 5084
Fax 145 0
Email 145 0
Jordan.hansford@rch.org.au
Contact person for public queries
Title 146 0
Mrs
Name 146 0
Robyn Strong
Address 146 0
27-31 Wright Street, Clayton VIC 3168
Country 146 0
Australia
Phone 146 0
+613 8572 2684
Fax 146 0
+613 9902 4810
Email 146 0
Robyn.strong@hudson.org.au
Contact person for scientific queries
Title 147 0
Dr
Name 147 0
Jordan Hansford
Address 147 0
50 Flemington Rd, Parkville VIC 3052 AUSTRALIA
Country 147 0
Australia
Phone 147 0
+613 9345 5084
Fax 147 0
Email 147 0
Jordan.hansford@rch.org.au