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Trial registered on ANZCTR


Registration number
ACTRN12613000385741
Ethics application status
Approved
Date submitted
28/03/2013
Date registered
10/04/2013
Date last updated
10/04/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Radiotherapy and Ipilimumab in Metastatic Melanoma
Scientific title
Prospective trial examining safety and biological effects of combining Ipilimumab and radiotherapy in patients with metastatic melanoma.
Secondary ID [1] 282205 0
BMS ID - CA184-325
Universal Trial Number (UTN)
U1111-1141-1952
Trial acronym
RT and Ipi in Mestatstatic Melanoma
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 288724 0
Condition category
Condition code
Cancer 289079 289079 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 3mg/kg will be given intravenously commencing on day 1 of radiotherapy and will be administered weeks 1, 4, 7, and 10, for a total of 4 infusions.
Intervention code [1] 286819 0
Treatment: Drugs
Intervention code [2] 286905 0
Treatment: Other
Comparator / control treatment
This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 10mg/kg will be given intravenously commencing on day 1 of radiotherapy and will be administered weeks 1, 4, 7, and 10, for a total of 4 infusions.
Control group
Dose comparison

Outcomes
Primary outcome [1] 289186 0
To establish a toxicity profile for patients receiving Ipilimumab in combination with radiotherapy. This will be assessed by physical examination and symptom recording during treatment and at the end of treatment.
Timepoint [1] 289186 0
24 months
Primary outcome [2] 289187 0
To assess the tumour response using CT scans and Response Evaluation Criteria in Solid Tumors (RECIST) V1.1
Timepoint [2] 289187 0
24 months
Primary outcome [3] 289274 0
To assess for changes in immune response in the tumour lesions and peripheral blood. Pre and Post treatment biomarker levels will be taken from tumour biopsy's and peripheral blood.
Timepoint [3] 289274 0
24 months
Secondary outcome [1] 301978 0
To document progression free survival using CT scans and follow up appointments with physical exams.
Timepoint [1] 301978 0
24 months
Secondary outcome [2] 302142 0
To document overall survival using follow up appointments.
Timepoint [2] 302142 0
24 months

Eligibility
Key inclusion criteria
1.Voluntarily signed and dated institutional ethics committee (IEC) approved informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before performing protocol-related procedures that are not part of standard patient care.
2.Able to comply with visits/procedures required by the protocol
3.Life expectancy of at least 3 months
4.> 18 years of age
5.Good performance status (ECOG 0-1)
6.Histologically proven advanced melanoma stage IIIC or IV
7.Measurable disease by modified RECIST 1.1 criteria (irradiated index lesion not included in overall response assessment).
8.Index lesion to be irradiated is measurable by RECIST 1.1 criteria
9.Index lesion to be irradiated is amenable to biopsy
10.Adequate hematologic, renal and liver function
11.Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception (using the clinicians’ discretion) to avoid pregnancy throughout the study and for up to 12 weeks after the last dose in such a manner that the risk of pregnancy is minimized.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Symptomatic brain metastases or those treated < 3 months previously
2.Patients requiring RT to brain, or chest and abdomen where it is expected that viscera will be in field
3.Patients being recommended a higher dose of RT (e.g. 30Gy/10#)
4.Taking immunosuppressive doses of corticosteroids (>5mg of prednisolone or equivalent) or other immunosuppressant medications
5.Previous treatment with Ipilimumab
6.Previous other investigational products within last 4 weeks
7.Uncontrolled infectious diseases (HIV, Hepatitis B etc)
8.Autoimmune disease (including, but not limited to Crohn’s Disease, Ulcerative Colitis, Rheumatoid Arthritis etc)
9.Prior malignancy in last 5 years, not including basal or squamous cell carcinoma of skin

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)
The RT dose will remain constant for each patient (25 Gy in 5 daily fractions) over 1 week. No further RT will be delivered during the 4 infusions of Ipilimumab.
Two different doses of Ipilimumab will be evaluated. The initial 15 patients will receive 3 mg/kg dose. The next 15 patient will receive 10mg/kg dose. Administration of Ipilimumab will include a total of 4 infusions.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Dose Comparison Trial
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety
Statistical methods / analysis
As this is pilot study to identify toxicity and biomarkers which would then be evaluated in larger (appropriated powered) future studies, there are no formal assumptions of statistical power. The goal of this research is to confirm that systemic Ipilimumab and palliative RT is safe to give concurrently, and to identify biomarkers potentially related to tumour response in each patient’s tumour and peripheral blood. Therefore pragmatically, the sample size of 30 patients (encompassing two groups of 15 patients each receiving a different dose level of Ipilimumab) was chosen to demonstrate safety and also provide a signal for efficacy, whilst providing a translational component.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 811 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [2] 812 0
Westmead Hospital - Westmead

Funding & Sponsors
Funding source category [1] 286966 0
Commercial sector/Industry
Name [1] 286966 0
Bristol Myers Squibb
Address [1] 286966 0
Level 2, 4 Nexus Court, Mulgrave, VIC, 3170
Country [1] 286966 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
St Andrews Place, East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 285757 0
None
Name [1] 285757 0
Address [1] 285757 0
Country [1] 285757 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289015 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 289015 0
St Andrews Place, East Melbourne, VIC, 3002
Ethics committee country [1] 289015 0
Australia
Date submitted for ethics approval [1] 289015 0
04/04/2013
Approval date [1] 289015 0
Ethics approval number [1] 289015 0
HREC/13/PMCC/14.

Summary
Brief summary
This study is examining the safety and biological effects of combining Ipilimumab and radiotherapy in patients with metastatic melanoma.

Who is it for?
You may be eligible to join this study if you are aged over 18 years and have been diagnosed with advanced melanoma stage IIIc or IV.

Trial details
All participants in this trial will undergo 5 daily doses of radiotherapy during week 1. They will also receive Ipilimumab at a dose of either 3mg/kg or 10mg/kg at weeks 1, 4, 7, and 10. This drug will be administered intravenously (i.e. directly into the vein) over a period of 90 minutes.

Participants will be reviewed for up to 24 months in order to determine treatment toxicities, tumour response, and immune response.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38822 0
Dr Kathy Pope
Address 38822 0
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne
Victoria, 3002
Country 38822 0
Australia
Phone 38822 0
61 3 9656 1111
Fax 38822 0
Email 38822 0
kathy.pope@petermac.org
Contact person for public queries
Name 38823 0
Ms Tina Thorpe
Address 38823 0
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne
Victoria, 3002
Country 38823 0
Australia
Phone 38823 0
61 3 9656 1521
Fax 38823 0
Email 38823 0
tina.thorpe@petermac.org
Contact person for scientific queries
Name 38824 0
Dr Kathy Pope
Address 38824 0
Peter MacCallum Cancer Centre
St Andrews Place
East Melbourne
Victoria, 3002
Country 38824 0
Australia
Phone 38824 0
61 3 9656 1111
Fax 38824 0
Email 38824 0
kathy.pope@petermac.org

No information has been provided regarding IPD availability
Summary results
No Results