Trial Review

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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
5/08/2022
Date data sharing statement initially provided
5/08/2022
Date results information initially provided
5/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Radiotherapy, Ipilimumab and Nivolumab in Metastatic Melanoma.
Scientific title
Prospective trial examining safety and biological effects of combining Ipilimumab and radiotherapy and Ipilimumab, Nivolumab 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, Ipi & Nivo in Mestatstatic Melanoma (RIPINIVO)
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
Cohort 1 (6 patients) 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.
Cohort 2 (subsequent 24 patients) This group involves giving 25 Gy of radiotherapy in 5 daily fractions during the first week. Ipilimumab 3mg/kg with Nivolumab 1mg/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. This will be followed by maintenance Nivolumab 3mg/kg every 2 weeks indefinitely until disease progression or unacceptable tolerance.
Intervention code [1] 286819 0
Treatment: Drugs
Intervention code [2] 286905 0
Treatment: Other
Comparator / control treatment
No control group.
The two cohorts were not directly compared as the goal of the study was to confirm that systemic Ipilimumab, and Nivolumab & Ipilimumab with palliative RT was safe to give concurrently.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289186 0
Correction as this outcomes was assessed in both cohorts:
To establish a toxicity profile for patients receiving Ipilimumab and combination Ipilimumab + Nivolumab together with palliative radiotherapy.
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
Secondary outcome [3] 412609 0
To document overall tumour response using CT scans.
Timepoint [3] 412609 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
Sex
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, nivolumab or Pembrolizumab
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 active within the previous 3 years, except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
10. Prior allogenic stem cell transplant
11. History of immunodeficiency

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
Other
Other design features
The first 6 patients were enrolled on study with Ipilimumab + radiotherapy. A major protocol amendment was implemented and the subsequent 24 patients were enrolled to receive ipilimumab + nivolumab + radiotherapy.
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
As this is pilot study to identify toxicity and biomarkers that 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 Nivolumab &
Ipilimumab with 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 (6 patients from cohort 1 and 24
patients from cohort 2) was chosen to demonstrate safety and also provide a signal for
efficacy, whilst providing a translational component. The original intent was to recruit 15
patients in each cohort, however given the change in treatment landscape the recruitment
for cohort 1 will cease after 6 patients and all the remaining patients will be recruited to
cohort 2.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/06/2013
Actual
1/09/2014
Date of last participant enrolment
Anticipated
Actual
15/06/2018
Date of last data collection
Anticipated
Actual
22/05/2020
Sample size
Target
30
Accrual to date
Final
20
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
Recruitment hospital [3] 22916 0
The Poche Centre, Melanoma Institute Australia - North Sydney

Funding & Sponsors
Funding source category [1] 286966 0
Commercial sector/Industry
Name [1] 286966 0
Bristol Myers Squibb
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
22/07/2013
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, or combining Ipilimmab, Nivolumab 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
6 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.

24 patients in this trial will undergo 5 daily doses of radiotherapy during week 1. They will also receive Nivolumab at a dose of 1,g/kg together with Ipilimumab at a dose of 3mg/kg at weeks 1, 4, 7 and 10. This group will also receive Nivolumab 3mg/kg every 2 weeks after as maintenance. These drugs will be administered intravenously (i.e directly into the vein).

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 Shahneen Sandhu
Address 38822 0
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne VIC 3000
Country 38822 0
Australia
Phone 38822 0
+61 0385597899
Fax 38822 0
Email 38822 0
[email protected]
Contact person for public queries
Name 38823 0
Ms Ruth Columbus
Address 38823 0
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne VIC 3000
Country 38823 0
Australia
Phone 38823 0
+61 0385595000
Fax 38823 0
Email 38823 0
[email protected]
Contact person for scientific queries
Name 38824 0
Dr Shahneen Sandhu
Address 38824 0
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne VIC 3000
Country 38824 0
Australia
Phone 38824 0
+61 0385595000
Fax 38824 0
Email 38824 0
[email protected]

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


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.