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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Type of registration
Retrospectively registered

Titles & IDs
Public title
Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma
Scientific title
Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma: a Phase II Trial (ANZUP 1601)
Secondary ID [1] 293145 0
Secondary ID [2] 293146 0
Secondary ID [3] 293147 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Kidney Cancer 305121 0
Renal Cell Carcinoma, Clear Cell 305122 0
Condition category
Condition code
Cancer 304441 304441 0 0

Study type
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab plus denosumab

Experimental: Pembrolizumab plus Denosumab - Pembrolizumab 200 mg intravenously every 3 weeks plus denosumab 120 mg subcutaneously on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D (doses at the discretion of treating clinician) commencing at start commencement of study treatment, continued until disease progression or prohibitive toxicity

Adherence will be reported by hospital staff if there are any issues with onsite administration.

Intervention code [1] 299394 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group

Primary outcome [1] 303686 0
Objective tumour response - The objective tumour response rate, as assessed by RECIST1.1 - This is defined as the proportion of participants in the analysis set with a confirmed complete response (CR) or partial response (PR) divided by the number of participants in the analysis set.
Timepoint [1] 303686 0
Performed week 12, 18, 24 and every 12 weeks through to study completion, on average 3.5years
Secondary outcome [1] 339844 0
Progression-free survival (PFS) - Progression-free survival is defined as proportion alive and progression-free at 6 months, RECIST 1.1, iRECIST
Timepoint [1] 339844 0
Performed week 12, 18, 24 and every 12 weeks through to study completion, on average 3.5years
Secondary outcome [2] 339845 0
Disease control rate (DCR) - Disease control rate is defined the proportion in Complete response, partial response or sustained disease at 6 months (iRECIST) rate (DCRR)
Timepoint [2] 339845 0
Performed week 12, 18, 24 and every 12 weeks through to study completion, on average 3.5years
Secondary outcome [3] 339846 0
Time to objective tumour response (OTR) - Objective tumour response is defined as duration of OTR using RECIST 1.1 and iRECIST
Timepoint [3] 339846 0
Performed week 12, 18, 24 and every 12weeks through to study completion, on average 3.5years
Secondary outcome [4] 339847 0
Time to first skeletal related event (SRE) - This is defined as the interval from date of registration to the date of first evidence of first skeletal related event.
Skeletal related events (SRE) are defined as pathologic fractures, spinal cord compression, requirement for radiation therapy, surgery to the bone, and hypercalcaemia of malignancy.
Timepoint [4] 339847 0
Performed every 3 weeks from study commencement through to study completion, on average 3.5years
Secondary outcome [5] 339848 0
Frequency and severity of adverse events - The number of patients with adverse events, particularly immune-related adverse events, that are related to study drug, as assessed and graded according to CTCAE v4.03
Timepoint [5] 339848 0
Performed every 3 weeks from time of patient registration, until 100 days after the last dose of treatment
Secondary outcome [6] 339849 0
Frequency of treatment delays and discontinuation due to toxicity - The number of participants with permanent discontinuation of treatment or delays due to toxicity, as assessed and graded according to CTCAE v4.03
Timepoint [6] 339849 0
Performed every 3 weeks from time of patient registration, until 30 days after the last dose of treatment

Key inclusion criteria
- Adults, aged 18 years and older, with histologically confirmed unresectable or
metastatic renal cell carcinoma with a clear cell component

- Disease progression during or after VEGFR TKI treatment

- At least 1 target lesion according to RECIST v1.1

- ECOG performance status of 0-2

- Adequate bone marrow function (done within 14 days prior to registration

- Haemoglobin greater than or equal to 90g/L

- Platelet greater than or equal to 75x109/L

- Neutrophil count greater than or equal to 1.5x109/L

- Adequate liver function (done within 14 days prior to registration and with values
within the ranges specified below):

- Bilirubin less than or equal too 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's

- AST or ALT less than or equal too 3.0 x ULN (or less than or equal too 5.0x ULN in the presence of liver metastases)

- Adequate renal function (done within 14 days prior to registration and with values
within the ranges specified below):

- Creatinine less than or equal to 1.5x ULN OR

- Creatinine clearance (CrCl) greater than or equal to 30mL/min

- Serum calcium or albumin-adjusted serum calcium greater than or equal to 2.0 mmol/L

- Tumour tissue available for tertiary correlative studies

- Willing and able to start treatment within 14 days of registration, and to comply with
all study requirements, including the timing and/or nature of the required treatment
and assessments

- Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
- Prior treatment with pembrolizumab, or with any other anti-PD-1, anti-PD-L1,
Anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting
T cell co-stimulation or immune checkpoint pathways

- Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

- Any condition requiring systemic treatment with either corticosteroids (>10mg daily
prednisone or equivalent dose of alternative corticosteroid) or other
immunosuppressive medications within 14 days of pembrolizumab administration.
Intranasal, inhaled or topical steroids are permitted in the absence of active
autoimmune disease.

- Prior treatment with denosumab.

- Untreated brain or leptomeningeal metastases or current clinical or radiological
progression of known brain metastases, or requirement for steroid therapy for brain
metastases. Patients with treated brain metastases are eligible if they have been
stable and off steroids for over than or equal too 3 weeks.

- Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis,
tuberculosis, or primary immunodeficiency

- Active infection requiring systemic therapy within 14 days before the first dose of

- Receipt of live attenuated vaccination within 30 days of the planned first dose of

- Active dental or jaw condition that precludes administration of denosumab:

i) Significant dental/oral disease, including prior history or current evidence of
osteonecrosis/osteomyelitis of the jaw, or; ii) Active dental or jaw condition which
requires oral surgery, or; iii) Non-healed dental/oral surgery, or; iv) Planned
invasive dental procedures during the course of the study

- Clinically significant hypersensitivity to denosumab or any components of denosumab

- Targeted small molecule therapy, surgery or radiation therapy within 2 weeks before
registration, or persisting adverse event(s) of Grade 2 or more due to a previously
administered agent. Note that participants who have had recent major surgery must have
recovered adequately before registration.

- Life expectancy of less than 3 months.

- History of an active malignancy within the previous 5 years, except for locally
curable cancers that have been apparently cured, such as low-grade thyroid carcinoma,
prostate cancer not requiring treatment (Gleason grade less than or equal too 6), basal or squamous cell
skin cancer, superficial bladder cancer, melanoma in situ, or carcinoma in situ of the
prostate, cervix, or breast. Patients who have been free of other malignancies for greater than or equal than 5 years prior to registration are eligible for this study.

- Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. -
Serious medical or psychiatric conditions that might limit the ability of the patient
to comply with the protocol

- Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal,
infertile, or use a reliable means of contraception. Women of childbearing potential
must have a negative pregnancy test done within 7 days prior to registration. Men must
have been surgically sterilised or use a (double if required) barrier method of
contraception. Subject is excluded if pregnant or breast feeding, or planning to
become pregnant within 5 months after the end of treatment. Female subject of child
bearing potential is excluded if they are not willing to use, in combination with her
partner, highly effective contraception during treatment and for 5 months after the
end of treatment.

Study design
Purpose of the study
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
Single group
Other design features
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 9530 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 9531 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 9533 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [4] 9534 0
Northern Cancer Institute - St Leonards
Recruitment hospital [5] 9535 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [6] 9536 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [7] 9537 0
Concord Repatriation Hospital - Concord
Recruitment hospital [8] 9538 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [9] 9539 0
St George Hospital - Kogarah
Recruitment hospital [10] 9540 0
Box Hill Hospital - Box Hill
Recruitment hospital [11] 10855 0
Icon Cancer Care Wesley - Auchenflower
Recruitment hospital [12] 11252 0
Ballarat Oncology and Haematology Services - Wendouree
Recruitment hospital [13] 16117 0
Border Medical Oncology - Albury
Recruitment hospital [14] 16118 0
The Townsville Hospital - Douglas
Recruitment hospital [15] 16119 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 18282 0
5042 - Bedford Park
Recruitment postcode(s) [2] 18283 0
2298 - Waratah
Recruitment postcode(s) [3] 18285 0
4029 - Herston
Recruitment postcode(s) [4] 18286 0
2065 - St Leonards
Recruitment postcode(s) [5] 18287 0
4575 - Birtinya
Recruitment postcode(s) [6] 18288 0
6150 - Murdoch
Recruitment postcode(s) [7] 18289 0
2139 - Concord
Recruitment postcode(s) [8] 18290 0
3168 - Clayton
Recruitment postcode(s) [9] 18291 0
2217 - Kogarah
Recruitment postcode(s) [10] 18292 0
3128 - Box Hill
Recruitment postcode(s) [11] 22599 0
4066 - Auchenflower
Recruitment postcode(s) [12] 23129 0
3355 - Wendouree
Recruitment postcode(s) [13] 29636 0
2640 - Albury
Recruitment postcode(s) [14] 29637 0
4814 - Douglas
Recruitment postcode(s) [15] 29638 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 297773 0
Commercial sector/Industry
Name [1] 297773 0
Merck Sharp and Dohme
Address [1] 297773 0
Level 1, 26 Talavera Road
Macquarie Park NSW 2113
Country [1] 297773 0
Funding source category [2] 298219 0
Commercial sector/Industry
Name [2] 298219 0
Amgen Australia Pty Limited
Address [2] 298219 0
Level 7, 123 Epping Road, North Ryde, NSW 2113
Country [2] 298219 0
Primary sponsor type
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Level 6, Lifehouse Building, 119-143 Missenden Road, Camperdown NSW 2050
Secondary sponsor category [1] 297325 0
Name [1] 297325 0
Address [1] 297325 0
Country [1] 297325 0

Ethics approval
Ethics application status
Ethics committee name [1] 298834 0
Sydney Local Health District HREC - RPAH
Ethics committee address [1] 298834 0
Level 11, Kgv Building, Missenden Road, Camperdown New South Wales 2050
Ethics committee country [1] 298834 0
Date submitted for ethics approval [1] 298834 0
Approval date [1] 298834 0
Ethics approval number [1] 298834 0

Brief summary
This study is designed to test the safety and potential benefit of adding an existing drug used for bone protection (denosumab) to a new immune stimulating drug (pembrolizumab).

Who is it for?
You may be eligible for this study if you have a confirmed unresectable or metastatic clear cell renal carcinoma, and you have adequate liver and bone function.

Study details
All participants will receive the two study drugs, along with vitamin D and calcium (mode of administration up to the discretion of the treating clinician). Treatment will continue until disease progression or toxicity. Patients will be monitored for tumour response and skeleton health.
It is hoped this combination of medications will be as safe, and provide more benefit than the immune stimulating drug alone in treating kidney cancer.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 78382 0
Dr Craig Gedye
Address 78382 0
Calvary Mater Newcastle
Medical Oncology Trial Unit
L4 New Med Building
Edith Street
Waratah, 2298
Country 78382 0
Phone 78382 0
+61 2 9562 5000
Fax 78382 0
Email 78382 0
Contact person for public queries
Name 78383 0
Ms Nisha Rana
Address 78383 0
ANZUP Level 6, Lifehouse Building, 119-143 Missenden Road, Camperdown NSW 2050
Country 78383 0
Phone 78383 0
+6128036 5271
Fax 78383 0
Email 78383 0
Contact person for scientific queries
Name 78384 0
Ms Amasy Alkhateeb
Address 78384 0
NHMRC CTC, level 6, Lifehouse, 119-143 Missenden Rd, Camperdown, NSW 2050
Country 78384 0
Phone 78384 0
+61 2 9562 5000
Fax 78384 0
Email 78384 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results