Trial from ClinicalTrials.gov

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Trial ID
NCT03280667
Ethics application status
Date submitted
7/09/2017
Date registered
7/09/2017
Date last updated
18/01/2018

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] 0 0
20149171
Secondary ID [2] 0 0
ANZUP1601
Universal Trial Number (UTN)
Trial acronym
KEYPAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma, Clear Cell 0 0
Metastatic Kidney Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

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

Experimental: Pembrolizumab plus Denosumab - Pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D, continued until disease progression or prohibitive toxicity


Treatment: drugs: Pembrolizumab plus denosumab
Pembrolizumab 200 mg IV every 3 weeks plus denosumab 120 mg SC on day 1, 8, 22 and then every 3 weeks with daily oral calcium and vitamin D

Intervention code [1] 0 0
Treatment: drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 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] 0 0
Through study completion, on average 3.5 years
Secondary outcome [1] 0 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] 0 0
6 months
Secondary outcome [2] 0 0
Disease control rate (DCR) - Disease control rate is defined the proportion in CR, PR, or SD at 6 months iRECIST) rate (DCRR)
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Time to objective tumour response (OTR) - Objective tumour response is defined as duration of OTR using RECIST 1.1 and iRECIST
Timepoint [3] 0 0
Through study completion, on average 3.5 years
Secondary outcome [4] 0 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.
Timepoint [4] 0 0
Through study completion, on average 3.5 years
Secondary outcome [5] 0 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] 0 0
From time of patient registration, until 100 days after the last dose of treatment
Secondary outcome [6] 0 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] 0 0
From time of patient registration, until 30 days after the last dose of treatment

Eligibility
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 = 90g/L

- Platelet = 75x109/L

- Neutrophil count = 1.5x109/L

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

- Bilirubin = 1.5 x upper limit of normal (ULN) except for patients with known Gilbert's
syndrome

- AST or ALT = 3.0 x ULN (or = 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 = 1.5x ULN OR

- Creatinine clearance (CrCl) = 30mL/min

- Serum calcium or albumin-adjusted serum calcium =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
Gender
Both males and females
Can healthy volunteers participate?
No
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 = 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
pembrolizumab

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

- 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 = 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 = 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
Treatment
Allocation to intervention
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
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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,QLD,VIC
Recruitment hospital [1] 0 0
Northern Cancer Institute - Frenchs Forest
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [3] 0 0
St George - Sydney
Recruitment hospital [4] 0 0
Royal Brisbane and Womens hospital - Herston
Recruitment hospital [5] 0 0
Box Hill - Box Hill
Recruitment postcode(s) [1] 0 0
2086 - Frenchs Forest
Recruitment postcode(s) [2] 0 0
2298 - Newcastle
Recruitment postcode(s) [3] 0 0
2229 - Sydney
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
3128 - Box Hill

Funding & Sponsors
Primary sponsor type
Other
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme Corp.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Amgen
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This Single-arm, multicentre, phase 2 trial aims determine the activity and safety of
pembrolizumab and denosumab in advanced clear cell renal cell carcinoma (ccRCC).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Anne Woollett
Address 0 0
Country 0 0
Phone 0 0
61295625033
Fax 0 0
Email 0 0
anne.woollett@anzup.org.au
Contact person for scientific queries
Contact person responsible for updating information