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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03177239




Trial ID
NCT03177239
Ethics application status
Date submitted
4/06/2017
Date registered
4/06/2017
Date last updated
2/04/2018

Titles & IDs
Public title
Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602)
Scientific title
A Phase II Sequential Treatment Trial of Single Agent Nivolumab, Then Combination Ipilimumab + Nivolumab in Metastatic or Unresectable Non-Clear Cell Renal Cell Carcinoma (ANZUP1602).
Secondary ID [1] 0 0
ANZUP 1602
Universal Trial Number (UTN)
Trial acronym
UNISoN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Papillary Renal Cell Carcinoma Type 1 0 0
Papillary Renal Cell Carcinoma Type 2 0 0
Chromophobe Renal Cell Carcinoma 0 0
Sarcomatoid Renal Cell Carcinoma 0 0
Xp11 Translocation Carcinoma 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 - Nivolumab
Treatment: Drugs - Ipilimumab

Experimental: Nivolumab and Ipilimumab - Part 1: nivolumab 240mg IV q2w for a maximum of 12 months.
Part 2; nivolumab 240mg IV q3w in addition to ipilimumab 1mg/kg q3w x 4 cycles Then nivolumab 240mg q2w for a maximum of 12 months.


Treatment: Drugs: Nivolumab
Dosage Form: Nivolumab BMS-936558-01 Solution for Injection Potency: 100 mg (10 mg/mL) Primary Packaging: 10 mL vial Appearance: Clear to opalescent colourless to pale yellow liquid. May contain particles.
Storage Condition: 2 to 8°C. Protect from light and freezing.

Treatment: Drugs: Ipilimumab
Dosage Form: Ipilimumab Solution for Injection Potency: 200 mg (5 mg/mL) Primary Packaging: 40 mL vial Appearance: Clear, colourless to pale yellow liquid. May contain particles. Storage Condition: 2 to 8°C. Protect from light and freezing.

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

Outcomes
Primary outcome [1] 0 0
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 5 years.
Secondary outcome [1] 0 0
Duration of objective tumour response, as assessed by RECIST1.1 - Measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease is objectively documented.
Timepoint [1] 0 0
Through study completion, on average 5 years.
Secondary outcome [2] 0 0
Progression-free survival (PFS), as assessed by RECIST1.1 - For Part 1, PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death, whichever occurs first. For Part 2, PFS is defined as the interval from date of progressive disease on nivolumab monotherapy until the date of first evidence of disease progression or death, whichever occurs first.
Timepoint [2] 0 0
Through study completion, on average 5 years.
Secondary outcome [3] 0 0
Immune-related tumour response rate, as assessed by irRECIST. - Defined as the proportion of participants in the analysis set with an immune related complete response (irCR), or immune related partial response (irPR), divided by the number of participants in the analysis set.
Timepoint [3] 0 0
Through study completion, on average 5 years.
Secondary outcome [4] 0 0
Immune-related disease control rate (irDCR6), as assessed by irRECIST. - For Part 1, irDCR6 is defined as an assessment of CR or iPR or iSD according to modified irRECIST. For Part 2, irDCR6 is defined in the same way except that the extent of disease defining the baseline tumour burden is measured at the date of disease progression on nivolumab monotherapy.
Timepoint [4] 0 0
At 6 months during treatment.
Secondary outcome [5] 0 0
The number of patients alive at the end of the study, as assessed by date of death. - Overall survival (OS) is defined as the time between the date of registration to part 1 of the study and the date of death due to any cause.
Timepoint [5] 0 0
Through study completion, on average 5 years.
Secondary outcome [6] 0 0
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 [6] 0 0
From time of patient registration, until 30 days after the last dose of treatment.
Secondary outcome [7] 0 0
The number of participants with permanent discontinuation of treatment or delays due to toxicity, as assessed and graded according to CTCAE v4.03.
Timepoint [7] 0 0
From time of patient registration, until 30 days after the last dose of treatment.

Eligibility
Key inclusion criteria
1. Histologically confirmed unresectable, locally advanced (defined as disease not
amenable to curative surgery or radiation therapy) or metastatic nccRCC (both
treatment-naïve or those treated with a VEGFR TKI or another systemic medical
therapy). Non-clear cell histology including:

- Papillary renal cell carcinoma (type 1)

- Papillary renal cell carcinoma (type 2)

- Other: including chromophobe renal cell carcinoma, sarcomatoid renal cell
carcinoma, Xp11 translocation (TFE3+ IHC) carcinoma, other renal carcinoma NOS

2. Be =18 years of age on the day of signing informed consent

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

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

5. Adequate bone marrow function (should be performed within 14 days prior to
registration and with values within the ranges specified below):

- Haemoglobin = 90g/L

- Platelets = 100x109/L

- Neutrophil count = 1.5x109/L

6. Adequate liver function (should be performed 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 participants with known
Gilbert's syndrome who can have total bilirubin < 3.0 mg/dL

- AST or ALT = 3.0 x ULN (or = 5.0x ULN in the presence of liver metastases)

7. Adequate renal function (should be performed within 14 days prior to registration and
with values within the ranges specified below):

- Creatinine = 1.5x ULN OR

- Creatinine clearance (CrCl) = 30mL/min (use Cockcroft-Gault Formula)

8. Female participants of childbearing potential should have a negative urine or serum
pregnancy within 24 hours prior to registering the patient. If the urine test is
positive or cannot be confirmed as negative, a serum pregnancy test will be required.

9. Female participants of childbearing potential should be willing to use two methods of
birth control or be surgically sterile, or abstain from heterosexual activity for the
course of the study through 120 days after the last dose of study medication.
Participants of childbearing potential are those who have not been surgically
sterilized or have not been free from menses for > 1 year.

10. Male participants should agree to use an adequate method of contraception starting
with the first dose of study therapy through 120 days after the last dose of study
therapy.

11. Able to provide a formalin-fixed paraffin embedded (FFPE) tumour block, representative
of the participant's primary or metastatic disease (preferred), which must be
forwarded to the Centre for Biostatistics and Clinical Trials (BaCT) within 10 working
days post registration

12. 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

13. Has provided 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
1. Urothelial or transitional cell carcinoma of the renal pelvis or ureter

2. Predominant clear cell renal cell carcinoma. A minority of clear cell histology (<50%)
is acceptable, but there must be >50% non-clear cell histology predominant.

3. Participation in a study of an investigational agent within 30 days of registration.

4. Prior treatment with nivolumab, ipilimumab, 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 (NB Participant is eligible for
Part 2 of the study if they took nivolumab monotherapy in Part 1 of the study).

5. 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.

6. 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 registration. Intranasal, inhaled or
topical steroids are permitted in the absence of active autoimmune disease.
Participants are permitted to enrol if they have vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger.

7. Untreated brain or leptomeningeal metastases or current clinical or radiological
progression of known brain metastases or requirement for steroid therapy for brain
metastases. Participants with treated brain metastases are eligible if they have been
stable and off steroids for = 3 weeks.

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

9. Active infection requiring systemic therapy within 14 days before registration.

10. Receipt of live attenuated vaccination within 30 days of registration.

11. Life expectancy of less than 3 months.

12. Prior systemic therapy, surgery or radiation therapy within 4 weeks before
registration.

Note: If the participant has undergone major surgery, they must have recovered
adequately before registration.

13. History of another 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. Participants who have been free of other malignancies for
= 5 years prior to registration are eligible for this study.

14. Positive test for hepatitis B virus surface antigen (HBVsAg) or antibodies to
hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic
infection.

15. A history of other significant infection, including HIV. HIV testing is not mandatory
unless clinically indicated.

16. Participants should be excluded if they have a history of allergy to study drug
components, or a history of severe hypersensitivity reaction to any monoclonal
antibody.

17. Serious medical or psychiatric conditions that might limit the ability of the patient
to comply with the protocol

18. Female patient is pregnant or lactating.

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,SA,VIC
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment hospital [2] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [4] 0 0
St Vincents Hospital - Darlinghurst
Recruitment hospital [5] 0 0
Northern Cancer Institute - French Forest
Recruitment hospital [6] 0 0
St. George Hospital - Kogarah
Recruitment hospital [7] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [8] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [9] 0 0
Tamworth Hospital - North West Cancer Centre - Tamworth
Recruitment hospital [10] 0 0
Westmead Hospital - Westmead
Recruitment hospital [11] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [12] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [13] 0 0
Ashford Cancer Centre - Adelaide
Recruitment hospital [14] 0 0
Ballarat Oncology & Haematology Services - Ballarat
Recruitment hospital [15] 0 0
Box Hill Hospital - Eastern Health - Box Hill
Recruitment postcode(s) [1] 0 0
2460 - Albury
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
2086 - French Forest
Recruitment postcode(s) [6] 0 0
2217 - Kogarah
Recruitment postcode(s) [7] 0 0
2298 - Newcastle
Recruitment postcode(s) [8] 0 0
2031 - Randwick
Recruitment postcode(s) [9] 0 0
2340 - Tamworth
Recruitment postcode(s) [10] 0 0
2145 - Westmead
Recruitment postcode(s) [11] 0 0
4000 - Brisbane
Recruitment postcode(s) [12] 0 0
5000 - Adelaide
Recruitment postcode(s) [13] 0 0
5037 - Adelaide
Recruitment postcode(s) [14] 0 0
3355 - Ballarat
Recruitment postcode(s) [15] 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
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study aims to evaluate the safety, tolerability and effectiveness of new treatments for
kidney cancer called Nivolumab and Ipilimumab. The study is in two parts; in the first
instance patients receive nivolumab alone. If this treatment is not effective patients may
move onto the second part of the trial, where they receive nivolumab + ipilimumab. There is
no placebo.

The reason to offer one treatment alone, followed by two treatments together is that it is
thought that the double treatment may have more side-effects, but also may be effective in
people in whom the single first treatment (nivolumab alone) has not helped.

Nivolumab and ipilimumab are experimental treatments. This means that they are not an
approved treatment for non-clear cell kidney cancer in Australia.

The purpose of this study is to test the effectiveness, safety, and tolerability of Nivolumab
(also known as Opdivo or BMS-936558) and Ipilumumab (also known as MDX-010 or Yervoy).
Nivolumab and ipilimumab are antibodies (a type of human protein) that are being tested to
see if they will allow the body's immune system to work against tumour cells. The immune
system is the body's defence against cancer, bacteria and viruses. The effectiveness of
nivolumab and ipilimumab in cancer of the kidney will be assessed by measuring the size of
patient tumours via CT scans.

Nivolumab and ipilimumab have been used alone or in combination in many other cancers, and
are licenced for use in other cancers like advanced melanoma and bladder cancer in Australia.
They have not been tested in people with non-clear cell kidney cancer.

About 85 participants with non-clear cell kidney cancer are expected to participate in this
study, from Australia and New Zealand.

This research study has been initiated by Dr. Craig Gedye, is being conducted in
collaboration with the Centre for Biostatistics and Clinical Trials (BaCT) and sponsored in
Australia by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials
Group Pty Ltd. Bristol Myers Squibb (BMS) is supplying the study drugs and grant funding for
this research.
Trial website
https://clinicaltrials.gov/show/NCT03177239
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
Craig Gedye, MBBS, FRACP
Address 0 0
Country 0 0
Phone 0 0
+61 2 4014 3589
Fax 0 0
Email 0 0
craig.gedye@newcastle.edu.au
Contact person for scientific queries