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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03685448




Registration number
NCT03685448
Ethics application status
Date submitted
25/09/2018
Date registered
26/09/2018
Date last updated
18/06/2019

Titles & IDs
Public title
ANZUP - Non-clear Cell Post Immunotherapy CABozantinib (UNICAB)
Scientific title
A Phase II of Single Agent Cabozantinib in Patients With Locally Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma Post Immunotherapy or Who Are Unsuitable for Immunotherapy (ANZUP1802)
Secondary ID [1] 0 0
ANZUP1802
Universal Trial Number (UTN)
Trial acronym
UNICAB
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
Xp11.2 Translocation-Related Renal Cell 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 - Cabozantinib

Experimental: Experimental: Cabozantonib - Cabozantinib 60 mg/day, continuous dosing, taken orally.


Treatment: Drugs: Cabozantinib
The 20 mg cabozantinib drug product is a film-coated, white, round, immediate-release tablet. Cabozantinib should not be stored above 25°C (77°F).

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

Outcomes
Primary outcome [1] 0 0
The objective response rate (ORR), as assessed by RECIST 1.1. - 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 2 years.
Secondary outcome [1] 0 0
The number of participants with adverse events that are related to study drug, as assessed and graded by CTCAE v5.0.
Timepoint [1] 0 0
From time of patient registration, until 30 days after the last dose of treatment.
Secondary outcome [2] 0 0
Progression-free survival (PFS), as assessed by RECIST1.1.
Timepoint [2] 0 0
Through study completion, on average 2 years.
Secondary outcome [3] 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 [3] 0 0
Through study completion, on average 5 years.

Eligibility
Key inclusion criteria
- Histologically confirmed un-resectable, locally advanced (defined as disease not
amenable to curative surgery or radiation therapy) or metastatic non-clear cell renal
cell histology (comprising greater than 50% of the tumour) including:

1. Papillary renal cell carcinoma (type 1)

2. Papillary renal cell carcinoma (type 2)

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

- Patient is either;

1. Ineligible for checkpoint inhibitor immunotherapy due to pre-existing autoimmune
disorder in the opinion of the investigator, or

2. Has progressed following treatment with checkpoint inhibitor immunotherapy

- Be greater than 18 years of age on the day of signing informed consent

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

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (refer to Appendix
1)

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

1. Haemoglobin = 90g/L

2. Platelets = 100x109/L

3. Neutrophil count = 1.5x109/L

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

1. 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

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

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

1. Creatinine = 1.5x ULN, or

2. Creatinine clearance (CrCl) = 30mL/min (use Cockcroft-Gault Formula, refer to
Appendix 2)

3. Urine protein-to-creatinine ratio (UPCR) = 1 mg/mg (= 113.2 mg/mmol) creatinine
or 24-hour urine protein <1 g.

- Negative pregnancy test for female participants of childbearing potential within 72
hours prior to registration. If urine test cannot be confirmed as negative, a negative
serum pregnancy test is required.

- Female participants of childbearing potential must 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 greater than 1 year.

- Male participants with sexual partners of childbearing age must 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.

- 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 (if not previously collected for the UNISoN study).

- 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

- 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
- Patients with urothelial or transitional cell carcinoma of the renal pelvis or ureter

- 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.

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

- 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 metastases have
been shown to be stable on repeat imaging post treatment and steroid treatment has
been ceased for = 3 weeks.

- Serious Cardiovascular disorders:

1. Congestive heart failure New York Heart Association class 3 or 4, unstable angina
pectoris, serious cardiac arrhythmias.

2. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100
mm Hg diastolic despite optimal antihypertensive treatment.

3. Stroke (including TIA), myocardial infarction, or other ischemic event, or
thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6
months before randomization.

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

- Life expectancy of less than 3 months.

- Prior systemic therapy, surgery or radiation therapy within 4 weeks before
registation. Note: If the participant has undergone major surgery, complete wound
healing must have occurred 1 month prior to registration. Patients must not have
received prior targeted therapy or chemotherapy, but may have received previous
checkpoint immunotherapy, for example, via the UNISoN trial (NCT03177239)

- History of another active malignancy 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 treated for other malignancies and have a <5% chance of
relapse according to the investigator are eligible for this study.

- Active hepatitis B virus infection indicated by positive Hepatitis B surface antigen
(HBVsAg) or active Hepatitis C infection indicated by antibodies to hepatitis C virus
ribonucleic acid (HCV antibody). Patients with undetectable viral load indicating cure
in the presence of HBVsAg or HCV antibodies are eligible.

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

- 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.

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

- Patient is pregnant or breastfeeding.

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
Open (masking not 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 Research Unit / The Border Cancer Hospital - Albury
Recruitment hospital [2] 0 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 0 0
St George Hospital - Kogarah
Recruitment hospital [4] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [5] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [6] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [7] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [8] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [9] 0 0
Adelaide Cancer Centre / Ashford Cancer Centre Research / Cancer Care SA - Kurralta Park
Recruitment hospital [10] 0 0
Box Hill Hospital - Eastern Health - Box Hill
Recruitment hospital [11] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
2460 - Albury
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
- Kogarah
Recruitment postcode(s) [4] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [5] 0 0
- Newcastle
Recruitment postcode(s) [6] 0 0
- St Leonards
Recruitment postcode(s) [7] 0 0
- Herston
Recruitment postcode(s) [8] 0 0
5042 - Bedford Park
Recruitment postcode(s) [9] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [10] 0 0
3128 - Box Hill
Recruitment postcode(s) [11] 0 0
- Clayton

Funding & Sponsors
Primary sponsor type
Other
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Renal cell carcinoma (RCC) is the 9th most common cancer in Australia, the 10th most common
cancer in Western populations.~75% of kidney cancers are clear-cell renal cell carcinomas
(ccRCC). Many patients present with advanced or unresectable disease at diagnosis and a
number of treatments are now available for metastatic ccRCC included vascular endothelial
growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs), mTOR inhibitors, and
cytokines. More recently first line use of immunotherapy demonstrated improved survival with
checkpoint inhibitors. While many patients benefit from first-line treatment, progression is
inevitable and these treatments remain on the whole palliative. Second-line VEGFR TKIs, mTOR
inhibitors and immunotherapy have some benefit but in a smaller increment than first-line
treatment.

While ~75% of kidney cancers are the clear-cell variant, ~25% of kidney cancers are non-clear
cell histology (nccRCC) and include papillary, chromophobe, sarcomatoid, collecting duct
carcinoma, Xp11 translocation carcinoma and unclassified. Patients with non-ccRCC have
significantly lower response rates and poorer median progression-free survival and overall
survival than those with ccRCC. Non clear cell histologies have largely been excluded from
large phase III randomised clinical trials and therefore the optimal treatment and sequencing
of therapies for these patients remains unclear.

Despite recent unprecedented advances in treatment, there continues to be an unmet need to
improve outcomes for patients with previously untreated, unresectable or metastatic renal
cell carcinoma. This is particularly relevant in non-clear cell RCC. Because it is a rarer
subtype of metastatic renal cell carcinoma, it is more challenging to study, and treatment
efficacy data is sparse.

The research project is testing a new treatment for participants with locally advanced or
metastatic non-clear cell kidney cancer. The new treatment involves a drug called
Cabozantinib (also known as Cabometyx). This drug has been used previously in many cancers,
including clear cell kidney cancer and thyroid cancer.

The purpose of this study is to test the effectiveness (how well the drug works), safety, and
tolerability of Cabozantinib. Cabozantinib is a anti-cancer drug that works by blocking
cancer cell growth. It blocks particular proteins called protein kinases on cancer cells.
Protein kinases encourage the cancer to grow. Cabozantinib is called a multi kinase inhibitor
because it blocks a number of these proteins. How well cabozantinib works in cancer of the
kidney will be tested by measuring the change in size of your tumours that are seen on CT
scans.

Cabozantinib is approved to treat clear cell kidney cancer and thyroid cancer in Australia.
It has not been tested in people with non-clear cell kidney cancer.

About 48 participants with non-clear cell kidney cancer are expected to participate in this
study, from Australia. Even though this study may be suitable for you, it is possible that
you may not be enrolled in this study.

This research study has been initiated by Dr. David Pook, 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.
Ipsen is supplying
Trial website
https://clinicaltrials.gov/show/NCT03685448
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Pook, MBBS FRACPMD
Address 0 0
Australian & New Zealand Urogenital & Prostate Cancer Trials Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Laura Galletta, BSc
Address 0 0
Country 0 0
Phone 0 0
+ 61 8559 7529
Fax 0 0
Email 0 0
laura.galletta@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03685448