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ANZUP - Non-clear Cell Post Immunotherapy CABozantinib (UNICAB) (UNICAB)

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ClinicalTrials.gov Identifier: NCT03685448
Recruitment Status : Not yet recruiting
First Posted : September 26, 2018
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Australian and New Zealand Urogenital and Prostate Cancer Trials Group

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


Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Papillary Renal Cell Carcinoma Type 1 Papillary Renal Cell Carcinoma Type 2 Chromophobe Renal Cell Carcinoma Sarcomatoid Renal Cell Carcinoma Xp11.2 Translocation-Related Renal Cell Carcinoma Drug: Cabozantinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Estimated Study Start Date : January 30, 2019
Estimated Primary Completion Date : January 30, 2022
Estimated Study Completion Date : January 30, 2024


Arm Intervention/treatment
Experimental: Experimental: Cabozantonib
Cabozantinib 60 mg/day, continuous dosing, taken orally.
Drug: 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).
Other Name: Cabometyx




Primary Outcome Measures :
  1. The objective response rate (ORR), as assessed by RECIST 1.1. [ Time Frame: Through study completion, on average 2 years. ]
    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.


Secondary Outcome Measures :
  1. The number of participants with adverse events that are related to study drug, as assessed and graded by CTCAE v5.0. [ Time Frame: From time of patient registration, until 30 days after the last dose of treatment. ]
  2. Progression-free survival (PFS), as assessed by RECIST1.1. [ Time Frame: Through study completion, on average 2 years. ]
  3. 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. [ Time Frame: Through study completion, on average 5 years. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03685448


Contacts
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Contact: Laura Galletta, BSc + 61 8559 7529 laura.galletta@petermac.org
Contact: Simran Chawla +61 2 8036 5271 simran.chawla@anzup.org.au

Locations
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Australia, New South Wales
Border Medical Oncology Research Unit / The Border Cancer Hospital Not yet recruiting
Albury, New South Wales, Australia, 2460
Contact: Craig Underhill       cunderhill@bordermedonc.com.au   
Contact: Jacqui McBurnie    +61 2 6064 1508    jacqui.mcburnie@bordermedonc.com.au   
Macquarie University Hospital Not yet recruiting
Macquarie Park, New South Wales, Australia, 2109
Contact: Howard Gurney       howard.gurney@mq.edu.au   
Contact: Radhika Butala    +61 2 9812 3561    radhika.butala@mq.edu.au   
Australia, South Australia
Flinders Medical Centre Not yet recruiting
Bedford Park, South Australia, Australia, 5042
Contact: Ganessan Kichenadasse       ganessan.kichenadasse@sa.gov.au   
Contact: Alison Richards       Alison.richards@sa.gov.au   
Adelaide Cancer Centre / Ashford Cancer Centre Research / Cancer Care SA
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Box Hill Hospital - Eastern Health Not yet recruiting
Box Hill, Victoria, Australia, 3128
Contact: Ian Davis       ian.davis@monash.edu   
Contact: Lauren Mitchell    +61 3 9094 9544    lauren.mitchell@monash.edu   
Sponsors and Collaborators
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Investigators
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Principal Investigator: David Pook, MBBS FRACPMD Australian & New Zealand Urogenital & Prostate Cancer Trials Group

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Responsible Party: Australian and New Zealand Urogenital and Prostate Cancer Trials Group
ClinicalTrials.gov Identifier: NCT03685448     History of Changes
Other Study ID Numbers: ANZUP1802
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases