Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12625001422415
Ethics application status
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Approved
Date submitted
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11/11/2025
Date registered
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17/12/2025
Date last updated
Help: Date last updated
17/04/2026
Date data sharing statement initially provided
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17/12/2025
Type of registration
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Prospectively registered

Titles & IDs
Public title
Safety Study to Evaluate Gastrointestinal Adverse Events of Azurity Cabozantinib Tablets vs. CABOMETYX® Tablets in Advanced or Metastatic Renal Cell Carcinoma Patients
Scientific title
A Phase 2/3 Randomized, Parallel, Multicenter, Safety Study to Evaluate Gastrointestinal Adverse Events of Azurity Cabozantinib Tablets vs. CABOMETYX® (cabozantinib) Tablets as a Single-Agent in Adult Patients with Advanced or Metastatic Renal Cell Carcinoma
Additional trial identifiers [1] 315553 0
AZ-08131-7300-004
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Gastrointestinal Discomfort 339173 0
Metastatic renal cell carcinoma 339840 0
Condition category
Condition code
Cancer 335452 335452 0 0
Kidney
Oral and Gastrointestinal 336076 336076 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
In Arm 1, participants will receive Azurity Cabozantinib tablets (International Non-proprietary Name: Cabozantinib) administered orally at a dose of 39 mg once daily for 12 weeks. The tablets are available in 39 mg, 26 mg, and 13 mg strengths to allow for dose modification if required. The product is manufactured by Cdymax (India) Pharma Private Limited, Bengaluru, India. Doses will be taken on an empty stomach, with fasting (except for water) maintained for at least 2 hours before and 1 hour after administration. Tablets are to be swallowed whole and not crushed. The first dose (Day 1) will be administered under supervision at the study site to assess initial tolerability, with subsequent doses self-administered at home at approximately the same time each day. Participants will be provided with a diary to record daily dosing details, any episodes of diarrhoea (including number and consistency of stools as per the Bristol Stool Scale), and the use of any concomitant medications such as anti-diarrhoeals or anti-emetics. Site staff will review diaries and returned medication at each study visit to assess compliance. Health-related quality of life will be evaluated weekly using the FACIT-D questionnaire, administered in person during site visits and by telephone in alternate weeks. If toxicity-related dose adjustments are required, reduced doses of 26 mg or 13 mg tablets will be used according to the protocol. Dose modifications will be determined according to the protocol’s toxicity management guidelines. If a participant experiences adverse events attributable to cabozantinib, supportive care measures will be initiated at the earliest signs of toxicity. If supportive care is insufficient to control symptoms, the Principal Investigator may implement dose interruption or reduction. A maximum of two dose reductions is permitted; further reduction results in permanent discontinuation of cabozantinib . Dose reductions follow a predefined sequence using the available 26 mg and 13 mg tablet strengths . The assigned starting dose cannot be increased once reduced, and participants whose dosing is held for 2 weeks will be discontinued after medical assessment and discussion with the sponsor . Dose modification decisions are made at the discretion of the Investigator based on toxicity severity, tolerability, and CTCAE v5.0 grading of adverse events, including guideline-based management of diarrhea and other cabozantinib-related toxicities .
Intervention code [1] 332181 0
Treatment: Drugs
Description of the comparator or control
In Arm 2, participants will receive the comparator product CABOMETYX® tablets (International Non-proprietary Name: Cabozantinib) administered orally at a dose of 60 mg once daily for 12 weeks. CABOMETYX® tablets are film-coated and available in 60 mg, 40 mg, and 20 mg strengths to allow for dose modification if necessary. The product is manufactured by Ipsen Pharma, France. Administration instructions are identical to those of the test product: tablets are to be swallowed whole under fasting conditions, with fasting maintained for at least 2 hours before and 1 hour after dosing. Dosing, monitoring, diary completion, and adherence assessments follow the same procedures as for the test arm. Dose modifications for CABOMETYX® will be implemented according to the protocol’s predefined toxicity management procedures. If a participant experiences adverse events considered related to cabozantinib, supportive care will be provided at the earliest signs of toxicity. If toxicity persists despite supportive measures, the Principal Investigator may interrupt treatment or reduce the dose. A maximum of two dose reductions is permitted; if a further reduction would be required, CABOMETYX® treatment will be permanently discontinued. Dose reductions follow the protocol-defined sequence using the available 40 mg and 20 mg tablet strengths. The starting dose cannot be increased once reduced, and participants whose dosing is held for 2 weeks will be discontinued following medical assessment and discussion with the sponsor. Decisions regarding dose modification are based on severity and tolerability of adverse events, including grading according to CTCAE v5.0 and guideline-based management of diarrhea and other cabozantinib-related toxicities.
Control group
Active

Outcomes
Primary outcome [1] 343459 0
To determine the incidence of diarrhea of any grade related to either Azurity Cabozantinib tablets or CABOMETYX® (cabozantinib) tablets
Timepoint [1] 343459 0
Daily from Day 1 of drug administration until End of Treatment (EOT) at Week 12
Primary outcome [2] 343460 0
To assess the percentage of subjects requiring dose reduction, interruptions, or treatment discontinuation due to adverse events - composite outcome
Timepoint [2] 343460 0
Daily from Day 1 of drug administration until End of Treatment (EOT) at Week 12
Secondary outcome [1] 454478 0
To determine the incidence of acute, persistent, and chronic diarrhea following treatment with either Azurity Cabozantinib tablets or CABOMETYX® (cabozantinib) tablets - composite outcome
Timepoint [1] 454478 0
Daily from Day 1 of drug administration until End of Treatment (EOT) at Week 12
Secondary outcome [2] 454479 0
To determine the time to the onset of the first event of diarrhea of any grade, defined as the number of days from day 1 of dosing with either Azurity Cabozantinib tablets or CABOMETYX® (cabozantinib) tablets until the first episode of diarrhea classified as Grade 1 or higher occurs.
Timepoint [2] 454479 0
Continuously from Day 1 of drug administration until End of Treatment (EOT) at Week 12
Secondary outcome [3] 454480 0
To assess the use of anti-diarrheal medications by grade of diarrhea by assigned treatment.
Timepoint [3] 454480 0
Continuously from Day 1 of drug administration until study completion (Week 14).
Secondary outcome [4] 454481 0
To assess the quantitative Functional Assessment of Chronic Illness
Timepoint [4] 454481 0
Baseline (Day 1) and weekly thereafter till week 12
Secondary outcome [5] 454482 0
To evaluate daily stool consistency
Timepoint [5] 454482 0
Daily from Day 1 (baseline) until study completion (week 14).
Secondary outcome [6] 454483 0
To assess the incidence of treatment emergent serious adverse events (SAEs) during the study, its frequency, severity, pattern and causal relationship to the IP - composite outcome
Timepoint [6] 454483 0
Continuously from screening (week -1 before intervention commencement) through Week 14 (End of Study)

Eligibility
Key inclusion criteria
1. Male and female subjects aged more than or equal to 18 years on the day of consent, with a documented histological or cytological diagnosis of advanced or metastatic renal cell carcinoma.
2. Subjects with evaluable or measurable disease per RECIST 1.1.
3. Systemic therapy-naïve subjects diagnosed with advanced or metastatic renal cell carcinoma and eligible to receive cabozantinib monotherapy (e.g., intermediate or poor IMDC risk score).
OR
Subjects diagnosed with advanced or metastatic renal cell carcinoma that are eligible to receive cabozantinib monotherapy, irrespective of the line of treatment (e.g., 1st, 2nd, 3rd, 4th, etc.) it may constitute, as per treating investigator’s clinical judgement and standard of care. Eligible subjects must have radiographically documented progression of disease, as per RECIST 1.1, on or after treatment. Prior therapies may include:
a. Vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitor (TKI) (i.e., sorafenib, sunitinib, axitinib, pazopanib lenvatinib, or tivozanib) as monotherapy or as a combination regimen (e.g., axitinib with pembrolizumab or avelumab, lenvatinib with everolimus or pembrolizumab),
b. Cytokines (i.e., interleukin-2, interferon-alfa)
c. Monoclonal antibodies as monotherapy (i.e., bevacizumab, anti-PD-1) or in combination (e.g., bevacizumab with everolimus or erlotinib, anti-PD-1 with anti-CTLA-4)
d. Cytotoxic chemotherapy (e.g., platinum based, gemcitabine with carboplatin or cisplatin, paclitaxel with carboplatin).
Please see Exclusion Criterion #2 and #3.
4. For subjects who have received VEGFR-targeting TKI, the following criteria must apply:
a. Must have radiographically documented progression either during treatment or been treated for at least 4 weeks and progressed within 6 months after the last dose. Radiographic progression is defined as per RECIST 1.1.
b. The last dose must have been within 6 months before the date of randomization.
5. Subjects who have achieved recovery to baseline or more than or equal to Grade 1 CTCAE version 5.0 from toxicities related to any prior treatments, unless adverse events are not clinically significant and/or stable on supportive therapy.
Note: For diarrhea only grade 0 (no diarrhea) is acceptable, per CTCAE version 5.0
6. Subjects with Karnofsky Performance Status (KPS) score of more than or equal to 70%..
7. Subjects with adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 7 days before randomization:
a. Absolute neutrophil count (ANC): more than or equal to 1500/mm3.
b. Platelets: more than or equal to 100,000/mm3.
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): less than or equal to 3.0 × upper limit of normal (ULN); [For subjects with liver metastases: less than or equal to 5 x ULN].
d. Total bilirubin: less than or equal to 1.5 X ULN; [For subjects with Gilbert’s disease or liver metastases, less than or equal to 3 mg/dL (less than or equal to 51.3 µmol/L).]
e. HbA1c: equal to 8%.
f. Calculated creatinine clearance: more than or equal to 30 mL/min (more than or equal to 0.5 mL/sec) using the Cockroft-Gault equation.
g. Electrolyte levels: serum calcium more than or equal to 8.5 mg/dL; magnesium more than or equal to 1.7 mg/dL; phosphorus more than or equal to 2.5 mg/dL
h. Within normal limits or clinically non-significant laboratory evaluation results for the coagulation parameters: PT, aPTT and INR
8. If a subject is female, she shall be: a) of non-childbearing potential or b) of childbearing potential practicing at-least two acceptable methods of contraception during the study and should use an effective form of birth control during study and for at least 4 months after the last dose of study treatment.
Acceptable contraceptive measures are:
a. Oral, parenteral, patch, or implant hormonal contraception
b. Intrauterine device (IUD) or intrauterine system (IUS)
c. Double barrier method of contraception (condom and occlusive cap or condom and spermicidal agent)
d. Male partner sterilization (at least 6 months prior to screening, should be the sole male partner for that subject)
e. Female sterilization (surgical bilateral oophorectomy) or tubal ligation at least 6 weeks prior to study participation
f. Total abstinence from heterosexual intercourse as part of routine lifestyle; partial abstinence is not acceptable
Note: Female subjects of childbearing potential (FOCBP) are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
9. Female subject will be considered of ‘non-childbearing’ potential if one of the following is reported and documented on the medical history:
a. Postmenopausal with spontaneous amenorrhea for at least one year, or spontaneous amenorrhea for less than one (less than 1) year with serum FSH levels more than 40mIU/ml, or
b. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months before randomization, or
c. Total hysterectomy and an absence of bleeding for at least 3 months before randomization.
10. Female subjects of childbearing potential with negative serum pregnancy test at screening and negative urine pregnancy test at Day 1.
11. Male subjects whose partner is a FOCBP, should use effective birth control (e.g., condom, vasectomy with confirmed absence of sperm, sexual abstinence defined as refraining from heterosexual intercourse) during study and for at least 4 months after the last dose.
12. Subjects who are able to understand, and are willing to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments and will complete the subject diary.
13. Subjects with no history of addiction to any recreational drug or drug dependence or alcohol addiction.
14. Subject with left ventricular ejection fraction (LVEF) more than or equal to 50% by an echocardiogram during screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. Subjects with known hypersensitivity to cabozantinib or to any of the excipients of the formulation.
2. Subjects who have received prior treatment with cabozantinib (including as an investigational product from participation in a previous clinical trial).
3. Subjects who have received any type of small molecule kinase inhibitor (including an investigational kinase inhibitor) or cytokine or chemotherapy or anticancer antibody (including an investigational antibody) within 28 days prior to randomization.
4. Subjects who have received radiation therapy for bone metastasis within 2 weeks prior to randomization, or any other external radiation therapy within 4 weeks before randomization. Subjects with clinically relevant ongoing complications from radiation therapy are also not eligible for enrolment in the study.
5. Subjects with active brain metastases, or carcinomatous meningitis or cranial epidural disease unless adequately treated (e.g., radiotherapy and/or surgery, etc.) and neurologically stable for at least 2 weeks prior to randomization without the use of corticosteroids or are on a stable or decreasing dose of less than or equal to 10 mg daily prednisone (or equivalent).
6. Subjects diagnosed with another malignancy within 2 years before randomization, except for superficial skin cancers, or localized low grade tumors deemed cured and not treated with systemic therapy.
7. Subjects with serious non-healing wounds, ulcers, or bone fractures, requiring intervention within 28 days prior to randomization.
8. Subjects with prior history of diarrhea more than Grade 3 or colitis more than or equal to Grade 3.
9. Subjects with arterial thrombotic events within 6 months prior to screening including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the 6 months prior to screening, or myocardial infarction (MI).
10. Subjects with clinically significant peripheral artery disease (i.e., claudication on less than one block) or significant vascular disease (i.e., aortic aneurysm, history of aortic dissection).
11. Subjects with a history of pulmonary embolism or untreated deep venous thrombosis (DVT) within 6 months prior to screening. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulation with low molecular weight heparin for at least 6 weeks are eligible at the discretion of the PI and Sponsor.
12. Subjects who are receiving therapeutic warfarin (more than 2 mg/day). Note: Subjects on warfarin may be switched to low molecular weight heparin at the discretion of the PI.
13. Subjects with ongoing need for a strong CYP3A4 inhibitors/inducer medication that cannot be switched to alternative treatment or that are not candidates to receive Cabozantinib at the study starting dose (e.g., 60 mg CABOMETYX® (cabozantinib) tablets or 39 mg Azurity Cabozantinib tablets) prior to study entry.
14. Subjects with uncontrolled hypertension (i.e., sustained systolic blood pressure more than or equal to 150 mmHg and/or diastolic blood pressure more than or equal to 90 mmHg despite optimal antihypertensive treatment).
15. Subjects with congestive heart failure based on New York Heart Association class 3 or 4.
16. Subjects with unstable cardiac arrhythmia within 6 months prior to screening.
17. During screening, subjects with corrected QT interval calculated by the Fridericia formula (QTcF) more than 480 msec.
18. Subjects with GI disorders including those associated with a high risk of perforation or fistula formation and/or sepsis:
a. Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, toxic megacolon, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction, or presence of an intestinal ostomy.
b. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months of screening. Complete healing of intra-abdominal abscess must be confirmed before randomization.
19. Subjects with positive serology for Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV).
Note: Subjects with Hepatitis B core antibody (HBcAb) positive result can be enrolled if a confirmatory negative test is obtained suggestive of no active infection currently
20. Subjects with uncompensated/symptomatic hypothyroidism.
21. Subjects with moderate to severe hepatic impairment (i.e., Child-Pugh B or C).
22. Subjects with known malabsorption syndrome.
23. Subjects requiring hemodialysis or peritoneal dialysis.
24. Subjects with a history of solid organ transplantation.
25. Subjects who had major surgery (i.e., GI surgery, removal or biopsy of brain metastasis) within 2 months of screening. Complete wound healing from major surgery must have occurred at least 1 month prior to randomization and from minor surgery (i.e., simple excision, tooth extraction) by at least 2 weeks before randomization.
26. Pregnant or lactating women, or female subjects unwilling to use any form of contraception during the study.
27. Subjects participating in any other clinical study within 30 days prior to enrolment into the study or have participated in a drug trial within 4 to 5 half-lives of the drug being tested, whichever was longer, prior to enrolment into the study.
28. Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results, which in the Investigator’s opinion, would be likely to interfere with the subject’s capacity to provide informed consent, with the subject’s participation in the study, or with the interpretation of the results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2026
Actual
Date of last participant enrolment
Anticipated
1/12/2026
Actual
Date of last data collection
Anticipated
9/03/2027
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 27592 0
India
State/province [1] 27592 0

Funding & Sponsors
Funding source category [1] 320151 0
Commercial sector/Industry
Name [1] 320151 0
Azurity Pharmaceuticals, Inc.
Country [1] 320151 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Azurity Pharmaceuticals, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 322716 0
Commercial sector/Industry
Name [1] 322716 0
Azurity Pharmaceuticals India LLP.
Address [1] 322716 0
Country [1] 322716 0
India
Secondary sponsor category [2] 323130 0
Commercial sector/Industry
Name [2] 323130 0
Ingenu CRO Pty Ltd
Address [2] 323130 0
Country [2] 323130 0
Australia
Other collaborator category [1] 283752 0
Commercial sector/Industry
Name [1] 283752 0
CBCC Global Research
Address [1] 283752 0
Country [1] 283752 0
India

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318697 0
Bellberry Human Research Ethics Committee B
Ethics committee address [1] 318697 0
Ethics committee country [1] 318697 0
Australia
Date submitted for ethics approval [1] 318697 0
11/06/2025
Approval date [1] 318697 0
09/10/2025
Ethics approval number [1] 318697 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 144978 0
Dr Sem Liew
Address 144978 0
Vitalis Clinical Research, 456 St Kilda Rd, Melbourne VIC 3004
Country 144978 0
Australia
Phone 144978 0
+61 0387260628
Fax 144978 0
Email 144978 0
[email protected]
Contact person for public queries
Name 144979 0
Darryl Davies
Address 144979 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 144979 0
Australia
Phone 144979 0
+61 1300 030 380
Fax 144979 0
Email 144979 0
[email protected]
Contact person for scientific queries
Name 144980 0
Erin Owusu
Address 144980 0
Azurity Pharmaceuticals, Inc., 8 Cabot Road Suite 2000 Woburn, MA 01801
Country 144980 0
United States of America
Phone 144980 0
+1 877 495 6858
Fax 144980 0
Email 144980 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.