CTRI/2025/11/097766 [Registered on: 20/11/2025] Trial Registered Prospectively
Last Modified On:
09/06/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Study to Compare Gastrointestinal Adverse Events of Two Cabozantinib Tablet Types in Adult patients With Advanced or Metastatic Kidney Cancer
Scientific Title of Study
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
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
AZ-08131-7300-004, Version: 1.0, 23/Apr/2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sandeep Singh
Designation
Vice President – Clinical Operations
Affiliation
CBCC Global Research
Address
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle
Ahmadabad GUJARAT 382210 India
Phone
09637555304
Fax
Email
sandeep.singh@cbccusa.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Singh
Designation
Vice President – Clinical Operations
Affiliation
CBCC Global Research
Address
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle
GUJARAT 382210 India
Phone
09637555304
Fax
Email
sandeep.singh@cbccusa.com
Details of Contact Person Public Query
Name
Dr Sandeep Singh
Designation
Vice President – Clinical Operations
Affiliation
CBCC Global Research
Address
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle
GUJARAT 382210 India
Phone
09637555304
Fax
Email
sandeep.singh@cbccusa.com
Source of Monetary or Material Support
Azurity Pharmaceuticals, Inc.
8 Cabot Road Suite 2000
Woburn, MA 01801
Tel No: 040-66079100
Primary Sponsor
Name
Azurity Pharmaceuticals, Inc.
Address
8 Cabot Road Suite 2000
Woburn, MA 01801
Tel No: 040-66079100
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
CBCC Global Research
TURQUOISE-IV 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle, Ahmedabad – 382210, Gujarat, India.
Room No 501, Department of Oncology
SPANV Medisearch Lifesciences Private Limited, 44, Parwana Bhawan, Kingsway,
Nagpur-44001, Maharashtra, India
Nagpur MAHARASHTRA
9373219772
drsaurabhprasad@gmail.com
Dr Bala Stalin Chowdary
Mahatma Gandhi Cancer Hospital & Research Institute
MOC Cancer care and Research Centre (Cellcure Cancer centre Pvt Ltd)
2nd floor Geras Imperium Oasis Morwadi, Pune, Maharashtra, India -411017 Pune MAHARASHTRA
7835826155
drnikhil@mocindia.co.in
Dr Kshitij Joshi
MOC Cancer Care and Research Centre,
Room No: NA, Department of Clinical Research, 1st Floor, SS House, Nehru Road, Navpada, Vile Parle, East Mumbai-400057,
Maharashtra, India
Mumbai (Suburban) MAHARASHTRA
9833662891
drkshitijjoshi@mocindia.co.in
Dr Anshul Agarwal
P P Maniya Hospital PVT LTD
OPD no. 5 Department of Oncology Opp. Dharuka College, Kapodra,Varachha Main Road, Surat-395006, Gujarat, India
Surat GUJARAT
9969465723
anshul.oncology@gmail.com
Dr Surender kumar Beniwal
S. P. Medical College and AG of Hospitals
Department of Oncology, RCC, S. P. Medical College and AG of Hospitals Bikaner RAJASTHAN
9414370484
beniwal.surendra@gmail.com
Dr Kalpeshkumar Keshavlal Prajapati
Shankus Hospital Pvt Ltd.
B/h Divine Child School, near Shankus Water Park, Ahmedabad- Mehsana Highway, Baliyasan, Mehsana, Gujarat- 382732 Mahesana GUJARAT
9909914228
drkkp23@gmail.com
Dr Ghanshyam Biswas
Sparsh Hospital and Critical care (P) Ltd.
A/407, Saheed Nagar, Bhubaneshwar, Khordha-Odisha-751007, India Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr Lokesh K N
SRV Agadi Hospital and Research Centre
#35, H. Siddaiah Road, Wilson Garden, Bengaluru-560027, Karnataka, India Bangalore KARNATAKA
8971609070
drlokeshsrv@gmail.com
Dr Arumugam Velappan
Tirunelveli Government Medical College and Hospital
North high ground, Palayamkottai, Tirunelveli, Tamil Nadu-627011, India Tirunelveli TAMIL NADU
Institutional Ethics Committee Erode Cancer Centre
Approved
Institutional Ethics Committee Tirunelveli Government Medical College and Hospital
Approved
Institutional Review Board, Mahatma Gandhi Cancer hospital - research institute
Approved
KIMS Kingsway Hospitals Ethics Committee
Approved
KMCRI ETHICS COMMITTEE
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Medstar Speciality Hospital Ethics Committee
Approved
Mumbai Oncocare Centre IEC
Approved
Mumbai Oncocare Centre Institutional Ethics Committee
Approved
Narsimha Saraswati Medical Foundation Ethics Committee
Approved
PP Maniya Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C649||Malignant neoplasm of unspecifiedkidney, except renal pelvis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Azurity Cabozantinib Tablets 39 mg
Note: If dose modification is required in the study, lower dose tablets of 26 mg and 13 mg strengths will be used.
Dosage: 39 mg, 26 mg and 13 mg
Route of Administration: Oral
Duration of Therapy: 84 Days
Frequency: Once daily for 84 Days
Comparator Agent
Cabometyx® 60 mg Filmtabletten Cabozantinib
Note: If dose modification is required in the study, lower dose tablets of 40 mg and 20 mg strengths will be used.
Dosage: 60 mg, 40 mg and 20 mg
Route of Administration: Oral
Duration of Therapy: 84 Days
Frequency: Once daily for 84 Days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1 Male and female subjects aged eighteen years or older 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 as per RECIST version 1.1.
3 Systemic therapy naïve subjects diagnosed with advanced or metastatic renal cell carcinoma and eligible to receive cabozantinib monotherapy (for example, subjects with intermediate or poor IMDC risk score).
OR
Subjects diagnosed with advanced or metastatic renal cell carcinoma who are eligible to receive cabozantinib monotherapy, irrespective of the line of treatment (for example, first, second, third, fourth, etc.) as per the treating investigator’s clinical judgment and standard of care. Eligible subjects must have radiographically documented progression of disease as per RECIST version 1.1 on or after treatment. Prior therapies may include:
a. Vascular Endothelial Growth Factor Receptor (VEGFR) targeting tyrosine kinase inhibitor such as sorafenib, sunitinib, axitinib, pazopanib, lenvatinib, or tivozanib as monotherapy or in combination (for example, axitinib with pembrolizumab or avelumab, lenvatinib with everolimus or pembrolizumab).
b. Cytokines such as interleukin two or interferon alfa.
c. Monoclonal antibodies as monotherapy (for example, bevacizumab, anti PD one) or in combination (for example, bevacizumab with everolimus or erlotinib, anti PD one with anti CTLA four).
d. Cytotoxic chemotherapy (for example, platinum based, gemcitabine with carboplatin or cisplatin, paclitaxel with carboplatin).
Please see Exclusion Criterion number two and number three.
4 For subjects who have received VEGFR targeting tyrosine kinase inhibitor, the following criteria must apply:
a Must have radiographically documented progression either during treatment or have been treated for at least four weeks and progressed within six months after the last dose. Radiographic progression is defined as per RECIST version 1.1.
b The last dose must have been within six months before the date of randomization.
5 Subjects who have achieved recovery to baseline or less than or equal to Grade One (as per 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 Zero (no diarrhea) is acceptable, as per CTCAE version 5.0.
6 Subjects with Karnofsky Performance Status score of seventy percent or higher.
7 Subjects with adequate organ and marrow function, based on meeting all of the following laboratory criteria within seven days before randomization:
a Absolute neutrophil count greater than or equal to one thousand five hundred per cubic millimeter.
b Platelets greater than or equal to one hundred thousand per cubic millimeter.
c Alanine aminotransferase and aspartate aminotransferase less than or equal to three times the upper limit of normal (for subjects with liver metastases, less than or equal to five times the upper limit of normal).
d Total bilirubin less than or equal to one and a half times the upper limit of normal (for subjects with Gilbert’s disease or liver metastases, less than or equal to three milligrams per deciliter or fifty one point three micromoles per liter).
e Hemoglobin A1c less than or equal to eight percent.
f Calculated creatinine clearance greater than or equal to thirty milliliters per minute (greater than or equal to zero point five milliliters per second) using the Cockcroft Gault equation.
g Electrolyte levels: serum calcium greater than or equal to eight point five milligrams per deciliter; magnesium greater than or equal to one point seven milligrams per deciliter; phosphorus greater than or equal to two point five milligrams per deciliter.
h Within normal limits or clinically non significant laboratory evaluation results for the coagulation parameters: prothrombin time, activated partial thromboplastin time, and international normalized ratio.
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 for at least four months after the last dose of study treatment.
Acceptable contraceptive measures include:
a Oral, parenteral, patch, or implant hormonal contraception.
b Intrauterine device or intrauterine system.
c Double barrier method of contraception (for example, condom and occlusive cap or condom and spermicidal agent).
d Male partner sterilization (at least six months prior to screening, should be the sole male partner for that subject).
e Female sterilization (surgical bilateral oophorectomy or tubal ligation) at least six 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 are defined as premenopausal females capable of becoming pregnant (that is, females who have had any evidence of menses in the past twelve months, except those who have had prior hysterectomy). However, women who have been amenorrheic for twelve or more months are still considered of childbearing potential if the amenorrhea may be due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression, or other reasons.
9 Female subjects will be considered of non childbearing potential if one of the following is documented in the medical history:
a Postmenopausal with spontaneous amenorrhea for at least one year, or spontaneous amenorrhea for less than one year with serum follicle stimulating hormone levels greater than forty milli international units per milliliter.
b Bilateral oophorectomy with or without hysterectomy and an absence of bleeding for at least six months before randomization.
c Total hysterectomy and an absence of bleeding for at least three months before randomization.
10 Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day One.
11 Male subjects whose partner is a female of childbearing potential must use effective birth control (for example, condom, vasectomy with confirmed absence of sperm, or sexual abstinence defined as refraining from heterosexual intercourse) during the study and for at least four months after the last dose.
12 Subjects who are able to understand and are willing to comply with all study requirements, including treatment (for example, able to swallow tablets), timing and or nature of required assessments, and completion of the subject diary.
13 Subjects with no history of addiction to any recreational drug or drug dependence or alcohol addiction.
ExclusionCriteria
Details
Subjects will be excluded from the study based on the following 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 twenty eight days prior to randomization.
4 Subjects who have received radiation therapy for bone metastasis within two weeks prior to randomization, or any other external radiation therapy within four 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, for example with radiotherapy or surgery, and neurologically stable for at least two weeks prior to randomization without the use of corticosteroids, or are on a stable or decreasing dose of ten milligrams daily prednisone, or equivalent.
6 Subjects diagnosed with another malignancy within two 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 twenty eight days prior to randomization.
8 Subjects with prior history of diarrhea greater than Grade 3 or colitis greater than or equal to Grade 3.
9 Subjects with arterial thrombotic events within six months prior to screening, including transient ischemic attack, cerebrovascular accident, peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the six months prior to screening, or myocardial infarction.
10 Subjects with clinically significant peripheral artery disease, that is, claudication on less than one block, or significant vascular disease, that is, aortic aneurysm or history of aortic dissection.
11 Subjects with a history of pulmonary embolism or untreated deep venous thrombosis within six months prior to screening. Note: Subjects with recent deep venous thrombosis who have been treated with therapeutic anticoagulation with low molecular weight heparin for at least six weeks are eligible at the discretion of the Principal Investigator and Sponsor.
12 Subjects who are receiving therapeutic warfarin greater than two milligrams per day. Note: Subjects on warfarin may be switched to low molecular weight heparin at the discretion of the Principal Investigator.
13 Subjects with ongoing need for a strong CYP3A4 inhibitor or inducer medication that cannot be switched to alternative treatment, or that are not candidates to receive cabozantinib at the study starting dose, for example, sixty milligrams Cabometyx tablets or thirty nine milligrams Azurity Cabozantinib tablets, prior to study entry.
14 Subjects with uncontrolled hypertension, that is, sustained systolic blood pressure greater than or equal to one hundred fifty millimeters of mercury and or diastolic blood pressure greater than or equal to ninety millimeters of mercury despite optimal antihypertensive treatment.
15 Subjects with congestive heart failure based on New York Heart Association class three or four.
16 Subjects with unstable cardiac arrhythmia within six months prior to screening.
17 During screening, subjects with corrected QT interval calculated by the Fridericia formula greater than four hundred eighty milliseconds.
18 Subjects with gastrointestinal disorders including those associated with a high risk of perforation or fistula formation and or sepsis:
a Tumors invading the gastrointestinal 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.
b Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra abdominal abscess within six months of screening. Complete healing of intra abdominal abscess must be confirmed before randomization.
19 Subjects with positive serology for Hepatitis B surface antigen and Hepatitis B core antibody, Hepatitis C Virus, or Human Immunodeficiency Virus.
Note: Subjects with a Hepatitis B core antibody positive result can be enrolled if a Hepatitis B surface antigen confirmatory negative test is obtained, suggestive of no active infection currently.
20 Subjects with uncompensated or symptomatic hypothyroidism.
21 Subjects with moderate to severe hepatic impairment, that is, 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, for example gastrointestinal surgery or removal or biopsy of brain metastasis, within two months of screening. Complete wound healing from major surgery must have occurred at least one month prior to randomization and from minor surgery, for example simple excision or tooth extraction, by at least two 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 thirty days prior to enrolment into the study, or have participated in a drug trial within four to five 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
On-site computer system
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To determine the incidence of diarrhea of any grade related to either Azurity Cabozantinib tablets or CABOMETYX (cabozantinib) tablets, as measured by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
To assess the percentage of subjects requiring dose reduction, interruptions, or treatment discontinuation due to adverse events.
From Day 1 (Baseline visit) to Day 84 (End of treatment)
Secondary Outcome
Outcome
TimePoints
To determine the incidence of acute, persistent, & chronic diarrhea following treatment with either Azurity Cabozantinib tablets or CABOMETYX® (cabozantinib) tablets.
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.
To assess the use of anti-diarrheal medications by grade of diarrhea by assigned treatment.
To assess the quantitative Functional Assessment of Chronic Illness Therapy- Diarrhea (FACIT-D) total score collected on day 1 & weekly intervals until the time of study completion.
To evaluate daily stool consistency as measured by the Bristol Stool Scale (BSS) collected from day 1 until study completion.
From Day 1 (Baseline visit) to Day 84 (End of treatment)
Target Sample Size
Total Sample Size="45" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a 2-part, randomized,
parallel, multi-center, phase 2/3 study to assess the gastrointestinal (GI) safety
of Azurity Cabozantinib tablets versus CABOMETYX® (cabozantinib) tablets, as a
single agent, in adult patients with advanced or metastatic renal cell
carcinoma.
The
study consists of two unique clinical investigations.
Part 1 –
Randomized, Open-label, Phase 2 Study planned to be conducted in India and
Australia.
Part 2 –
Randomized, Double-blind, Phase 3 Study. This part of the study will be
global, and will utilize double-dummy placebo. A formal protocol amendment
will be made prior to initiation of Part 2 (Phase 3) of study.
Part 1: Phase 2 Study
Approximately 45 subjects are
planned to be randomized, with an allocation ratio of 2:1, to Azurity
Cabozantinib tablets 39 mg (n=30) or CABOMETYX® (cabozantinib) tablets 60 mg
(n=15) for a duration of 12 weeks.
The Phase 2 study analysis will
be performed after completion of Part 1 (Phase 2) of the study, to determine if
the investigation will continue onto Part 2 (Phase 3 investigation). If the
results support continuation, a formal sample size estimation to support Part 2
(Phase 3) of the study will be conducted. The analysis of Part 2 will be
considered separate from Part 1. A formal protocol amendment will be made prior
to initiation of Part 2 of the study.