CTRI/2025/11/097766RecruitingPhase 2
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
Azurity Pharmaceuticals, Inc.13 sites in 1 country45 target enrollmentStarted: December 1, 2025Last updated:
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 45
- Locations
- 13
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Masking
- None
Eligibility Criteria
- Ages
- 18.00 Year(s) to 65.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •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.
- •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).
- •Cytokines such as interleukin two or interferon alfa.
- •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).
- •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.
- •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.
- •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).
- •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.
- •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.
- •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.
Exclusion Criteria
- •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
- •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.
- •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.
- •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.
- •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.
Investigators
Dr Sandeep Singh
CBCC Global Research
Study Sites (13)
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