Health Condition 1: C649- Malignant neoplasm of unspecifiedkidney, except renal pelvis
Conditions
Interventions
Intervention1: 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
R
Sponsors
Azurity Pharmaceuticals, Inc.
CBCC Global Research
Eligibility
Inclusion criteria
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 1.1. 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 investigatorâ??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 Gilbertâ??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 p
Exclusion criteria
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 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 ant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. Timepoint: From Day 1 (Baseline visit) to Day 84 (End of treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. Timepoint: From Day 1 (Baseline visit) to Day 84 (End of treatment) | — |
Countries
Australia, India
Contacts
Public ContactDr Sandeep Singh
CBCC Global Research
Outcome results
None listed