Clinical trial for Infiltrating Bladder Urothelial Carcinoma With Squamous Differentiation
Official title Cabozantinib in Combination With Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Cancer
ClinicalTrials.gov ID: NCT04878029
What this study is testing
What is Cabozantinib S-malate?
Cabozantinib S-malate is an investigational medicine, being studied as a potential treatment for infiltrating bladder urothelial carcinoma with squamous differentiation.
Also referred to as BMS-907351, Cabometyx.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study is testing whether a mix of cabozantinib and enfortumab vedotin is safe. It also looks at how well the mix works in advanced bladder cancer.
- Who it's for
- You may join if you have bladder cancer that has spread locally or to other parts of body.
- What's involved
- You would take cabozantinib pills and get enfortumab vedotin infusions. You will have doctor visits and tests to check safety and how well it works.
- Time commitment
- The study lasts several months with regular clinic visits and follow‑up checks.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Histologically-documented urothelial carcinoma (squamous differentiation or mixed cell types allowed if urothelial carcinoma is present)
- Metastatic disease or unresectable locally-advanced disease
- Must have received prior treatment with a checkpoint inhibitor (CPI).
- Must either have prior treatment with platinum-containing chemotherapy or be ineligible at time of enrollment
- Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments...
You likely can't join if
- Prior treatment with cabozantinib
- Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs)
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study...
- Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study...
- Radiation therapy within 2 weeks before first dose of study treatment.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for...
See the full eligibility criteria
Who can join
- Histologically-documented urothelial carcinoma (squamous differentiation or mixed cell types allowed if urothelial carcinoma is present)
- Metastatic disease or unresectable locally-advanced disease
- Must have received prior treatment with a checkpoint inhibitor (CPI). A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor alone or with any other combination
- Must either have prior treatment with platinum-containing chemotherapy or be ineligible at time of enrollment
- Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive...
- Tumor tissue samples must be available for submission prior to initiation of study treatment or patient must be willing to undergo repeat tumor biopsy
- Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)
- An Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2
- Must be \>= 18 years of age
- Absolute neutrophil count (ANC) \>= 1500/uL without granulocyte colony-stimulating factor support (within 28 days before first dose of study treatment)
- White blood cell count \>= 2500/uL (within 28 days before first dose of study treatment)
- Platelets \>= 100,000/uL without transfusion (within 28 days before first dose of study treatment)
- Hemoglobin \>= 9 g/dL (within 28 days before first dose of study treatment)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =\< 3 x upper limit of normal (ULN).
- Total bilirubin =\< 1.5 x ULN (for people with Gilbert's disease =\< 3 x ULN) (within 28 days before first dose of study treatment)
- Prothrombin (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial...
- Calculated creatinine clearance \>= 30 mL/min (\>= 0.5 mL/sec) using the Cockcroft-Gault equation (within 28 days before first dose of study treatment)
- Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol), or 24-hour (h) urine protein =\< 1 g (within 28 days before first dose of study treatment)
- Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
- Sexually active fertile people and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the...
- Female people of childbearing potential must not be pregnant at screening. Female people are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization...
What rules you out
- Prior treatment with cabozantinib
- Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs)
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment
- Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 2 weeks before first dose of study treatment
- Radiation therapy within 2 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after...
- Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
- Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in people without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week...
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
- Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose of...
- people with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep venous thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted...
- The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute...
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment.
- Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment
- Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose of study...
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
- Lesions invading or encasing any major blood vessels
- Ongoing sensory or motor neuropathy grade \>= 2
- Other clinically significant disorders that would preclude safe study participation.
- Serious non-healing wound/ulcer/bone fracture.
- Uncompensated/symptomatic hypothyroidism.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
- Uncontrolled diabetes mellitus defined as a hemoglobin A1C \>= 8%
- Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment.
- Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment.
- Pregnant or lactating females
- Inability to swallow tablets
- Previously identified allergy or hypersensitivity to components of the study treatment formulations
- Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable...
The study team makes the final eligibility decision.
Where it is enrolling
- Atlanta, Georgia, United States
Compensation & support
A stipend or payment for your time may be offered.
No amount is published here because ClinicalTrials.gov has no reliable field for payment or travel support. Ask the study team what's actually covered (payment for your time, travel, parking, or other study costs), and never join a trial for the compensation alone.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team, so confirm the details with them.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Atlanta, Georgia, United States. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.