Locally Advanced Renal Cell Carcinoma study: Zanzalintinib vs Nivolumab
Official title Neoadjuvant Zanzalintinib Plus Nivolumab in Patients With Locally Advanced and/or Inoperable Clear Cell Renal Cell Carcinoma With or Without Non-measurable Metastasis
ClinicalTrials.gov ID: NCT06794229
What this study is testing
What is Zanzalintinib (XL092)?
An investigational oral medicine being studied for locally advanced renal cell carcinoma.
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
- The study wants to see if giving zanzalintinib and nivolumab for 12 weeks can shrink tumors enough to allow surgery or improve treatment options.
- Who it's for
- It is looking for adults with locally advanced kidney cancer that may not be able to have surgery right now.
- What's involved
- Participants will take 100 mg of zanzalintinib by mouth every day and receive nivolumab by IV infusion every 2 or 4 weeks for 12 weeks. After that, doctors will check if the tumor can be removed or decide on further treatment.
- Time commitment
- The initial treatment lasts 12 weeks, followed by a scan and a decision about surgery or more therapy. The total study period can be up to 48 weeks depending on the patient’s response.
- Phase 2: a mid-size study of how well it works
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
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information...
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 within 30 days prior to registration.
- Histologically confirmed (i.e., tissue from primary kidney tumor of interest) diagnosis of clear cell renal cell carcinoma with or without...
- cT4 disease
You likely can't join if
- Non-clear cell histology.
- Measurable metastatic disease per RECIST 1.1 criteria and other non-measurable lesions including bone metastasis, leptomeningeal disease...
- Prior systemic therapy, including zanzalintinib, nivolumab and other vascular endothelial growth factor receptor-tyrosine kinase inhibitors...
- Prior surgery and/or radiation to the primary renal cell carcinoma tumor of interest.
- 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...
See the full eligibility criteria
Who can join
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 within 30 days prior to registration.
- Histologically confirmed (i.e., tissue from primary kidney tumor of interest) diagnosis of clear cell renal cell carcinoma with or without sarcomatoid features.
- cT4 disease
- N1 disease
- IVC tumor thrombus involvement
- cT1-3 tumor with pre-surgery calculated creatinine clearance \<60 mL/min per Cockcroft-Gault formula OR solitary kidney (any calculated creatinine clearance), with potential to convert from radical to partial nephrectomy
- High complexity on RENAL Nephrometry Score (score ≥ 10)
- Other reversible comorbidity(ies) that in the opinion of the surgeon renders the patient surgically challenging/inoperable at baseline, where neoadjuvant therapy and medical optimization may allow subsequent surgery
- Non-measurable soft tissue metastasis with longest diameter \< 10mm or pathological lymph nodes \< 15 mm in short axis are allowed.
- Recovery to baseline or Grade ≤ 1 severity (CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological...
- Platelets (Plt): ≥ 100,000 /mm3; without transfusion within 2 weeks of screening laboratory sample collection
- Absolute Neutrophil Count (ANC): ≥ 1500 K/mm3; without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection
- Hemoglobin (Hgb): ≥ 9 g/dL; without transfusion within 2 weeks of screening laboratory sample collection
- Creatinine OR Calculated creatinine clearance: ≤ 1.5 x ULN OR ≥ 40 mL/min
- Urine protein-to-creatinine ratio (UPCR): ≤ 1.5 mg/mg (≤ 169.8 mg/mmol) creatinine
- Total bilirubin: ≤ 1.5 × upper limit of normal (ULN); for people with Gilbert's disease ≤ 3 x ULN
- Aspartate aminotransferase (AST): ≤ 3× ULN
- Alanine aminotransferase (ALT): ≤ 3 × ULN
- Alkaline Phosphatase (ALP): ≤ 3 × ULN
- Females of childbearing potential must have a negative urine or serum pregnancy test within 48 hours of Cycle 1 Day 1.
- Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or must use an effective method(s) of contraception.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
What rules you out
- Non-clear cell histology.
- Measurable metastatic disease per RECIST 1.1 criteria and other non-measurable lesions including bone metastasis, leptomeningeal disease, lymphangitic involvement of lung or skin, pathologically confirmed-malignant...
- Prior systemic therapy, including zanzalintinib, nivolumab and other vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs)/immune checkpoint inhibitors(IOs), for the treatment of renal cell...
- Prior surgery and/or radiation to the primary renal cell carcinoma tumor of interest. NOTE: prior surgery and/or radiation to other areas of the kidney (i.e., prior small kidney tumor resection or radiation) is allowed...
- 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...
- Use of any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
- Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades...
- 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, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment
- Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA/TIA arterial thromboembolic events within 3 months before to first dose of study treatment NOTE: people with a...
- Prior history of myocarditis
- Tumors invading the GI-tract from external viscera
- Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis
- Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
- Known gastric or esophageal varices
- Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks
- Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study...
- Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed).
- Lesions invading a major blood vessel. NOTE: people with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior vena cava) are eligible.
- Active infection requiring systemic treatment. NOTE: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed.
- Known infection with acute or chronic hepatitis B or C.
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. NOTE: people meeting all the following criteria: (1) on stable anti-retroviral therapy (ART)
- Serious non-healing wound/ulcer/bone fracture.
- Malabsorption syndrome.
- Pharmacologically uncompensated, symptomatic hypothyroidism.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
- Requirement for hemodialysis or peritoneal dialysis.
- History of solid organ or allogeneic stem cell transplant.
- Major surgery (as defined in Appendix A) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (ie nephrectomy) within 4 weeks prior to first dose of study treatment.
- QTc calculated by the Fridericia formula \> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment.
- History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
- Pregnant or lactating females.
- Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to study treatment within 2 years before first dose of study...
- Other conditions, which in the opinion of the Investigator, would compromise the safety of the subject or the subject's ability to complete the study.
- Any active, known or suspected autoimmune disease. NOTE: people with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring...
- Known positive test for tuberculosis infection if supported by clinical or radiographic evidence of disease.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography...
- Known free thyroxine (FT4) outside the laboratory normal reference range. Asymptomatic people with FT4 abnormalities can be eligible after sponsor-investigator approval.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy (\> 10 mg daily prednisone equivalent) or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.
- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
The study team makes the final eligibility decision.
Where it is enrolling
- St Louis, Missouri, United States
- Dallas, Texas, United States
- Richmond, Virginia, 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 St Louis, Missouri, United States; Dallas, Texas, United States; Richmond, Virginia, 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.