Recruiting PHASE2 Locally Advanced Renal Cell Carcinoma

New treatment option for Locally Advanced Renal Cell Carcinoma

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?

Zanzalintinib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for locally advanced renal cell carcinoma.

Also referred to as XL092.

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: All subjects will receive zanzalintinib 100mg orally (PO) once daily plus nivolumab standard of care dosing (i.e., 240mg IV every 2 weeks or 480mg IV every 4 weeks) for a total of 12 weeks, followed by restaging scan/evaluation for surgical operability and an adaptive approach that includes (1) surgical resection if the participant is eligible for surgery (Cohort A), (2) up to 48 weeks total (from Cycle 1 Day 1) of zanzalintinib plus nivolumab if the participant has partial response or stable disease but remains inoperable (Cohort B1), or (3) stopping protocol mandated treatment to receive standard of care systemic therapy and continue follow up per protocol if the participant has disease progression (Cohort B2).

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...
Locally advanced (cT3/T4, N0-1) OR deemed surgically challenging/inoperable per surgeon discretion. Satisfying either of the criteria allows for...

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. NOTE: prior surgery and/or radiation to other areas of the...
Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). NOTE: For...
Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).

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. NOTE: HIPAA authorization may be included in the...
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. NOTE: biopsy should be performed at least 5 days before...
Locally advanced (cT3/T4, N0-1) OR deemed surgically challenging/inoperable per surgeon discretion. Satisfying either of the criteria allows for enrollment. NOTE: Surgically challenging/inoperable per surgeon discretion...
cT4 disease
N1 disease
Surgery may be significantly complex and/or significantly affect residual renal function, where neoadjuvant therapy may downsize/downstage primary tumor for maximum renal preservation, including:
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...
Adequate organ and marrow function, based upon meeting all the following laboratory criteria within 30 days before first dose of study treatment:
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. If a urine test is done and it is positive or cannot be confirmed as negative, a serum pregnancy...
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. Males able to...
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...
Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). NOTE: For prohibited anticoagulants, people must have discontinued the...
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.
The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
Unstable or deteriorating cardiovascular disorders:
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
Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
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. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study...
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); (2) CD4+ T cell count...
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. Minor surgery (eg...
QTc calculated by the Fridericia formula \> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment. NOTE: Triplicate ECG evaluations will be performed at screening and the average of...
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's taking place

St Louis, Missouri, United States
Dallas, Texas, United States
Richmond, Virginia, United States

Compensation & support

A stipend or compensation may be offered.

Compensation mentioned.

ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.

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 - 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 - 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?

Study sites include St Louis, Missouri, United States; Dallas, Texas, United States; Richmond, Virginia, United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.