A Phase III, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination With Cabozantinib Versus Cabozantinib Alone in Patients With Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma Who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment

CompletadoFase 3ClinicalTrials.gov

ID: NCT04338269Tipo: INTERVENTIONALInicio: 28 de jul de 2020Fin estimado: 24 de mar de 2025

Traducción no disponible, mostrando original

Resumen

This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically confirmed locally advanced or metastatic clear cell or non-clear cell (papillary, chromophobe, and unclassified only) RCC. RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation.
Radiographic disease progression to prior ICI therapy for RCC. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. ICI is defined by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab, or nivolumab. Only patients for whom the immediate preceding line of therapy was an ICI are allowed.
Measurable disease per RECIST v1.1
Evaluable IMDC risk score
Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible. Both archival and fresh samples are preferred.
KPS score of \>=70
Recovery to baseline or Grade \</= 1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable in the opinion of the investigator. Grade 2 alopecia is allowed for study participation
Adequate hematologic and end-organ function
Negative HIV test at screening
Negative hepatitis B testing at screening
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Criterios de exclusión

History of leptomeningeal disease
Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
Patients received cabozantinib at any time prior to screening
Patients who received more than one ICI treatment in the locally advanced or metastatic setting
Patients who received more than two prior lines of therapy in the locally advanced or metastatic setting
Patients who have received a mammalian target of rapamycin (mTOR) inhibitor in any setting
Symptomatic, untreated, or actively progressing CNS metastases
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
History of malignancy other than renal carcinoma within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1
Active tuberculosis
Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after final dose of atezolizumab and 4 months after final dose of cabozantinib
Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety
Pharmacologically uncompensated, symptomatic hypothyroidism
Uncontrolled hypertension defined as sustained blood pressure \>150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment (all countries except France); sustained BP \> 140 mmHg systolic or \> 90 mmHg diastolic despite optimal antihypertensive treatment (France only)
Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, unstable arrhythmia, or unstable angina) within 3 months prior to initiation of study treatment
Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1
History of congenital QT syndrome
History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g. clopidogrel)

Intervenciones

drug

Atezolizumab

Atezolizumab 1200 mg will be administered at a fixed dose on Day 1 of each 21-day cycle by IV infusion every 3 weeks.

drug

Cabozantinib

Cabozantinib 60 mg (three 20-mg tablets) administered orally once daily.

Ubicaciones

Fundación CENIT para la Investigación en Neurociencias

Buenos Aires, Argentina

Inst. Alexander Fleming

Buenos Aires, Argentina

Hospital Britanico

Ciudad Autonoma Bs As, Argentina

Centro Medico Austral OMI

Ciudad Autonoma Buenos Aires, Argentina

Patrocinadores

PrincipalHoffmann-La Roche

ColaboradorExelixis

ColaboradorChugai Pharmaceutical

Aviso: La información de este ensayo proviene de fuentes públicas y tiene carácter exclusivamente informativo. No constituye asesoramiento médico, regulatorio ni de ningún otro tipo. Las traducciones son automatizadas y no poseen validez oficial. Consultá siempre con un profesional de la salud. Ver Términos de Uso.

A Phase III, Multicenter, Randomized, Open-Label Study to... | EligiMed