Lenvatinib and Pembrolizumab before Surgery for the Treatment of Locally Advanced Non-Metastatic Kidney Cancer
Kidney Cancer
Unknown Primary
18 Years and older, Male and Female
Winship4955-20 (primary)
NCI-2020-01064
Summary
This phase II trial studies how well lenvatinib and pembrolizumab before surgery work in treating patients with kidney cancer that has spread from its original site of growth to nearby tissues or lymph nodes (locally advanced) but has not spread to other places in the body (non-metastatic). Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lenvatinib and pembrolizumab before surgery may kill more tumor cells.
Objectives
PRIMARY OBJECTIVE:
I. To assess the objective response rate (complete and partial responses), following the administration of lenvatinib and pembrolizumab for a total of 4 cycles (12 weeks) in patients with locally-advanced, biopsy-proven non-metastatic clear cell renal cell carcinoma (ccRCC) prior to undergoing nephrectomy (partial or radical).
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of neoadjuvant lenvatinib plus pembrolizumab in a presurgical population as well as the safety of adjuvant pembrolizumab post-surgery.
II. To determine the clinical outcomes including disease-free survival (DFS) and overall survival (OS) of patients with non-metastatic ccRCC treated with neoadjuvant lenvatinib and pembrolizumab and adjuvant pembrolizumab.
III. To evaluate surgery-related complications and outcomes as per the Clavien-Dindo classification system.
EXPLORATORY OBJECTIVES:
I. To evaluate changes in biomarkers of immune activation and gene expression before, during and after treatment.
II. To assess the quality of life, frailty and sarcopenia of patients before and after treatment.
OUTLINE:
Patients receive lenvatinib orally (PO) once daily (QD) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatments repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 7 days after completion of cycle 4, patients undergo kidney surgery. Beginning 4-12 weeks after completion of surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, magnetic resonance imaging (MRI), computed tomography (CT) and multigated acquisition scan (MUGA) or echocardiography throughout study.
After completion of study treatment, patients are followed up within 14 days, then every 12 weeks thereafter.
Eligibility
- Patients with a renal mass consistent with a clinical stage >= T3Nx or TanyN+ or deemed unresectable by surgeon
- Renal cell carcinoma with clear cell component on pre-treatment biopsy of the primary tumor
- The subject is = 18 years of age on the day of signing informed consent
- The participant (or legally acceptable representative if applicable) provides written informed consent and the willingness and ability to comply with all aspects of the protocol
- Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- Absolute neutrophil count (ANC) >= 1500/uL
- Platelets >= 100 000/uL
- Hemoglobin >= 9.0 g/dL >= 5.6 mmol/L
* Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
- Creatinine =< 1.5 x ULN OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN
* Creatinine clearance (CrCl) should be calculated per institutional standard
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases)
- International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x upper limit of normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies:
* Not a woman of childbearing potential (WOCBP) OR
* A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment
- A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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