Lenvatinib and Pembrolizumab Before Surgery for the Treatment of Locally Advanced Non-Metastatic Kidney Cancer

  • STATUS
    Recruiting
  • End date
    Aug 5, 2024
  • participants needed
    17
  • sponsor
    Emory University
Updated on 22 March 2022
cancer
monoclonal antibodies
carcinoma
anticoagulants
glomerular filtration rate
metastasis
neutrophil count
tumor cells
pembrolizumab
metastatic renal cell carcinoma

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 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.

Description

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.

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.

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.

After completion of study treatment, patients are followed up within 14 days, then every 12 weeks thereafter.

Details
Condition Kidney Cancer, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8
Treatment questionnaire administration, quality-of-life assessment, Pembrolizumab, Lenvatinib, Lenvatinib Mesylate
Clinical Study IdentifierNCT04393350
SponsorEmory University
Last Modified on22 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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 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 (specimens must be collected within 72 hours prior to the start of study treatment)
Platelets >= 100 000/uL (specimens must be collected within 72 hours prior to the start of study treatment)
Hemoglobin >= 9.0 g/dL (specimens must be collected within 72 hours prior to the start of study treatment) or ≥5.6 mmol/La
Renal
Creatinine =≤1.5 × ULN OR Measured or calculatedb creatinine clearance (GFR can also be
used in place of creatinine or CrCl)=≥30 mL/min for participant with creatinine levels >1.5
× institutional ULN
Creatinine clearance (CrCl) calculated per the Cockcroft and Gault formula
Hepatic
Total bilirubin=≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin
levels >1.5 × ULN AST (SGOT) and ALT (SGPT)=≤2.5 × ULN (≤5 × ULN for participants with
liver metastases)
Coagulation
International normalized ratio (INR) OR prothrombin time (PT) Activated partial
thromboplastin time (aPTT)=≤1.5 × ULN unless participant is receiving anticoagulant therapy
as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST
(SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular
filtration rate; ULN=upper limit of normal
Criteria must be met without erythropoietin dependency and without packed red blood
cell (pRBC) transfusion within last 2 weeks
Creatinine clearance (CrCl) should be calculated per institutional standard
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 (specimens must be collected within 72
hours prior to the start of study treatment)
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 (specimens must be collected within 72 hours
prior to the start of study treatment)
Serum 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]) >= 40 mL/min (>= 0.67 mL/sec) for participant with
creatinine levels > 1.5 x institutional ULN (specimens must be collected within
hours prior to the start of study treatment)
Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with
total bilirubin levels > 1.5 x ULN (specimens must be collected within 72 hours
prior to the start of study treatment)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
(=< 5 x ULN for participants with liver metastases) (specimens must be collected
within 72 hours prior to the start of study treatment)
All females must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin
[beta-hCG]) at the screening visit and the baseline visit. A pregnancy test needs
to be performed within 72 hours of the first dose of study drug. Women of
childbearing potential (WOCBP) must agree to use a highly effective method of
contraception for the entire study period and for 120 days after study
discontinuation
Male subjects who are partners of women of childbearing potential must use a
condom and their female partners of childbearing potential must use a highly
effective method of contraception beginning at least 1 menstrual cycle prior to
starting study drugs, throughout the entire study period, and for 120 days after
the last dose of study drug, unless the male subjects are totally sexually
abstinent or have undergone a successful vasectomy with confirmed azoospermia or
unless the female partners have been sterilized surgically or are otherwise
proven sterile

Exclusion Criteria

Evidence of metastatic disease on pre-treatment imaging
Cardiovascular disorders
Serious non-healing wound/ulcer/bone fracture
Has an active infection requiring systemic therapy
The subject has received of any type of cytotoxic, biologic or other systemic
anticancer therapy for kidney cancer
The subject has received any other type of investigational agent within 28 days before
the first dose of study treatment
Excluding the primary tumor leading to enrollment in this study, any other active
malignancy (except for localized prostate cancer, definitively treated melanoma
in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the
bladder or cervix) within the past 24 months
Prior treatment with lenvatinib or any agent directed against PD-1, PD-L1 or PD-L2, or
another stimulatory or co inhibitory T-cell receptor (e.g. CTLA-4, OX 40, CD137)
Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment
Subjects having > 1+ proteinuria on urinalysis will undergo 24-hour urine collection
for quantitative assessment of proteinuria. Subjects with urine protein >= 1 g/24-hour
will be ineligible
Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition
that might affect the absorption of lenvatinib
The subject has uncontrolled, significant intercurrent or recent illness including
but not limited to, the following conditions
New York Heart Association congestive heart failure of grade II or above
unstable angina, myocardial infarction within the past 6 months, or serious
cardiac arrhythmia associated with significant cardiovascular impairment
within the past 6 months
Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm
Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive
treatment
Prolongation of corrected QT (QTc) interval to > 480 msec per
electrocardiogram (ECG) within 28 days before first dose of study treatment
Clinically significant hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of
red blood, or other history of significant bleeding (e.g. pulmonary hemorrhage)
within 3 weeks prior to the first dose of study drug
History of organ allograft (subject has had an allogenic tissue/solid organ
transplant)
Biologic response modifiers (e.g. granulocyte colony-stimulating factor) within 4
weeks before study entry. Chronic erythropoietin therapy is permitted provided that no
dose adjustments were made within 2 months before first dose of study treatment
Subjects must have recovered adequately from any toxicity and/or complications from
major surgery prior to starting therapy
Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study drug. Examples of live vaccines include, but are not limited to, the
following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever
rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however
intranasal influenza vaccines (e.g. FluMist are live attenuated vaccines and are not
allowed
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
Has a known history of active Hepatitis B (e.g., hepatitis B surface antigen [HBsAg])
or hepatitis C (e.g., HCV RNA qualitative is detected)
Has uncontrolled HIV defined by a CD4+ count < 350 cells/uL, an AIDS-defining
opportunistic infection within the last 12 months prior to study enrollment or
documented multidrug resistance that prevents effective HIV therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
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