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EUCTR2016-000916-14

A Clinical Trial to Compare How Well Lenvatinib Works in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in Patients with Kidney Cancer that has Spread and Who Have Not Previously Been Treated With Anti-Cancer Medicines

Datenbasis: WHO (Import vom 26.01.2020)
Geändert: 15.12.2019
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Advanced Renal Cell Carcinoma
MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) ;Therapeutic area: Diseases [C] - Cancer [C04]

Interventions (Datenquelle: WHO)


Trade Name: Kisplyx 4 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lenvatinib
CAS Number: 417716-92-8
Current Sponsor code: E7080
Other descriptive name: LENVATINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Kisplyx 10 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: lenvatinib
CAS Number: 417716-92-8
Current Sponsor code: E7080
Other descriptive name: LENVATINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Afinitor 5 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: pembrolizumab 100 mg/4 mL (25 mg/mL)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Sutent 12.5 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SUNITINIB
CAS Number: 557795-19-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Trade Name: Sutent 25 mg
Pharmaceutical Form: Capsule, hard
INN or Propose

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
1. Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable).
2. Documented evidence of advanced RCC.
3. At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:
• Lymph node (LN) lesion that measures at least 1 dimension as =1.5 cm in the short axis
• Non-nodal lesion that measures =1.0 cm in the longest diameter
•The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion.
4. Male or female subjects age =18 years (or any age greater than 18 years if that age is considered to be an adult per the local jurisdiction) at the time of informed consent
5. Karnofsky Performance Status (KPS) of =70.
6. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mmHg at Screening and no change in antihypertensive medications within 1 week before the Cycle 1/Day 1.
7. Adequate renal function as creatinine =1.5× upper limit of normal(ULN); or for subjects with creatinine >1.5×ULN, the calculated creatinine clearance =30 mL/min (per the Cockcroft-Gault formula) is acceptable.
8.Adequate bone marrow function defined by:
•Absolute neutrophil count (ANC) =1500/mm3
•Platelets =100,000/mm3
•Hemoglobin =9 g/dL
NOTE: Criteria must be met without erythropoietin dependency and
without packed red blood cell (pRBC) transfusion within the previous 2weeks.
9.Adequate blood coagulation function defined by International
Normalized ratio (INR) =1.5 unless participant is receiving anticoagulant
therapy, as long as INR is within therapeutic range of intended use of
anticoagulants.
10.Adequate liver function defined by:
•Total bilirubin =1.5×ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
•Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and
aspartate aminotransferase (AST) =3×ULN (in the case of liver
metastases =5×ULN), unless there are bone metastases. Subjects with
ALP values >3×ULN and known to have bone metastases can be included.
11. Provide written informed consent.
12. Willing and able to comply with all aspects of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 580
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 470

Exclusion criteria:
1.Subjects who have received any systemic anticancer therapy for RCC,ancluding anti-VEGF therapy, or any systemicinvestigational anticancer agent.Prior adjuvant treatment with an investigational anticancer agent is not allowed unless investigator can provide evidence of subject's randomization to placebo arm. 2. Subjects with CNS metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatm.3. Active malignancy (except for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past 24 months. Subjects with history of localized & low risk prostate cancer are allowed in the study if they were treated with curative intent and there is no PSA recurrence within the past 5 yrs.
4.Prior radiation therapy within 21 days prior to start of study treatment with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 w.prior to study treatmentstart.5.Subjects who are using other investigational agents or who had received invest.drugs =4 w. prior to study treatm. start.6.Received a live vaccine within 30 days of planned start of studytreatm. (Cycle 1/Day 1).Examples of live vaccines include, measles,mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies,Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonalinfluenza vaccines for injection are generally killed virus vaccines andare allowed; however, intranasal influenza vaccines (eg, FluMist®) arelive attenuated vaccines and are not allowed.
7.Subj. with proteinuria >1+ on urine dipstick testing will undergo 24-h urine collection for quantitative assess. of proteinuria. Subj. with urine protein =1 g/24 h will be ineligible
8.Fasting total cholesterol >300 mg/dL (or >7.75 mmol/L) and/or fasting triglycerides level >2.5 x ULN. Note:these subjects can be included after initiation or adjustment of lipid-lowering medication.
9.Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: these subjects can be included after initiation or adjustment of glucose-lowering medication.10.Prolongation of QTc interval to >480 ms.11.Subjects who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.12. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib, everolimus, and/or sunitinib.13.Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (eg, carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.14. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug.15Significant cardiovascular impairment within 12 months of the firstdose of study drug: history of congestive heart failure greater than NewYork Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascula

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000916-14

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2016-000916-14-PL

Weitere Informationen zur Studie

Registrationsdatum der Studie

29.03.2017

Einschluss der ersten teilnehmenden Person

20.04.2017

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects with Advanced Renal Cell Carcinoma (CLEAR) - CLEAR

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)


Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
Number of treatment arms in the trial: 3

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

Main Objective: The primary objective of the study is to demonstrate that lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) is superior compared to sunitinib alone (Arm C) in improving progression-free survival (PFS) (by independent imaging review [IIR] using Response Evaluation Criteria In Solid Tumors [RECIST 1.1]) as first-line treatment in subjects with advanced renal cell carcinoma (RCC).;
Secondary Objective: •To compare objective response rate (ORR) of subjects treated with lenvatinib in combination with everolimus or pembrolizumab versus sunitinib.
•To compare overall survival (OS) of subjects treated with lenvatinib in combination with everolimus or pembrolizumab versus sunitinib.
•To compare safety and tolerability of treatment with lenvatinib in combination with everolimus or pembrolizumab versus sunitinib.
•To compare the impact of treatment on Health-Related Quality of Life
•To assess PFS on next-line of therapy (PFS2)
• To assess PFS based on investigator assessment per RECIST v.1.1
• To characterize the population pharmacokinetics (PK) of lenvatinib when co-administered with everolimus or pembrolizumab.
• To characterize the population PK of everolimus and pembrolizumab when co-administered with lenvatinib.
• To assess the PK/pharmacodynamic relationship between exposure and efficacy/biomarkers/safety.
;Primary end point(s): • Progression-free survival (PFS) by independent review is defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurs first) as determined by IIR using RECIST 1.1. PFS censoring rules will follow the FDA guidance of 2007; specifics of this will be detailed in the Statistical Analysis Plan.;Timepoint(s) of evaluation of this end point: The primary PFS analysis will be performed when a total of at least 551 PFS events (as determined by IIR) are observed among the 3 treatment arms. Assuming an enrolment rate of 37 subjects per month, a final analysis of PFS will occur approximately 43 months (29 months enrolment period and 14 months follow up period) after first subject is randomized.

Sekundäre Endpunkte (Datenquelle: WHO)

Timepoint(s) of evaluation of this end point: As per primary endpoint. ;
Secondary end point(s): • Objective response rate (ORR) is defined as the proportion of subjects who have best overall response of CR or PR as determined by IIR using RECIST 1.1.
• Overall survival (OS) is defined as the time from the date of randomization to the date of death from any cause. Subjects who are lost to follow-up and those who are alive at the date of data cut-off will be censored at the date the subject was last known alive, or date of data cut-off, whichever occurs first.
• Safety will be assessed summarizing the incidence of treatment-emergent adverse events (TEAEs) and SAEs together with all other safety parameters.
• Proportion of subjects who discontinued treatment due to toxicity is defined as the proportion of subjects who discontinue study treatment due to treatment-emergent adverse events (TEAEs).
• Time to treatment failure due to toxicity is defined as the time from the date of randomization to the date that a subject discontinues study treatment due to TEAEs.
• Health-Related Quality of Life (HRQoL) will be assessed using the Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS), the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and the European Quality of Life (EuroQOL) EQ-5D-3L instruments.
• PFS on next-line of therapy (PFS2) is defined as the time from randomization to disease progression on next-line of treatment, or death from any cause, (whichever occurs first).
• Progression-free survival (PFS) by investigator assessment is defined as the time from the date of randomization to the date of first documentation of disease progression based on the investigator assessment per RECIST v.1.1 or death (whichever occurs first).
• Model-predicted clearance and AUC for lenvatinib in Arms A and B.
• Model-predicted clearance and AUC for everolimus in Arm A, and pembrolizumab in Arm B.

Kontakt für Auskünfte (Datenquelle: WHO)

Eisai Ltd.

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Australia, Austria, Belgium, Canada, Czech Republic, Greece, Ireland, Japan, Korea, Netherlands, Poland, Republic of, Russian Federation, Spain, Switzerland, United Kingdom, United States

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

EU Medical Information
Mosquito Way
Eisai Europe Ltd.
4402086001400
EUmedinfo@eisai.net

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

EU Medical Information
Mosquito Way
Eisai Europe Ltd.
4402086001400
EUmedinfo@eisai.net

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Eisai Ltd.

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

E7080-G000-307;NCT02811861;2016-000916-14-GB