This is a multicenter, open-label, non-randomized, single arm, 2 parts, phase II clinical trial evaluating the efficacy and safety of pembrolizumab and lenvatinib plus standard of care chemotherapy (with carboplatin and etoposide ) in subjects with histologically confirmed extensive-stage small-cell lung cancer who have not previously received systemic therapy for this malignancy.
A total of 85 subjects will be assigned to study treatment with pembrolizumab + lenvatinib + chemotherapy. Positive tumor programmed cell death-ligand 1 (PD-L1) expression will not be required for enrollment; however, subjects' tumors will be screened for PD-L1 expression. The primary endpoint for the Part 1 is to determine the safety of the combination. The primary endpoint for Part 2 is to determine the Progression Free survival (PFS) using RECIST 1.1. assessed by investigator. The sponsor estimates that the trial will require approximately 4 years from the time the first participant signs the informed consent until the last participant's last study-related telephone call or visit (2 years recruiting patients, 1 year of treatment and at least 1 year of follow up)
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Lenvatinib is an oral, potent multiple receptor tyrosine kinase (RTK) i that selectively inhibits VEGF-driven VEGFR2 phosphorylation and suppressed proliferation and tube formation in human umbilical vein endothelial cell models. Antitumor activity of lenvatinib in vivo has been shown in numerous xenograft animals. These results suggest that lenvatinib may be a novel anticancer therapy through inhibition of angiogenesis and may be useful as either monotherapy or in combination with other anticancer drugs. Part 1 (safety run-in) and Part 2: The study intervention consists of: Dose: 8 mg (induction) and 20 mg (maintenance) Dose Frequency: Once daily Dose formulation: Capsule Route of administration: Oral Treatment duration: 4 cycles (induction) and no treatment duration limit (maintenance).
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Part 1 (safety run-in) and Part 2: Dose: 200 mg Frequency: Day 1, Q3W Route: Intravenous Treatment Period: Up to 35 cycles or until reaching a discontinuation criterion
ICO Badalona, Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
RECRUITINGPart 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of lenvatinib 8 mg to be used in combination with pembrolizumab plus chemotherapy
Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0 criteria.
Time frame: From the subject's written consent to participate in the study through 90 days after the final administration of the drug
Part 2:To assess the efficacy of the treatment in terms of the Progression Free Survival (PFS)
PFS is defined as the time from enrollment to the date of the first documentation of disease progression, as determined by investigator per RECIST 1.1, or death from any cause, whichever is earlier.
Time frame: From the date of the end of induction treatment until 12 months
Part 1 (for patients treated at part 2): Objective response per RECIST 1.1 based on investigator
Objective response is a confirmed complete response (CR) or partial response (PR), as determined by investigator per RECIST 1.1.
Time frame: From the date of the end of treatment until 12 months
Part 1 (for patients treated at part 2): Duration of Response (DOR) per RECIST 1.1 based on investigator
DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause (whichever is earlier), for participants who demonstrate a confirmed CR or PR. Response will be determined by BICR per RECIST 1.1.
Time frame: From date of documentation of tumor response until date of first documented progression, assessed up to 12 months
Part 1 (for patients treated at part 2): Overall Survival
OS is defined as the time from enrollment to the date of death from any cause.
Time frame: From the date of the end of treatment until 12 months
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Standard first-line treatment for the vast majority of patients with SCLC, regardless of stage, involves combination chemotherapy with etoposide plus cisplatin or carboplatin. Pharmacotherapeutic group: Cytostatics, plant alkaloids and other natural products, derived from podophyllotoxin. Mechanism of action :The main effect of etoposide appears to be in the late S and early G2 phase of the cell cycle, in mammalian cells. Part 1 (safety run-in) and Part 2: Dose: 100 mg/m2 Frequency: Day 1-3, Q3W Route: Intravenous Treatment Period: 4 cycles
Pharmacotherapeutic group: Other antineoplastic agents, platinum compounds. Carboplatin, like cisplatin, binds to DNA to produce inter- and intra-strand cross-links cells exposed to carboplatin. DNA reactivity has been linked to cytotoxicity. Part 1 (safety run-in) and Part 2: Dose: AUC5 Frequency: Day 1, Q3W Route: Intravenous Treatment Period: 4 cycles
Hospitalario Universitario A Coruña
A Coruña, La Coruña, Spain
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, Spain
RECRUITINGHospital General Universitario de Alicante
Alicante, Spain
RECRUITINGHospital Universitari Vall d' Hebron
Barcelona, Spain
RECRUITINGHospital Clínic De Barcelona
Barcelona, Spain
RECRUITINGHospital de la Santa Creu i Sant Pau
Barcelona, Spain
RECRUITINGHospital Parc Taulí
Barcelona, Spain
RECRUITINGHospital De Basurto
Bilbao, Spain
RECRUITINGICO Girona, Hospital Josep Trueta
Girona, Spain
RECRUITING...and 8 more locations
Part 2: Objective response per RECIST 1.1 based on investigator
Objective response is a confirmed complete response (CR) or partial response (PR), as determined by investigator per RECIST 1.1.
Time frame: From the date of the end of treatment until 12 months
Part 2: Duration of Response (DOR) per RECIST 1.1 based on investigator
DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause (whichever is earlier), for participants who demonstrate a confirmed CR or PR. Response will be determined by BICR per RECIST 1.1.
Time frame: From date of documentation of tumor response until date of first documented progression, assessed up to 12 months
Part 2:Overall Survival
OS is defined as the time from enrollment to the date of death from any cause.
Time frame: From the date of the end of treatment until 12 months
Part 2: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of treatment
Occurrence and severity of adverse events, with severity determined by NCI CTCAE v5.0
Time frame: From the subject's written consent to participate in the study through 90 days after the final administration of the drug