Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Dacarbazine

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants received 16 mg, 20 mg or 22 mg lenvatinib once daily in combination with dacarbazine

Participants received lenvatinib per the maximum tolerated dose (MTD) as determined in the Phase Ib of the study in combination with dacarbazine

Lenvatinib tablets administered orally at doses of 16 mg, 20 mg, or 22 mg, once daily continuously over 3 weeks (21 days) during each 21-day cycle

Lenvatinib 20 mg (MTD/recommended Phase 2 dose as determined in Phase 1b of the study) administered once daily continuously over 3 weeks (21 days) during each 21-day cycle

Dacarbazine (1000 mg/m2) infusion over 60 minutes on Day 1 of each 21-day cycle.

Dave Harish

Primary:

* Phase Ib: To define the safety, tolerability and maximum tolerated dose (MTD) of lenvatinib administered in combination with dacarbazine.
* Phase II: To evaluate the safety and tolerability of lenvatinib administered in combination with dacarbazine, compared with dacarbazine alone.

Secondary:

-Phase II: To make a preliminary assessment of the efficacy of lenvatinib administered in combination with dacarbazine, compared with dacarbazine alone.

Safety was assessed by monitoring and recording all treatment emergent adverse events (AEs) and serious adverse events (SAEs); regular monitoring of clinical laboratory parameters; periodic measurement of vital signs and electrocardiograms (ECGs); dose limiting toxicities; performance of physical examinations; concomitant medications and procedures.

E7080 (Lenvatinib) in Combination With Dacarbazine Versus Dacarbazine Alone as First Line Therapy in Patients With Stage IV Melanoma

An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7080 (Lenvatinib) in Combination With Dacarbazine Versus Dacarbazine Alone as First Line Therapy in Patients With Stage IV Melanoma.

TTP, defined as the time from the date of randomization until the date of progressive disease.

OS, defined as the time from the date of randomization until the date of death. Few events of deaths (9 events in the Lenvatinib + Dacarbazine arm and 4 events in the Dacarbazine arm) were reported to calculate the median OS or to draw conclusions regarding the OS.

ORR, defined as percentage of participants with best confirmed response (complete response \[CR\] or partial response \[PR\]). A confirmatory scan was required after no less than 4 weeks and no later than 8 weeks, starting on the date that the response was first recorded.

DLTs were defined as clinically significant adverse events (AEs) occurring less than or equal to 21 days after commencing study treatment and considered by the Investigator to be possibly or probably related to study treatment.

Safety assessments consisted of monitoring and recording all AEs, including all Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0) grades, and SAEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. Details of AEs and SAEs are provided in the reported adverse event section.

PFS was defined as the time from the date of randomization of a participant until (1) the date of first documented progression of such participant's disease based on Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST v. 1.1) or (2) the date of such participant's death due to any cause. Progression was defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions, based on Investigator assessment according to RECIST 1.1. If missing assessments, imputed dates were used in the analysis.

Quintiles, Inc.

Eisai Inc.

Treatment emergent adverse events (TEAEs), defined as an AE that started/increased in severity on/after the first dose of study drug up to 30 days after final dose of study drug are reported.

Participants received 16 mg lenvatinib once daily continuously over 3 weeks (21 days) during each cycle in combination with dacarbazine (1000 mg/m2) on Day 1 of each 21-day cycle upto eight 21-day cycles (24 weeks) or more if participants experience clinical benefit

16 mg Lenvatinib + Dacarbazine (Phase 1b)

Participants received 20 mg lenvatinib once daily continuously over 3 weeks (21 days) during each cycle in combination with dacarbazine (1000 mg/m2) on Day 1 of each 21-day cycle upto eight 21-day cycles (24 weeks) or more if participants experience clinical benefit

20 mg Lenvatinib + Dacarbazine (Phase 1b)

Participants received 22 mg lenvatinib once daily continuously over 3 weeks (21 days) during each cycle in combination with dacarbazine (1000 mg/m2) on Day 1 of each 21-day cycle upto eight 21-day cycles (24 weeks) or more if participants experience clinical benefit

22 mg Lenvatinib + Dacarbazine (Phase 1b)

20 mg Lenvatinib + Dacarbazine (Phase 2)

Participants received dacarbazine (1000 mg/m2) on Day 1 of each 21-day cycle upto eight 21-day cycles (24 weeks) or more if participants experience clinical benefit

Dacarbazine (Phase 2)

Total

18 years and older

Age, Customized

Male

Female

Sex/Gender, Customized

A total of 40 participants were randomized in Dacarbazine (Phase 2) arm but only 39 participants received study drug and were included in the safety analysis set.

Eisai Medical Services

Participants with DLTs

Grade 3 hypertension

Grade 3 febrile neutropenia

Grade 3 thrombocytopenia

Participants received 16 mg lenvatinib once daily continuously over 3 weeks (21 days) during each cycle in combination with dacarbazine (1000 mg/m2) on Day 1 of each 21-day cycle upto eight 21-day cycles (24 weeks) or more if participants experience clinical benefit.

Safety Analysis Set: All participants enrolled in the Phase 1b portion of this study, except for those who (i) dropped out of the study prior to receiving any study drug, or (ii) were without any safety assessment following the first dose of study drug.

Dose Limiting Toxicity (DLT) of Lenvatinib Administered in Combination With Dacarbazine (for Phase 1b)

SAEs

Safety Analysis Set: All participants enrolled in the Phase 1b and Phase 2 portion of this study, except for those who (i) dropped out of the study prior to receiving any study drug, or (ii) were without any safety assessment following the first dose of study drug.

Number of Participants With Adverse Events/Serious Adverse Events (AEs/SAEs)

The current study was not powered or designed to determine superiority of the '20 mg Lenvatinib + Dacarbazine (Phase 2)' arm compared with 'Dacarbazine (Phase 2) ' arm.

All randomized participants who received at least one dose of study drug without major protocol eligibility violations were included in the Modified Intent-to-Treat (MITT) Analysis Set.

Spots Global Cancer Trial Database for E7080 (Lenvatinib) in Combination With Dacarbazine Versus Dacarbazine Alone as First Line Therapy in Patients With Stage IV Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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