- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01133977
E7080 (Lenvatinib) in Combination With Dacarbazine Versus Dacarbazine Alone as First Line Therapy in Patients With Stage IV Melanoma
August 16, 2016 updated by: Eisai Inc.
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.
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
97
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Berlin, Germany, 10249
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Berlin, Germany, 12351
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Berlin, Germany, 13585
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Heidelberg, Germany, 69120
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Muenchen, Germany, 81675
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Bari, Italy, 70126
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Milan, Italy, 20133
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Milian, Italy, 20141
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Napoli, Italy, 80131
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Siena, Italy, 53100
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Barcelona, Spain
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Madrid, Spain, 28034
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Madrid, Spain, 28033
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Madrid, Spain, 28050
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Valenica, Spain, 46014
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Dorset, United Kingdom
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Glasgow, United Kingdom
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Manchester, United Kingdom
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Middlesex, United Kingdom
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Oxford, United Kingdom
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Southampton, United Kingdom
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Wirral, United Kingdom
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Maryland
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Hagerstown, Maryland, United States
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New York
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Albany, New York, United States
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South Carolina
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Greenville, South Carolina, United States
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Texas
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Dallas, Texas, United States
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Virginia
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Norfolk, Virginia, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients with histologically-confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer (AJCC)).
- No prior cytokine, chemotherapy, or targeted therapy for Stage IV melanoma.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Life expectancy greater than or equal to 3 months.
- At least 1 site of measurable disease by RECIST 1.1.
- Adequate hematologic, renal, liver, and coagulation system function as defined by laboratory values performed within 21 days prior to initiation of dosing.
- Blood pressure must be well-controlled (less than or equal to 140/90 mmHg at screening) with or without antihypertensive medication. Patients must have no history of hypertensive crisis or hypertensive encephalopathy.
Exclusion Criteria:
- Known central nervous system (CNS) lesions, except for asymptomatic, nonprogressive, treated brain metastases. Treatment for brain metastases must have been completed at least 4 weeks prior to Day 1 and may include whole brain radiotherapy (WBRT), radiosurgery [RS; Gamma Knife, linear accelerator (LINAC), or equivalent] or a combination as deemed appropriate by the treating physician. Dexamethasone must be discontinued at least 3 weeks prior to Day 1. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
- Lactate dehydrogenase greater than or equal to 2.0 x upper limit of normal (ULN).
- Subjects with proteinuria greater than 1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with 24-hour urine protein greater than or equal to 1 g/24 hours will be ineligible.
- Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures.
- Other active malignancy.
- History of or known carcinomatous meningitis.
- History of or known ocular melanoma.
- Are currently receiving any other treatment for the tumor (including palliative radiotherapy) aside from control of symptoms.
- Received treatment in another clinical study within the 30 days prior to commencing study treatment or patients who have not recovered from side effects of an investigational drug to grade less than or equal to 1, except for alopecia.
- Received radiotherapy within the 30 days prior to commencing study treatment or have not recovered from side effects of all radiation-related toxicities to grade less than or equal to 1, except for alopecia.
- Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury within the 28 days prior to commencing study treatment. Minor surgery such as Portacath placement or skin biopsy is permitted if greater than or equal to 7 days have passed.
- History of bleeding diathesis or coagulopathy.
- Current use of anti-coagulants such as Vitamin K antagonists, unfractionated heparin, or low molecular weight heparin.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Lenvatinib + Dacarbazine (Phase 1b)
Participants received 16 mg, 20 mg or 22 mg lenvatinib once daily in combination with dacarbazine
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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
Other Names:
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
Other Names:
Dacarbazine (1000 mg/m2) infusion over 60 minutes on Day 1 of each 21-day cycle.
Other Names:
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Experimental: Lenvatinib + Dacarbazine (Phase 2)
Participants received lenvatinib per the maximum tolerated dose (MTD) as determined in the Phase Ib of the study in combination with dacarbazine
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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
Other Names:
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
Other Names:
Dacarbazine (1000 mg/m2) infusion over 60 minutes on Day 1 of each 21-day cycle.
Other Names:
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Active Comparator: Dacarbazine (Phase 2)
Participants received dacarbazine
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Dacarbazine (1000 mg/m2) infusion over 60 minutes on Day 1 of each 21-day cycle.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Dose Limiting Toxicity (DLT) of Lenvatinib Administered in Combination With Dacarbazine (for Phase 1b)
Time Frame: From Day 1 through 21 days (one cycle)
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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.
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From Day 1 through 21 days (one cycle)
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Number of Participants With Adverse Events/Serious Adverse Events (AEs/SAEs)
Time Frame: From signing of informed consent up to 30 days after the last dose, up to approximately 2 years
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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.
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From signing of informed consent up to 30 days after the last dose, up to approximately 2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression Free Survival (PFS) (for Phase 2)
Time Frame: From the date of randomization until the date of disease progression or death (whichever was earlier) or up to approximately 2 years
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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.
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From the date of randomization until the date of disease progression or death (whichever was earlier) or up to approximately 2 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Progression (TTP) (for Phase 2)
Time Frame: From the date of randomization until disease progression or death or up to approximately 2 years
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TTP, defined as the time from the date of randomization until the date of progressive disease.
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From the date of randomization until disease progression or death or up to approximately 2 years
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Overall Survival (OS) (for Phase 2)
Time Frame: From the date of randomization until death or up to approximately 2 years
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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.
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From the date of randomization until death or up to approximately 2 years
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Overall Response Rate (ORR) (for Phase 2)
Time Frame: From the date of randomization until disease progression or death or up to approximately 2 years
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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.
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From the date of randomization until disease progression or death or up to approximately 2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Dave Harish, Quintiles, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2010
Primary Completion (Actual)
June 1, 2014
Study Completion (Actual)
November 1, 2014
Study Registration Dates
First Submitted
May 21, 2010
First Submitted That Met QC Criteria
May 27, 2010
First Posted (Estimate)
May 31, 2010
Study Record Updates
Last Update Posted (Estimate)
October 10, 2016
Last Update Submitted That Met QC Criteria
August 16, 2016
Last Verified
August 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Protein Kinase Inhibitors
- Lenvatinib
- Dacarbazine
Other Study ID Numbers
- E7080-702
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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