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

NCT01133977 | Completed Phase 1 Results

• 1 other identifier: E7080-702
• Study Type: interventional
• Target: 97
• Locations: 5 countries
• Sites: 27

Brief Summary

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.

Conditions

Stage IV Melanoma

Outcome Measures

Primary Outcomes (2)

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

  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.

  From Day 1 through 21 days (one cycle)

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

  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.

  From signing of informed consent up to 30 days after the last dose, up to approximately 2 years

Secondary Outcomes (1)

• Progression Free Survival (PFS) (for Phase 2)

  From the date of randomization until the date of disease progression or death (whichever was earlier) or up to approximately 2 years

Other Outcomes (3)

• Time to Progression (TTP) (for Phase 2)

  From the date of randomization until disease progression or death or up to approximately 2 years

• Overall Survival (OS) (for Phase 2)

  From the date of randomization until death or up to approximately 2 years

• Overall Response Rate (ORR) (for Phase 2)

  From the date of randomization until disease progression or death or up to approximately 2 years

Study Arms (3)

Lenvatinib + Dacarbazine (Phase 1b)

EXPERIMENTAL

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

Drug: Lenvatinib; Drug: Dacarbazine

Lenvatinib + Dacarbazine (Phase 2)

EXPERIMENTAL

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

Drug: Lenvatinib; Drug: Dacarbazine

Dacarbazine (Phase 2)

ACTIVE COMPARATOR

Participants received dacarbazine

Drug: Dacarbazine

Interventions

Lenvatinib DRUG

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

Also known as: E7080

Lenvatinib + Dacarbazine (Phase 1b)

Dacarbazine DRUG

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

Also known as: Dacarbazine (DTIC)-Dome

Dacarbazine (Phase 2); Lenvatinib + Dacarbazine (Phase 1b); Lenvatinib + Dacarbazine (Phase 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• Quintiles, Inc.: collaborator

Study Sites (27)

Unknown Facility

Hagerstown, Maryland, United States

Location

Unknown Facility

Albany, New York, United States

Location

Unknown Facility

Greenville, South Carolina, United States

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Unknown Facility

Dallas, Texas, United States

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Unknown Facility

Norfolk, Virginia, United States

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Unknown Facility

Berlin, 10249, Germany

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Berlin, 12351, Germany

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Berlin, 13585, Germany

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Heidelberg, 69120, Germany

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München, 81675, Germany

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Unknown Facility

Bari, 70126, Italy

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Unknown Facility

Milan, 20133, Italy

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Milian, 20141, Italy

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Unknown Facility

Napoli, 80131, Italy

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Unknown Facility

Siena, 53100, Italy

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Unknown Facility

Barcelona, Spain

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Unknown Facility

Madrid, 28033, Spain

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Unknown Facility

Madrid, 28034, Spain

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Unknown Facility

Madrid, 28050, Spain

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Unknown Facility

Valenica, 46014, Spain

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Unknown Facility

Dorset, United Kingdom

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Glasgow, United Kingdom

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Manchester, United Kingdom

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Unknown Facility

Metropolitan Borough of Wirral, United Kingdom

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Unknown Facility

Middlesex, United Kingdom

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Unknown Facility

Oxford, United Kingdom

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Unknown Facility

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Melanoma

Interventions

lenvatinib; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Dave Harish

  Quintiles, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: May 31, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2014
• Study Completion: November 1, 2014
• Last Updated: October 10, 2016
• Results First Posted: October 10, 2016

Record last verified: 2016-08

Locations

GB (7); DE (5); IT (5); US (5); ES (5)