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

This study has been completed.
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01133977
First received: May 21, 2010
Last updated: August 16, 2016
Last verified: August 2016

May 21, 2010
August 16, 2016
April 2010
June 2014   (final data collection date for primary outcome measure)
  • Dose Limiting Toxicity (DLT) of Lenvatinib Administered in Combination With Dacarbazine (for Phase 1b) [ Time Frame: From Day 1 through 21 days (one cycle) ] [ Designated as safety issue: Yes ]
    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.
  • 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 ] [ Designated as safety issue: Yes ]
    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.
  • Safety Parameter: Adverse Events [ Time Frame: Until study termination; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
  • Concomitant Meds [ Time Frame: Until study termination; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
  • Lab Tests [ Time Frame: Day 1 and every 28 of every cycle until study terminaton; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
  • ECGs [ Time Frame: Day 1 and 30 days after termination of therapy; 3 years ] [ Designated as safety issue: Yes ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
Complete list of historical versions of study NCT01133977 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: No ]
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.
  • Efficacy Parameter [ Time Frame: Time Frame: Progression-Free Survival (PFS) Until disease progression or death for 3 years ] [ Designated as safety issue: No ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
  • Efficacy Parameter [ Time Frame: Time Frame: Time to progression (TTP) Until disease progression or death for 3 years ] [ Designated as safety issue: No ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
  • Efficacy Parameter [ Time Frame: Time Frame: Overall survival (OS) Until death for 3 years ] [ Designated as safety issue: No ]
    Phase 1B: To determine the MTD of E7080 in combination with dacarbazine as determined by occurrence of dose-limiting toxicity at 3 ascending dose levels of E7080. Phase II: Safety and tolerability of E7080 at the MTD determined in Phase Ib in combination with dacarbazine as measured by rate of adverse events by body system and grade.
  • Efficacy Parameter [ Time Frame: Time Frame: Objective Response Rate (ORR) , Until termination of study drug or every 2 months up to 1 year during followup ] [ Designated as safety issue: No ]
    Objective Response Rate (ORR) , the number and percentage of patients with Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD)
  • 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 ] [ Designated as safety issue: No ]
    TTP, defined as the time from the date of randomization until the date of progressive disease.
  • Overall Survival (OS) (for Phase 2) [ Time Frame: From the date of randomization until death or up to approximately 2 years ] [ Designated as safety issue: No ]
    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.
  • 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 ] [ Designated as safety issue: No ]
    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.
Not Provided
 
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.

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.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Stage IV Melanoma
  • Drug: Lenvatinib
    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 Name: E7080
  • Drug: Lenvatinib
    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 Name: E7080
  • Drug: Dacarbazine
    Dacarbazine (1000 mg/m2) infusion over 60 minutes on Day 1 of each 21-day cycle.
    Other Name: Dacarbazine (DTIC)-Dome
  • Experimental: Lenvatinib + Dacarbazine (Phase 1b)
    Participants received 16 mg, 20 mg or 22 mg lenvatinib once daily in combination with dacarbazine
    Interventions:
    • Drug: Lenvatinib
    • Drug: Dacarbazine
  • 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
    Interventions:
    • Drug: Lenvatinib
    • Drug: Dacarbazine
  • Active Comparator: Dacarbazine (Phase 2)
    Participants received dacarbazine
    Intervention: Drug: Dacarbazine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
97
November 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients with histologically-confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer (AJCC)).
  2. No prior cytokine, chemotherapy, or targeted therapy for Stage IV melanoma.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  4. Life expectancy greater than or equal to 3 months.
  5. At least 1 site of measurable disease by RECIST 1.1.
  6. Adequate hematologic, renal, liver, and coagulation system function as defined by laboratory values performed within 21 days prior to initiation of dosing.
  7. 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:

  1. 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.
  2. Lactate dehydrogenase greater than or equal to 2.0 x upper limit of normal (ULN).
  3. 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.
  4. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures.
  5. Other active malignancy.
  6. History of or known carcinomatous meningitis.
  7. History of or known ocular melanoma.
  8. Are currently receiving any other treatment for the tumor (including palliative radiotherapy) aside from control of symptoms.
  9. 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.
  10. 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.
  11. 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.
  12. History of bleeding diathesis or coagulopathy.
  13. Current use of anti-coagulants such as Vitamin K antagonists, unfractionated heparin, or low molecular weight heparin.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Italy,   Spain,   United Kingdom
 
NCT01133977
E7080-702
No
Not Provided
Not Provided
Eisai Inc.
Eisai Inc.
Quintiles, Inc.
Study Director: Dave Harish Quintiles, Inc.
Eisai Inc.
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP