An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7080 in Combination with Dacarbazine versus Dacarbazine Alone as First Line Therapy in Patients with Stage IV Melanoma.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-016049-24-GB
• Date of registration: 17/03/2010
• Prospective Registration: Yes
• Primary sponsor: Eisai Inc.
• Public title: An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7080 in Combination with Dacarbazine versus Dacarbazine Alone as First Line Therapy in Patients with Stage IV Melanoma.
• Scientific title: An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7080 in Combination with Dacarbazine versus Dacarbazine Alone as First Line Therapy in Patients with Stage IV Melanoma.
• Date of first enrolment: 02/07/2010
• Target sample size: 185
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016049-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Germany, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients may be entered in the study only if they meet all of the following criteria:
1. Male or female patients =18 years of age;
2. Patients with histologically-confirmed metastatic melanoma (stage IV, AJCC);
3. No prior cytokine, chemotherapy, or targeted therapy for Stage IV melanoma.
• Patients who received adjuvant therapy must be at least 30 days from the last dose. Patients who received adjuvant vaccine therapy must be at least 6 months from the last dose.
• Isolated limb perfusion therapy is not allowed. Prior resection for Stage III or Stage IV disease is allowed as long as the patient has unresectable lesions at the time of randomization.
4. ECOG performance status of 0 or 1;
5. Life expectancy =3 months;
6. Measurable disease (by RECIST 1.1 criteria);
7. Adequate hematologic, renal, liver, and coagulation system function as defined by laboratory values performed within 21 days prior to initiation of dosing.
• Absolute neutrophil count (ANC) =1.5 x 109/L
• Platelet count =100 x 109/L
• Hemoglobin =9 g/dL
• Serum creatinine =1.5 X ULN and/or creatinine clearance = 50 mL/min per the Cockcroft and Gault formula
• Total serum bilirubin =1.5 X ULN
• Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase (ALT/SGPT) =2.5 X ULN, and =5 X ULN if liver metastases are present
• PT/International normalized ratio (INR) =1.5 X ULN
• PTT =1.1 X ULN
8. Blood pressure must be well-controlled (=140/90 mmHg at screening) with or without antihypertensive medication. Patients must have no history of hypertensive crisis or hypertensive encephalopathy;
9. Fertile men should use an effective method of contraception during treatment and for at least 3 months after completion of treatment as directed by their physician;
10. Pre-menopausal women and women <2 years after the onset of menopause should have a negative pregnancy test at screening. Pre-menopausal women must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of study drug. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for =1 year;
11. Before study entry, written informed consent must be obtained from patient prior to performing any study-related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will not be entered in the study for any of the following reasons:
1. Known CNS lesions, except for asymptomatic non-progressing, treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. 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, 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 = 2.0 x ULN;
3. Subjects with proteinuria >1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with 24-hour urine protein =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 =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 =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 =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;
14. Refractory nausea and vomiting, malabsorption, significant bowel resection, or any other medical condition that would preclude adequate absorption or result in the inability to take oral medication;
15. Significant cardiovascular impairment (history of congestive heart failure > New York Heart Association (NYHA) Grade II (See Appendix 5), unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
16. Any history of cerebral vascular accident (CVA), transient ischemic attack (TIA), or = Grade 2 peripheral vascular disease unless they have had no evidence of active disease for at least 6 months prior to randomization
17. Active hemoptysis (defined as bright red blood of ½ teaspoon or more) within the 30 days prior to study entry;
18. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the 6 months prior to enrollment;
19. Patients with an allograft requiring immunosuppression;
20. Known positive human immunodeficiency virus (HIV), known surface antigen positive for hepatitis B or C;
21. History of hypersensitivity reactions to dacarbazine or its excipients;
22. Hypersensitivity

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stage IV Melanoma
MedDRA version: 13.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: E7080
Product Code: E7080
Pharmaceutical Form: Tablet
Other descriptive name: E7080
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Product Name: E7080
Product Code: E7080
Pharmaceutical Form: Tablet
Other descriptive name: E7080
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Product Name: E7080
Product Code: E7080
Pharmaceutical Form: Tablet
Other descriptive name: E7080
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Dacarbazine
Product Name: Dacarbazine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DACARBAZINE
CAS Number: 4342034
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 1000-

Primary Outcome(s)

Main Objective: • Phase Ib: to define the safety, tolerability and maximum tolerated dose (MTD) of E7080 administered in combination with dacarbazine in patients with Stage IV melanoma.
• Phase II: to evaluate the safety and tolerability of E7080 administered in combination with dacarbazine, compared with dacarbazine alone, in patients with Stage IV melanoma.

Primary end point(s): The primary exploratory efficacy endpoint will be the median progression-free survival (PFS) defined as the time from the date of randomization of a patient until the sooner of (1) the date of first documented progression of such patient’s disease based on investigator assessments according to RECIST criteria, or (2) the date of such patient’s death due to any cause.

Secondary Objective: The secondary objective of the Phase II portion of the study is to make a preliminary assessment of the efficacy of E7080 administered in combination with dacarbazine, compared with dacarbazine alone, in patients with Stage IV melanoma.

Secondary ID(s)

E7080-702