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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.


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Stage IV Melanoma

Thank you

Trial Information

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.


Inclusion Criteria:



- Patients may be entered in the study only if they meet all of the following criteria.

1. Male or female patients greater than or equal to 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. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

5. Life expectancy greater than or equal to 3 months;

6. At least 1 site of measurable disease by the Response Evaluation Criteria in
Solid Tumors version 1.1 (RECIST 1.1 version 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) greater than or equal to 1.5 x 109/L

- Platelet count greater than or equal to 100 x 109/L

- Hemoglobin greater than or equal to 9 g/dL

- Serum creatinine less than or equal to 1.5 X ULN and/or creatinine
clearance greater than or equal to 50 mL/min per the Cockcroft and Gault
formula

- Total serum bilirubin less than or equal to 1.5 X ULN

- Serum aspartate transaminase (AST/SGOT) or serum alanine transaminase
(ALT/SGPT) less than or equal to 2.5 X ULN, and less than or equal to 5 X
ULN if liver metastases are present

- PT/International normalized ratio (INR) less than or equal to 1.5 X ULN

- PTT less than or equal to 1.1 X ULN

8. 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;

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 less than 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 greater than or equal to 1 year;

11. Before study entry, written informed consent must be obtained from patient prior
to performing any study-related procedures.

Exclusion Criteria:

- Patients will not be entered in the study for any of the following reasons:

1. Known CNS lesions, except for asymptomatic, nonprogressive, 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 greater than or equal to 2.0 x 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;

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
greater than 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 greater than greater than or equal to 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 enrolment;

19. Patients with an allograft requiring immunosuppression;

20. Known positive human immunodeficiency virus (HIV), known surface antigen
positive for hepatitis B or hepatitis C positive;

21. History of hypersensitivity reactions to dacarbazine or its excipients;

22. Hypersensitivity to E7080 and/or E7080 chemical derivative; or

23. Have any other uncontrolled infection or medical condition which would interfere
with the conduct of the study.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety Parameter: Adverse Events

Outcome Description:

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.

Outcome Time Frame:

Until study termination; 3 years

Safety Issue:

Yes

Principal Investigator

Harish Dave, MD

Investigator Role:

Study Director

Investigator Affiliation:

Quintiles

Authority:

United States: Food and Drug Administration

Study ID:

E7080-702

NCT ID:

NCT01133977

Start Date:

March 2010

Completion Date:

August 2013

Related Keywords:

  • Stage IV Melanoma
  • Melanoma

Name

Location

New York Oncology HematologyAlbany, New York  12208
Texas Oncology, P.A. - DallasDallas, Texas  75246
Virgina Oncology AssociatesNorfolk, Virginia  
Meritus Center For Clinical ResearchHagerstown, Maryland  21740
Hematology and Oncology Associates of SC, LLC, Cancer Center of the CarolinasGreenville, South Carolina  29605