Clinical trial NCT00459823: A Dose Escalation Study of E7107 Administered IV (Bolus) on Days 1, 8, and 15 Every 28 Days to Patients With Solid Tumours
Official title: A Phase I Open-Label, Single-Arm, Dose Escalation Study of E7107 Administered IV (Bolus) on Days 1, 8, and 15 Every 28 Days to Patients With Solid Tumours
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Cancer
Keywords: Cancer
solid tumors
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2007-04-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Two-centre, open-label, non-randomized, dose-finding phase I study to determine the MTD of E7107 administered by intravenous infusion (as a 2-5 minutes bolus) on days 1, 8 and 15 every 28 days in patients with solid tumors, for whom therapy of proven efficacy does not exist or is not longer effective.


Eligibility criteria: INCLUSION CRITERIA:

Patients must meet all of the inclusion criteria outlined below in order to be eligible to participate in the study.

1. Patients with histologically and/or cytologically confirmed solid tumours who have progressed after receiving approved therapies for their disease and for whom no curative therapies are available.
2. Surgery and radiotherapy must have been completed at least four weeks prior to study entry, and prior chemotherapy and other anti-cancer therapy, excluding bisphosphonates at a steady dose level, must have been discontinued for at least two weeks previously. All acute toxicities related to these treatments must have resolved.
3. Aged \>= 18 years.
4. ECOG performance status score of 0 or 1.
5. Written informed consent prior to any study specific screening procedures, which will include voluntary additional consent to provide specimens specifically for pharmacogenomic analysis, with the understanding that the patient may withdraw consent at any time without prejudice.
6. Willing and able to comply with the protocol for the duration of the study.
7. Anticipated life expectancy \> three months.
8. After MTD has been reached: patients must have measurable disease according to RECIST criteria.

EXCLUSION CRITERIA:

Patients with the following characteristics will not be eligible for the study:

1. Symptomatic or progressive brain tumours or brain or leptomeningeal (CNS) metastases requiring clinical intervention, except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least two weeks before starting treatment with E7107.
2. Any of the following laboratory parameters:

   1. haemoglobin \< 9 g/dL (5.6 mM)
   2. neutrophils \<1.5 x 10\^9/L
   3. platelets \<100 x 10\^9/L
   4. serum bilirubin \>25 ìM (1.5 mg/dL)
   5. liver function tests (defined as AST and ALT) with values \>3 x ULN (5 x ULN if liver metastases are present)
   6. serum creatinine \> 105µM (or \>1.5 mg/L) or creatinine clearance \< 40 mL/min
3. Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection.
4. Clinically significant cardiac impairment or unstable ischemic heart disease (greater than Class III according to NYHA classification) including a myocardial infarction within six months of study start.
5. Bleeding or thrombotic disorders, or using therapeutic dosages of anticoagulants.
6. History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance.
7. Pregnancy or lactation (all women of childbearing potential must have a negative pregnancy test before inclusion in the study; peri-menopausal women must have been amenorrheic for at least 12 months, otherwise pregnancy test is required).
8. Fertile persons who are not willing to use adequate contraception (defined as two forms of contraception including a barrier method).
9. Patients with a marked screening or baseline prolongation of QT/QTc interval (i.e., repeated demonstration of a QTc interval \> 450 msec); a history of additional factors of TdP (i.e., heart failure, hypokalaemia, family history of Long QT Syndrome).
10. Legal incapacity.
11. After MTD has been reached: Second malignancy within the past 5 years, except for carcinoma in situ of the cervix, basal cell carcinoma of the skin.

Primary outcomes:
measure: To determine MTD of E7107. Safety and tolerability.
timeFrame: Every six weeks.
Secondary outcomes:
measure: Pharmacokinetics of E7107. Evaluation of anti-tumor activity. To investigate potential biomarkers of pharmacodynamic effect.
timeFrame: Every 21 days.
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Department of Medical Oncology, Erasmus University Medical Centre
city: Barcelona
country: Spain
facility: Medical Oncology Service. Vall d'Hebron University Hospital
Study officials:
affiliation: Eisai Limited
name: Jantien Wanders, M.D.
role: STUDY_DIRECTOR
References: