Phase I study of monoclonal antibody ch14.18/CHO continuous infusion in patients with neuroblastoma

JRCT ID: jRCT2091220181

Registered date:25/06/2014

Basic Information

• Recruitment status: COMPLETED
• Health condition(s) or Problem(s) studied: neuroblastoma
• Date of first enrollment: 26/09/2014
• Target sample size: 9
• Countries of recruitment: Japan
• Study type: Interventional

Intervention(s)

Intervention type:DRUG
Name of intervention:APN311
Dose form / Japanese Medical Device Nomenclature:INJECTION
Route of administration / Site of application:INTRAVENOUS DRIP
Dose per administration:10
mg/m2
Dosing frequency / Frequency of use:OTHER, SPECIFY
10 consecutive days in 35-day cycle
Planned duration of intervention:up to 5 cycles
Intended dose regimen:Ch14.18/CHO is administered as continuous infusion over 10 consecutive days every 5 weeks.
detailes of teratment arms:
Comparative intervention name:
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Outcome(s)

Primary Outcome

-Adverse events, vital signs (blood pressure, pulse rate, temperature) and changes in clinical laboratory assessments
-Assessment of pain intensity

Secondary Outcome

-Pharmacokinetic parameters
-Pharmacodynamic parameters
-Immunogenicity (HACA)
-Anti-tumor activity in patients with evaluable/measureable disease

Key inclusion & exclusion criteria

• Age minimum: >= 12month old
• Age maximum: <= 29age old
• Gender: Both

Include criteria

Male and female patients will be considered eligible to enter the study if they satisfy all of the following inclusion criteria:
a)>= 12 months and =< 29 years of age at the time of study entry
b)Diagnosis of neuroblastoma according to the INSS criteria
c)Having received at least one previous high dose treatment followed by stem cell rescue after conventional therapy to reduce tumor burden fulfilling one of the following criteria:
-refractory disease with residual tumor
-relapse after previous treatment
d)Life expectancy of at least 12 weeks.
e)Performance status greater or equal 70% (Lansky Score or Karnofsky)
f)Consent to the placement of a central venous line, if one has not already been placed
g)Off any standard or experimental treatments for at least two weeks prior to study entry and be fully recovered from the short-term major toxic effects
h)No immediate requirements for palliative chemotherapy, radiotherapy or surgery
i)At least 4 weeks after major surgery (e.g. laparotomy or thoracotomy) and fully recovered from any post-surgical complications
j)Negative test for HIV, Hepatitis B, and Hepatitis C
k)Females of childbearing potential must have a negative pregnancy test. Both male and female patients of childbearing potential must agree to use an effective birth control method from signing a consent form until 3 months after the end of treatment. Female patients who are lactating must agree to stop breast-feeding from the start of study treatment until 1 month after the end of treatment.
l)Patient may have had prior CNS metastasis provided the following criteria are all met:
-The patient's CNS disease has been previously treated,
-The patient's CNS disease has been clinically stable for four weeks prior to starting this study (assessment must be made clinically and by CT or MRI),
-The patient is off steroids for CNS disease for four weeks prior to starting on study and during the course of the study
m)Patients with seizure disorders may be enrolled if on anticonvulsants and are well controlled and if no seizures occurred within the last 6 weeks prior to starting trial treatment
n)All patients and/or their parents or legal guardians must sign a written informed consent
o)Laboratory testing
-Shortening fraction of >= 30 % by Echocardiogram
-no dyspnea at rest and a pulse oximetry > 94% on room air
-Adequate bone marrow function as defined by ANC > 1,000/mcL, platelets >= 50,000/mcL and hemoglobin > 9.0 g/dL
-Adequate liver function, as defined by an ALT or AST < 5 x normal and a total bilirubin < 1.0 mg/dL
-Adequate renal function, as defined by a serum creatinine <1.5 mg/dL or a creatinine clearance > 60 mL/minute/1.73 m2

Exclude criteria

Patients are NOT eligible for this study if they meet any of the following exclusion criteria:
a)Patients with hypersensitivity against one component of the investigational product or against mouse proteins
b)Progressive disease with a rising tumor marker value or an increasing tumor size evaluated by MIBG scan/CT/MRI
c)Previous treatment with an anti-GD2 antibody (e.g. ch14.18/SP2/0, ch14.18/CHO)
d)Platelet transfusion dependency
e)Significant intercurrent illnesses and/or any of the following:
-Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance
-Patients with significant psychiatric disabilities or uncontrolled seizure disorders
-Patients with active infections or active peptic ulcer, unless these conditions are corrected or controlled
-Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade >2)
-Patients with clinically significant, symptomatic pleural effusions
f)Requirement, or likely requirement, for corticosteroid or other immunosuppressive drugs
g)Concurrent treatment with any non-trial anticancer therapies

Related Information

Primary Sponsor

Yoshiyuki Takahashi, MD, PhD
Department of Developmental Pediatrics
Nagoya University Graduate School of Medicine
65 Tsurumai-cho, Showa-ku, Nagoya
466-8550, Japan

• Source(s) of Monetary Support: Japan Medical Association
• Secondary ID(s): JMA-IIA00181