The primary objective will be to assess the safety and tolerability of this combination and to determine whether the MTD ofEMD 521873 is reached up to a dose of 0.45 mg/kg. Secondary objectives will be the evaluation of the PK, immunogenicity,…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the incidence of DLTs occurring during the first cycle
of administration of any dose of EMD 521873 following radiotherapy. This
endpoint will be used to determine the MTD of EMD 521873.
Secondary outcome
Additional safety variables (AEs, laboratory parameters, vital signs); serum
levels of anti-EMD 521873 antibodies to characterize the immunogenicity of EMD
521873; objective tumor response, change in circulating tumor cell numbers;
progression-free survival and overall survival; changes in leukocyte subsets
and molecular markers of immune activation
Background summary
Patients with stage IV NSCLC or stage IIIB NSCLC with malignant pleural
effusion have a dismal prognosis with a median overall survival time of
approximately 1 year after treatment with standard platinum-based first-line
chemotherapy with or without monoclonal antibodies. In the present trial,
active immunotherapy with EMD 521873 and radiation will be investigated as
maintenance therapy in subjects with SD or partial remission after first-line
chemotherapy. The combination of EMD 521873 with local tumor radiation is
expected to induce or enhance a cellular immune response against various tumor
antigens leading to control of tumor growth.
Study objective
The primary objective will be to assess the safety and tolerability of this
combination and to determine whether the MTD of
EMD 521873 is reached up to a dose of 0.45 mg/kg. Secondary objectives will be
the evaluation of the PK, immunogenicity, biological effects and antitumor
activity of EMD 521873 in this combination.
Study design
This open-label, dose-escalation trial consists of a 4 week screening phase, a
treatment phase, and a follow-up phase. After screening, eligible subjects will
receive local irradiation (5 x 4 Gy) given over 5 consecutive days, prior to
the first treatment cycle with EMD 521873. After a 2-day treatment-free
interval, intravenous infusions of EMD 521873 will be given on 3 consecutive
days in 3-week cycles until progression of disease (according to Investigator)
or unacceptable toxicity. Subjects will be hospitalized on days 1-4 of cycle 1.
Intervention
This is a trial with increasing doses of Selectikine in combination with
radiation. Groups of 3-6 patients (cohorts) will enter the study. The first
cohort will be treated at the dose level of 0.15 mg/kg and depending on the
tolerability of the drug additional cohorts of patients will be treated at
higher dose levels or , if the drug is not so well tolerated, at the same or
even lower dose levels.The highest dose level to be studied in this trial will
be 0.45 mg/kg. Before starting treatment of a new patient cohort at a higher
dose level, all data from the previous dose level will be evaluated by an
independent safety monitoring committee which includes the doctors involved in
the study, representatives from the sponsor and an independent physician.
Visits will take place on each day of radiation therapy (day -7 to day -3).
During treatment with EMD 521873 visits will take place on days 1-4, 8 and 15
of cycles 1 and 2; and on days 1-3 and 8 of all subsequent cycles.
Study burden and risks
The trial will be discontinued in the event of new findings that indicate a
relevant
increase in risk or deterioration in the risk-benefit relationship. The careful
selection of
trial sites with prior experience in managing patients with advanced NSCLC
treated with
radiation is expected to enhance both the safety and comfort of subjects in
this trial. In
addition, careful screening of subjects prior to enrolment is part of this
protocol to avoid
the inclusion of subjects who can be expected to be at increased risk for
developing severe
side effects after treatment with EMD 521873.
Frankfurter Str. 250
64293 Darmstadt
DE
Frankfurter Str. 250
64293 Darmstadt
DE
Listed location countries
Age
Inclusion criteria
• Male or female, aged >=18 years of age
• Signed written informed consent
• Effective contraception for male and female subjects of childbearing potential
• ECOG performance status 0 or 1
• Adequate hematological function defined by WBC >=3 x 109/L, neutrophils >=1.5 x 109/L, lymphocyte count >=0.5 x 109/L, platelet count >=100 x 109/L; hemoglobin >=9 g/L
• Estimated creatinine clearance >=50 mL/min according to the Cockcroft - Gault formula or 24-h urine sampling
• Adequate hepatic function defined by a total bilirubin level <=1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotrasferase (ALT) <=5 x ULN
Exclusion criteria
• Requirement for immunosuppressive treatment with the exception of inhalative corticosteroids or low-dose systemic corticosteroids (prednisone equivalent dose <=10 mg/day)
• Systemic autoimmune disease (e.g. lupus erythematodes, rheumatoid arthritis)
• Organ transplant recipients
• Active infections (including HIV, hepatitis B and C, tuberculosis)
• Known or clinically suspected brain metastases
• Active cardiovascular/cerebrovascular disease (e.g. symptomatic coronary vascular disease, congestive heart failure >= NYHA II, LVEF <50%, ventricular arrhythmia requiring medication, myocardial infarction or stroke) within previous 6 months
• Pericardial effusion
• Major impairment in pulmonary function: forced expiratory volume in 1 second (FEV1) <50% and diffusion capacity for carbon monoxide (DLCO) <50% of normal limit
• Any other significant disease that in the Investigator*s opinion would exclude the subject from the trial
• Known conditions associated with necroses of non-tumor bearing tissues (e.g. esophageal or gastroduodenal ulcers, ischemic bowel disease, chronic inflammations)
• Pregnancy or lactation
• Radiotherapy, chemotherapy, major surgery, biological therapy or any investigational drug within 30 days prior to the start of trial treatment
• Requirement for concurrent systemic anticancer treatment (chemotherapy, biological therapy)
• Pretreatment with anti-EGFR antibodies or tyrosine kinase inhibitors
• Participation in another interventional clinical trial within the past 30 days before start of trial treatment
• Known alcohol or drug abuse
• Any psychiatric condition that would prohibit the understanding or rendering of the informed consent
• Legal incapacity or limited legal capacity
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-007091-20-NL |
| CCMO | NL26310.031.08 |