Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00004094

Trial Description

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Title

An Open-label, Multi-center Dose Escalation Phase I Study to Investigate the Safety and Tolerability of a Continuous Infusion of the Bispecific T-cell Engager (BiTE) MT110 in Locally Advanced, Recurrent or Metastatic Solid Tumors Which Commonly Express EpCAM and Are Not Amenable to Curative Treatment

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Trial Acronym

MT110-101

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URL of the Trial

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Brief Summary in Lay Language

This phase I dose escalation study is intended to define the safety, tolerability and
maximal tolerable dose (MTD) of MT110 in patients with advanced solid tumors.

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Brief Summary in Scientific Language

MT110 is a bispecific (anti-EpCAM x anti-CD3) T-cell engager (BiTE) designed to link EpCAM
(epithelial cell adhesion molecule) expressing cells and T-cells resulting in T-cell
activation and a cytotoxic T-cell response against EpCAM+ cells. In vitro and ex-vivo data
indicate that EpCAM+ tumor cell lines are sensitive to MT110 mediated cytotoxicity.
Furthermore, data from in-vivo experiments with both MT110 and a mouse surrogate molecule
(muS110) have confirmed the activity of these molecules in inhibiting the formation of
metastases but also against established tumors. In vitro and ex-vivo data suggest that a
prolonged presence of the drug in target tissues may result in significant T-cell
recruitment, activation and expansion to/in target tissues, potentially resulting in
substantial anti-tumor activity in man.

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Organizational Data

  •   DRKS00004094
  •   2012/11/29
  •   2008/03/07
  •   no
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Secondary IDs

  •   2007-004437-42 
  •   NCT00635596  (ClinicalTrials.gov)
  •   MT110-101  (Micromet GmbH)
  •   EUDRACT No: 2007-004437-42 
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Health Condition or Problem studied

  •   Solid Tumors
  •   C00-C75 -  Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic and related tissue
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Interventions/Observational Groups

  •   Biological: MT110
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I
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Primary Outcome

- Overall frequency and intensity of adverse events (AEs) (clinical symptoms, laboratory abnormalities, serious adverse events [SAEs] and dose-limiting toxicities); time frame: one or more treatment cycles

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Secondary Outcome

- Pharmacokinetics of MT110; T-cell counts, kinetics, and activation status; Serum cytokine concentrations; Immunogenicity; Anti-tumor activity; Other progressive disease (PD) parameters; time frame: one or more treatment cycles

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2008/03/31
  •   70
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. Locally advanced, recurrent or metastatic solid tumors known to widely express EpCAM
and proven histology of the following entities:

- Adenocarcinoma of the lung

- Small cell lung cancer (SCLC)

- Gastric cancer or adenocarcinoma of gastro-esophageal junction

- Colorectal cancer (CRC)

- Hormone-refractory prostate cancer (HRPC)

- Breast cancer

- Ovarian cancer

Patients must not be amenable to curative therapy. Patients should have exhausted or
declined standard therapeutic options and previous therapies should have included at
least one course of chemotherapy.

2. Non-measurable disease or at least one measurable tumor lesion as per RECIST criteria

3. Age >/= 18 years

4. ECOG performance status </= 2

5. Life expectancy of at least 3 months

6. Must have recovered from the acute reversible effects of previous anti-cancer
chemotherapy, endocrine therapy, immunotherapy, radiotherapy or surgery.

- This generally means at least 4 weeks since major surgery, radical radiotherapy
or myelosuppressive chemotherapy (6 weeks for nitrosoureas or mitomycin C).

- At least 4-5 half-lives (t1/2) must have elapsed since treatment with an
investigational agent.

- At least 4 weeks since any hormonal therapy (except LHRH agonists for patients
with HRPC) prior to initiating MT110 treatment.

7. Ability to understand the patient information and informed consent form

8. Signed and dated written informed consent

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Exclusion Criteria

1. Evidence of central nervous system (CNS) metastases on baseline computer tomography
(CT) or magnetic resonance imaging (MRI) scan (mandatory for all patients), current
or past relevant history of other CNS pathology (except migraine, headache and minor
incidental findings in the MRI without any clinical manifestation within the last
five years). All minor incidental findings should be discussed with the Sponsor's
Medical Monitor).

2. Neutrophil count < 1,500/mm3 (= 1.5 x 10^9/l)

3. Platelet count < 100,000/mm3 (= 100 x 10^9/l)

4. White blood cells (WBC) < 3 x10^9/l

5. Hemoglobin < 9.0 g/dl

6. Abnormal renal or hepatic function as defined below:

- Alkaline phosphatase (AP)>/= 2.5 x upper limit of normal (ULN) and/or aspartate
aminotransferase (AST, SGOT), alanin aminotransferase (ALT, SGPT) >/= 2.0 x ULN
or AP, AST and/or ALT >/= 3 x ULN in case of liver metastases; γ-glutamyl
transpeptidase (GGT) >/= 5.0 x ULN

- Total bilirubin >/= 1.5 x ULN

- Creatinine clearance < 50 ml/min calculated by the Cockroft-Gault formula or
MDRD (modification of diet in renal disease)

- Lipase/amylase > 1.5 x ULN

- D-dimer >/= 10 x ULN

- Antithrombin activity < 70%

- International normalized ratio (INR) > ULN

- Partial thromboplastin time (PTT) > ULN

7. Oxygen (O2) saturation of < 92% (under room air condition)

8. Any concurrent anti-neoplastic therapy with the exception of radiotherapy for
palliation of symptoms after agreement by the Sponsor's Medical Monitor. No radiation
is allowed for defined measurable lesions according to RECIST. Patients with HRPC who
have received LHRH-agonist therapy for >1 month, should continue agonist therapy.

9. Any concurrent disease, medical or social condition that could affect compliance with
the protocol or interpretation of results as judged by the investigator. In
particular, patients with the following conditions are not allowed to enter the
study:

- Autoimmune and inflammatory diseases including vasculitis, rheumatoid arthritis,
systemic lupus erythematosus (SLE), multiple sclerosis and similar conditions

- Active infection or known bacteremia

- Known infection with human immunodeficiency virus (HIV) or chronic infection
with hepatitis B virus or hepatitis C virus

- Severe dyspnea or pulmonary dysfunction or need for continuous supportive oxygen
inhalation

- Insufficient cardiac function defined as NYHA (New York Heart Association) Grade
3 or 4

- History of acute or chronic pancreatitis

10. Chronic systemic corticosteroid therapy longer than 2 months or any other
immunosuppressive therapies or stem-cell transplantation.

11. Presence of human anti-murine antibodies (HAMA) or known hypersensitivity to
immunoglobulins or to other ingredients of the infusion solution.

12. Pregnant, nursing women or women of childbearing potential who are not willing to use
effective forms of contraception during participation in the study and at least three
months thereafter.

13. Male patients with partners of child-bearing potential who are not willing to use
effective contraception during the trial and for at least three months thereafter,
unless surgically sterile.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Amgen Research (Munich) GmbH
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    • Universitätsklinikum Hamburg-Eppendorf
    • Walter Fiedler, MD, Prof. 
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    • Universitätsklinikum Hamburg-Eppendorf
    • Walter Fiedler, MD, Prof. 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up complete
  •   2015/01/01
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   18
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.