Clinical trial NCT02054351: Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR)
Official title: A First-in-human Dose Escalation and Dose Finding Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: Advanced ovarian cancer
CLDN6 positive
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-02-04
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Advanced ovarian cancer is a high medical need indication. Cure is not available to these patients and treatment has palliative intent. A proportion of advanced stage ovarian cancer expresses substantial levels of Claudin 6 (CLDN6), a carcino-embryonic transmembrane protein, which is absent from normal adult human tissue. IMAB027 is a monoclonal antibody that binds to CLDN6. Preclinically IMAB027 was shown to inhibit tumor growth and to kill cancer cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This trial is a first-in-human dose escalation and dose finding Phase 1 trial of IMAB027 in patients with recurrent advanced ovarian cancer to assess the safety and tolerability, the pharmacokinetics, the antitumoral activity and the immunogenicity of IMAB027.


Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent
2. Female patients ≥18 years of age, no upper age limit
3. Histologically or cytologically confirmed CLDN6+ ovarian cancer of any histology type including primary peritoneal or fallopian tube tumors (histological documentation of the original primary tumor is required via a pathology report)
4. Performance status ECOG 0-2
5. Patients with measurable, non-measurable, or evaluable disease: Evaluable disease: defined as a confirmed CA-125 ≥2 x ULN, Measurable disease (RECIST 1.1): defined as at least one lesion that can be accurately measured in at least one dimension
6. Availability of a FFPE tumor tissue sample or tumor cell positive paracentesis fluid samples (abdominal or pleural cavity) for the assessment of CLDN6 positivity
7. Life expectancy of \>12 weeks
8. Adequate organ function defined as:

   Adequate hematologic function (ANC ≥1000/μl, platelets ≥100.000/μl, hemoglobin ≥9.0 g/dl (can be post transfusion)); Adequate renal function (serum creatinine ≤1.5 mg/dl \[114.5 μmol/l\] or creatinine clearance rate ≥30 ml/min); Adequate liver function (serum total bilirubin ≤2 x ULN, AST/ALT ≤3 x ULN)
9. Patients of child-bearing potential must have a negative β-HCG urine test within 72 hours before receiving treatment

Exclusion Criteria:

1. Patient is pregnant or breast-feeding
2. Prior allergic reaction or intolerance to a monoclonal antibody (humanized or chimeric)
3. Any prior anti-tumor therapy within 14 days prior to the start of IMAB027 treatment
4. Other concurrent anticancer therapies
5. HIV infection in medical history or active Hepatitis B or C infection requiring treatment
6. History of any one or more of the following cardiovascular conditions within the past 6 months: Myocardial infarction (T-Wave/Non-T-Wave), Unstable angina pectoris Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA), History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT). Patients with recent DVT who have been or are treated with therapeutic anti-coagulant agents (excluding warfarin) for at least 6 weeks are eligible
7. Other investigational agents or devices concurrently or within 14 days before start of IMAB027 treatment
8. Any hemoptysis or bleeding event that is clinically relevant within 2 weeks of first dose of study drug
9. Clinical symptoms of brain metastases or tumor-associated spinal cord compression
10. Need for continuous, systemic immunosuppressive therapy
11. Any other medical condition that would, in the opinion of the Investigator, limit the patient's ability to complete the study

Primary outcomes:
measure: Safety and tolerability
timeFrame: 24 month
Secondary outcomes:
measure: to assess pharmacokinetics
timeFrame: 24 month
measure: to assess antitumoral activity
timeFrame: up to 3 years
measure: to assess immunogenicity
timeFrame: 24 month
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UZ Brussels
city: Leuven
country: Belgium
facility: UZ Leuven
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Universitäts-Frauenklinik (UFK) Tübingen
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Frauenklinik
state: Baden-Württemberg
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Hämatologie-Onkologie
state: Sachsen
city: Kiel
country: Germany
facility: UKSH Kiel
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Senior Medical Director
role: STUDY_DIRECTOR
References: