Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR)

Ovarian Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054351
• Other study ID #: GM-IMAB-002-01
• Secondary ID: 2013-002755-1516
• Status: Completed
• Phase: Phase 1
• Start date: February 6, 2014
• Est. completion date: October 28, 2015

Study information

• Verified date: November 2021
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: October 28, 2015
• Est. primary completion date: October 28, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• IMAB027
Stage 1 (Intrapatient dose escalation): The starting dose is set to 1 mg/m2, followed by 10 mg/m2, 30 mg/m2 and 100 mg/m2 Stage 2 (Interpatient dose escalation): 4 dose level 100 mg/m2, 300 mg/m2, 600 mg/m2, 1000 mg/m2 Extension period: 4 dose level 100 mg/m2, 300 mg/m2, 600 mg/m2, 1000 mg/m2

Locations

Country	Name	City	State
Belgium	UZ Brussels	Brussels
Belgium	UZ Leuven	Leuven
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Gemeinschaftspraxis Hämatologie-Onkologie	Dresden	Sachsen
Germany	Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	UKSH Kiel	Kiel	Schleswig-Holstein
Germany	Universitätsmedizin Mainz	Mainz	Rheinland-Pfalz
Germany	Universitäts-Frauenklinik (UFK) Tübingen	Tübingen	Baden-Württemberg
Germany	Universitätsklinikum Ulm, Frauenklinik	Ulm	Baden-Württemberg

Sponsors (1)

Lead Sponsor	Collaborator
Ganymed Pharmaceuticals GmbH

Countries where clinical trial is conducted

Belgium,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	Safety profile including type, frequency, severity, relationship of adverse events to investigational medicinal product, dose limiting toxicities, maximum tolerated dose	24 month
Secondary	to assess pharmacokinetics	Cmax, AUC, terminal half-life and related pharmacokinetic parameters of IMAB027	24 month
Secondary	to assess antitumoral activity	Disease control rates (CR, PR, SD), ratio previous/current remission time intervals and overall survival	up to 3 years
Secondary	to assess immunogenicity	Frequency of anti-IMAB027 antibodies	24 month

External Links

•   Link to plain language summary of the study on the Trial Results Summaries website
•   Link to results and other applicable study documents on the Astellas Clinical Trials website