Recurrent Epithelial Ovarian Carcinoma MedDRA version: 14.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PankoMab-GEX
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
Other descriptive name: PANKOMAB-GEX
Concentration unit: mg milligram(s)
Concentration type: range
Concent
Sponsors
Glycotope GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients over or equal to 18 years of age. 2. Histologically confirmed, TA-MUC1 positive, recurrent epithelial ovarian carcinoma. 3. Availability of tumor tissue samples (slices or block) for immune-histological confirmation of TA-MUC1 status (tissue samples may also be stored for other further specified biomarker assessments). 4. Patients should have received at least 2 lines but not more than 4 lines of chemotherapy prior to start of maintenance treatment. 5. Documented response to or stable disease following the most recent line of chemotherapy (any regimen and duration in accordance with local or international guidelines or within independent ethics committee [IEC] approved studies) and received last dose of said chemotherapy maximum 5 weeks prior to randomization (response to prior chemotherapy is defined as a partial/complete response according to radiological response criteria and/or a confirmed decline in tumor marker CA125 =50% from the pretreatment value for patients who have a pretreatment value =2 x the upper limit of normal [ULN]; stable disease is defined as stable disease according to radiological response criteria with a confirmed lack of increase in tumor marker CA125 from the pretreatment value for patients who have a pretreatment value =2 x ULN and no clinical progression). CA125 prior to randomization must be below ULN or CA125 levels must not increase >15% within a time frame >7 days if above ULN. 6. Treatment-free interval of maximum12 months immediately preceding the chemotherapy to which the patient has just responded. 7. Sensitive or resistant to the most recent platinum-based chemotherapy preceding the chemotherapy to which the patient has just responded (sensitive is thereby defined as a recurrence of disease >6 to =12 months after end of platinum-based chemotherapy and resistant is defined as a recurrence of disease =6 months after the end of platinum-based chemotherapy). 8. Eastern Cooperative Oncology Group (ECOG) performance status =1. 9. Recovered from all chemotherapy-related toxicities to grade 1 or grade 0 according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, with the exception of alopecia (any grade) and peripheral neuropathy (=grade 2). 10. Adequate bone marrow and hepatic function at Screening: - Hemoglobin over or equal to 9 g/dL - White blood cell count over or equal to 3.0 × 109/L - Absolute neutrophil count over or equal to 1.5 × 109/L - Platelet count over or equal to 100 × 109/L - Aspartate aminotransferase and alanine aminotransferase 1 year) must use highly effective contraceptives with a Pearl index 3 months. 13. Ability and willingness to give written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.
Exclusion criteria
Exclusion criteria: 1. Refractory to platinum-based chemotherapy (defined as remained progressive or became progressive under any previous platinum-based regimen). 2. Treatment-free interval of >12 months after the most recent antecedent platinum-based chemotherapy regimen. 3. Concomitant anti-tumor therapy or immunotherapy. 4. Treatment with monoclonal antibodies or investigational agents maximum 30 days before randomization (Note: prior anti-MUC1 therapy is not permitted at any time). 5. Limited field radiotherapy maximum 30 days before randomization (Note: extensive prior radiotherapy during or following the last line of chemotherapy is not permitted; radiotherapy prior to the last line of chemotherapy is permitted). 6. Prior allergic reaction to a monoclonal antibody, grade 3 infusion related reaction (IRR) or any grade 4 reaction to a monoclonal antibody. 7. Known sensitivity to any component of the test product. 8. Contraindication to the premedications used in this study (paracetamol/acetaminophen, H1 and/or H2 receptor antagonists, and steroids). 9. Clinical evidence of brain metastasis or leptomeningeal involvement. 10. Primary or secondary immune deficiency. 11. Clinically active infections >grade 2 using NCI CTCAE v4.0. 12. Active hepatitis B or C or infection with human immunodeficiency virus (HIV). 13. Myocardial infarction within 6 months prior to Screening. 14. Symptomatic congestive heart failure (New York Heart Association grade 3 or 4), unstable angina pectoris within 6 months prior to Screening, significant cardiac arrhythmia or history of stroke or transient ischemic attack within 1 year prior to Screening. 15. Prior or planned major surgery within 30 days prior to randomization and/or incomplete recovery from prior surgery. 16. Concomitant use of systemic steroids, except for inhaled, topical or nasal application within 30 days prior to randomization (Note: steroids used for premedication are permitted). 17. Active drug or alcohol abuse. 18. Any uncontrolled medical condition that may put the patient at high risk during treatment with an investigational drug, including unstable diabetes mellitus, vena cava syndrome, or chronic symptomatic respiratory disease. 19. Pregnancy or lactation. 20. Legal incompetence, limited legal competence, or detainment in an institution for official or legal reasons. 21. Receipt of any other investigational medicinal product within the last 30 days before randomization or any previous PankoMab-GEXTM administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary study objective is: To evaluate the efficacy of maintenance therapy with single-agent PankoMab-GEX™ compared to placebo as assessed by progression free survival (PFS) following chemotherapy in patients with recurrent epithelial ovarian carcinoma. ;Secondary Objective: The secondary study objectives are: - To evaluate the efficacy of PankoMab-GEX™ compared to placebo as assessed by patient survival and tumor response related criteria/parameters. - To evaluate the safety of maintenance therapy with single-agent PankoMab-GEX™ compared to placebo. - To evaluate the quality of life (QoL) and other health and health-economy related outcomes. - To evaluate potential efficacy and safety correlations of the tumor-specific epitope TA-MUC1 immuno-histochemical (IHC) score in the tumor tissue samples, soluble TA-MUC1 serum levels, serum pharmacokinetic (PK), pharmacodynamic (PD), genotyping regarding Fc? receptor status and potentially disease- or pathway-related parameters during maintenance therapy with single-agent PankoMab-GEX™ or placebo. ;Primary end point(s): Efficacy endpoints: The primary efficacy endpoint is PFS, as assessed by the site investigator and defined as the time interval from the date of randomization to the first date of documented disease progression using modified RECIST v1.1 (irRC) criteria or death due to any cause. ;Timepoint(s) of evaluation of this end point: Weeks 8, 14, 20, followed by 8-weekly exams for the first year and 12-weekly exams thereafter | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic endpoints: - PankoMab-GEXTM serum concentration before and after infusion in Cycles 0 to 6 for all patients treated with PankoMab-GEXTM. - PankoMab-GEXTM serum concentration at additional time points and pharmacokinetic (PK) profile for a subgroup of 20 patients treated with PankoMab-GEXTM. In addition, the relationship to response of PK parameters in the patients treated with PankoMab-GEX™ including detailed PK profiles in a subgroup of 20 patients will be evaluated as data permit. Safety endpoints: - Incidence of disease related symptoms. - Immunogenicity: incidence of anti-drug antibodies (ADAs). - Overall tolerability (standard safety assessments in terms of laboratory evaluations, vital signs, electrocardiogram [ECG], and physical examinations). - Incidence of adverse events (AEs) and IRRs. Secondary efficacy endpoints: - PFS, as assessed by independent central review. - Time to progression (TTP), according to modified RECIST v1.1 (irRC) or Gynecologic Cancer Intergroup (GCIG) criteria, whichever showed earlier progression, as assessed by independent central review. - The PFS rate at 6 months, as assessed on-site and by independent central review. - Objective response rate (ORR), as assessed on-site and by independent central review. - Clinical benefit rate (CBR), as assessed on-site and by independent central review. - Overall survival (OS). - QoL scores as assessed by European Oncology Research Trials Committee (EORTC) QoL questionnaires EORTC-QLQ-C30 and EORTC-QLQ-OV28 (according to availability of validated translations). - Utilization of disease-related resources such as concomitant medication, hospitalization (Medical Utilization). - Relationship of TA-MUC1-IHC score in the tumor tissue samples, soluble TA-MUC1 serum levels and FC? receptor status to activity parameters. - Relationship of stratification factors to activity parameters. Pharmacokinetic endpoints: - PankoMab-GEXTM serum concentration before and aft | — |
Countries
Germany, Hungary, Italy, Poland, Romania, Russian Federation, Spain, United Kingdom
Contacts
Public ContactDr. Zimmermann - Clinical Trial Mng
Glycotope GmbH
Outcome results
None listed