PankoMab-GEX™ Versus Placebo as Maintenance Therapy in Advanced Ovarian Cancer

Brief Title

PankoMab-GEX™ Versus Placebo as Maintenance Therapy in Advanced Ovarian Cancer

Official Title

A Double-blind, Placebo-controlled, Randomized, Phase 2 Study to Evaluate the Efficacy and Safety of Maintenance Therapy With PankoMab-GEX™ After Chemotherapy in Patients With Recurrent Epithelial Ovarian Carcinoma

Brief Summary

      Efficacy of PankoMab-GEX vs Placebo in maintaining a response to chemotherapy in advanced
      ovarian, fallopian tube or primary peritoneal cancer.
    

Detailed Description

      The study is to evaluate the efficacy of PankoMab-GEX vs Placebo in maintaining response
      after 2nd to 5th line of chemotherapy in patients with epithelial ovarian or fallopian tube
      or primary peritoneal cancer. Patients must have responded to platinum based chemotherapy in
      a previous line, while the response to the most recent Pt-based chemotherapy must not have
      lasted more than 12 months. In addition the response between most recent 2 lines of
      chemotherapy prior start of study medication must not have lasted more than 12 months.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression free survival

Secondary Outcome

 To assess the safety and tolerability of maintenance therapy with single-agent PankoMab-GEX™ compared to placebo in patients with metastatic or recurrent ovarian or fallopian tube carcinoma or primary peritoneal carcinoma.

Condition

Ovarian Epithelial Cancer Recurrent

Intervention

PankoMab-GEX

Study Arms / Comparison Groups

 PankoMab-GEX

Description:  1700mg, i.v., q3w

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

216

Start Date

September 2013

Completion Date

July 28, 2017

Primary Completion Date

April 20, 2017

Eligibility Criteria

        Inclusion Criteria:

          1. Female patients ≥18 years of age

          2. Histologically-confirmed, TA-MUC1-positive, recurrent epithelial ovarian, or
             fallopian-tube cancer or primary peritoneal cancer with high-grade (Grade 2 or 3)
             serous features or a serous component

          3. Availability of tumor tissue samples (slices or block) for immune-histological
             confirmation of TA-MUC1 status (tissue samples could also be stored for other further
             specified biomarker assessments)

          4. Patients were to have received at least 2 lines but not more than 5 lines of
             chemotherapy prior to start of maintenance treatment; neo-adjuvant lines did not count
             as previous lines of treatment

          5. Patients had to have a documented response to or SD following the most recent line of
             chemotherapy (any regimen and duration in accordance with local or international
             guidelines or within IEC-approved studies) and received the last dose of said
             chemotherapy ≤6 weeks prior to randomization (response to prior chemotherapy was
             defined as a PR/CR according to radiological response criteria and/or a confirmed
             decline in tumor marker CA125 ≥50% from the pre-treatment value for patients who had a
             pre-treatment value ≥2 x the upper limit of normal [ULN]; SD was defined as stable
             disease according to radiological response criteria with a confirmed lack of increase
             in tumor marker CA125 from the pre-treatment value for patients who had a
             pre-treatment value ≥2 × ULN and no clinical progression). Prior to randomization,
             CA125 had to be below the ULN, or CA125 levels were not to increase >15% within a time
             frame >7 days if above the ULN

          6. Progression-free interval of ≤12 months immediately preceding the chemotherapy to
             which the patient had just responded

          7. Sensitive or resistant to the most recent platinum-based chemotherapy preceding the
             chemotherapy to which the patient had just responded (sensitivity was thereby defined
             as a recurrence of disease >6 to ≤12 months after the end of platinum-based
             chemotherapy, and resistantance was defined as a recurrence of disease ≤6 months after
             the end of the 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 NCI-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 ≥9 g/dL

               -  White blood cell count ≥3.0 × 109/L

               -  Absolute neutrophil count ≥1.5 × 109/L- Platelet count ≥100 × 109/L

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × ULN (<5
                  × ULN in case of liver metastases)

               -  Bilirubin <1.5 × ULN (<3 × ULN in case of liver metastases)

               -  Creatinine <1.5 × ULN

         11. Any patient with childbearing potential (i.e. not surgically sterile or
             post-menopausal for >1 year) had to use highly effective contraceptives with a Pearl
             index <1% according to the "Note for guidance on non-clinical safety studies for the
             conduct of human clinical trials and marketing authorization for pharmaceuticals"
             (CPMP/ICH/286/95) of the European Medicines Agency (EMA). (Although pregnancy was
             unlikely to occur in this patient population, any patient with childbearing potential
             had to be withdrawn from the study in the event of pregnancy)

         12. Life expectancy >3 months

         13. Ability and willingness to give written informed consent

        Exclusion criteria:

          1. Refractory to platinum-based chemotherapy (defined as remained progressive or became
             progressive under any previous platinum-based regimen)

          2. Progression-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 ≤30 days before
             randomization (prior anti-MUC1 therapy was not permitted at any time)

          5. Limited-field radiotherapy ≤30 days before randomization (extensive prior radiotherapy
             during or following the last line of chemotherapy was not permitted; radiotherapy
             prior to the last line of chemotherapy was permitted)

          6. Prior allergic reaction to a monoclonal antibody, Grade 3 IRR or any Grade 4 reaction
             to a monoclonal antibody

          7. Known sensitivity to any component of the test product

          8. Contraindication to the pre-medication used in this study (paracetamol/acetaminophen,
             H1 and/or H2 receptor antagonists, or steroids)

          9. Clinical evidence of brain metastasis or leptomeningeal involvement

         10. Patients with second primary cancer, except adequately treated non-melanoma skin
             cancer, curatively treated in-situ cancer of the cervix, ductal carcinoma in situ,
             Stage 1 Grade 1 endometrial carcinoma, or other solid tumors including lymphomas
             (without bone marrow involvement) curatively treated with no evidence of disease for
             ≥5 years

         11. Primary or secondary immune deficiency

         12. Clinically active infections >Grade 2 using NCI-CTCAE version 4.0

         13. Active hepatitis B or C or infection with human immunodeficiency virus (HIV)

         14. Myocardial infarction within 6 months prior to Screening

         15. 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

         16. Prior or planned major surgery within 30 days prior to randomization and/or incomplete
             recovery from prior surgery

         17. Concomitant use of systemic steroids, except for inhaled, topical or nasal application
             within 30 days prior to randomization (steroids used for pre-medication were
             permitted)

         18. Active drug or alcohol abuse

         19. Any uncontrolled medical condition that could have put the patient at high risk during
             treatment with an investigational drug, including unstable diabetes mellitus, vena
             cava syndrome, or chronic symptomatic respiratory disease

         20. Pregnancy or lactation

         21. Legal incompetence, limited legal competence, or detainment in an institution for
             official or legal reasons

         22. Receipt of any other investigational medicinal product within the last 30 days before
             randomization or any previous PankoMab-GEX™ administration
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jonathan Ledermann, MD, , 

Location Countries

Germany

Location Countries

Germany

NCT ID

NCT01899599

Organization ID

GEXMab25201

Secondary IDs

2013-000931-28

Responsible Party

Sponsor

Study Sponsor

Glycotope GmbH

Study Sponsor

Jonathan Ledermann, MD, Principal Investigator, UCL Cancer Institute, 90 Tottenham Court Road, London W1T 4TJ, UK

Verification Date

October 2020