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

Fallopian Tube Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01899599
• Other study ID #: GEXMab25201
• Secondary ID: 2013-000931-28
• Status: Completed
• Phase: Phase 2
• Start date: September 2013
• Est. completion date: July 28, 2017

Study information

• Verified date: October 2020
• Source: Glycotope GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: July 28, 2017
• Est. primary completion date: April 20, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Epithelial Cancer Recurrent
• Primary Peritoneal Cancer

Intervention

Drug:
• PankoMab-GEX
start dose 500mg at C0D1, maintenance dose 1700mg at CxD1, Number of Cycles: until progression or unacceptable toxicity develops.
• Placebo
start dose matching 500mg at C0D1, maintenance dose matching 1700mg at CxD1, Number of Cycles: until progression or unacceptable toxicity develops.

Locations

Country	Name	City	State
Germany	Investigator	Berlin
Germany	Investigator	Kiel
Germany	Investigator	Munich
Germany	Investigator	Munich
Germany	Investigator	Regensburg
Germany	Investigator	Stuttgart
Hungary	Investigator	Budapest
Hungary	Investigator	Debrecen
Hungary	Investigator	Szeged
Italy	Investigator	Meldola
Italy	Investigator	Milan
Italy	Investigator	Milan
Italy	Investigator	Rome
Poland	Investigator	Bydgoszcz
Poland	Investigator	Gdansk
Poland	Investigator	Lublin
Poland	Investigator	Olsztyn
Poland	Investigator	Poznan
Poland	Investigator	Rzeszow
Romania	Investigator	Brasov
Romania	Investigator	Bucharest
Romania	Investigator	Cluj-Napoca
Romania	Investigator	Cluj-Napoca
Romania	Investigator	Craiova
Romania	Investigator	Oradea
Romania	Investigator	Timisoara
Romania	Investigator	Timisoara
Russian Federation	Investigator	Kazan
Russian Federation	Investigator	Moscow
Russian Federation	Investigator	Moscow
Russian Federation	Investigator	Moscow
Russian Federation	Investigator	Oryol
Russian Federation	Investigator	Pyatigorsk
Russian Federation	Investigator	Rostov-on-Don
Russian Federation	Investigator	St Petersburg
Russian Federation	Investigator	St. Petersburg
Russian Federation	Investigator	St. Petersburg
Russian Federation	Investigator	Volgograd
Russian Federation	Investigator	Yaroslavl
Spain	Investigator	Barcelona
Spain	Investigator	Madrid
Spain	Investigator	Madrid
Spain	Investigator	Madrid
Spain	Investigator	Madrid
Spain	Investigator	Madrid
Spain	Investigator	Valencia
United Kingdom	Investigator	London
United Kingdom	Investigator	London
United Kingdom	Investigator	Northwood
United Kingdom	Investigator	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Glycotope GmbH

Countries where clinical trial is conducted

Germany,  Hungary,  Italy,  Poland,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	PFS will be determined by radiographic progression based on modified RECIST 1.1 or death of any cause.	from baseline till progression of disease or death
Secondary	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.	Safety will be determined on the occurrence of infusion-related reactions (IRR), treatment emergent adverse events (TEAE) and treatment emergent serious adverse events (TESAE).	from randomization until end of treatment
Secondary	Patient reported outcome	To evaluate the quality of life (QoL) and other health and health-economy related outcomes	from randomization until end of treatment