Efficacy Multicentre Trial of ImmunoTherapy Vaccination With Abagovomab to Treat Ovarian Cancer Patients

Ovarian Cancer Clinical Trial

— MIMOSA  

Official title:

A Randomised,Double Blind, Placebo Controlled, Multicentre Trial of Abagovomab Maintenance Therapy in Patients With Epithelial Ovarian Cancer After Complete Response to First Line Chemotherapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00418574
• Other study ID #: ABA-01
• Secondary ID: AGO-OVAR 102006-
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: January 4, 2007
• Last updated: November 17, 2011
• Start date: December 2006
• Est. completion date: June 2011

Study information

• Verified date: November 2011
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardGermany: Paul-Ehrlich-InstitutGermany: Ethics CommissionBelgium: Federal Agency for Medicines and Health Products, FAMHPBelgium: Institutional Review BoardItaly: Ethics CommitteeCzech Republic: State Institute for Drug ControlHungary: National Institute of PharmacySpain: Spanish Agency of MedicinesPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the benefit of vaccination with Abagovomab, an experimental immunotherapy in ovarian cancer patients. The benefit will be evaluated in terms of time the remission status is kept as well as prolongation of life expectancy.

Description:

Standard initial treatment of ovarian cancer patients includes both surgery and chemotherapy which in the vast majority of cases achieves the disappearance of ovarian cancer lesions. This status, called "clinical remission" which means having no evidence of cancer on CT scan or physical examination needs to be carefully follow up in order to confirm the maintenance of the remission status or to early detect if the cancer grows again and then start a new chemotherapy. At present, no approved therapies exist for the maintenance treatment of patients who achieved the clinical remission.

This trial aims to evaluate if the repeated vaccination with Abagovomab creates an immunoresponse which is able to fight the cancer cells thus keeping the remission status as long as possible and help patients live disease-free and longer.

Patients who achieve the remission status after chemotherapy will be screened for study participation and if they meet the criteria for inclusion they will start to receive a single subcutaneous injection every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase). The duration of treatment is up to approximately 4 years or it will be stopped in case relapse occurs.

In order to evaluate the real benefit of vaccination, the experimental treatment includes Abagovomab (the active drug) or placebo (the vehicle only, without drug), with a double chance to receive Abagovomab. Assignment of Abagovomab or placebo will be done by a computerised system and nobody in the study will know which treatment has been allocated until study end.

Patients will be visited every 4 weeks and will undergo CT scan of pelvis and abdomen every 12 weeks in order to confirm the remission status or to early detect if relapse eventually occurs. This will be done in blind condition (i.e. without being aware which treatment the patient is going to receive) for the first part of the study which is expected to last four years. After then the overall status of patient will continue to be monitored by phone contact for additional five years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 888
• Est. completion date: June 2011
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

At a maximum of 12 weeks after the last cycle of first line standard platinum/taxane intravenous (IV) or intraperitoneal (IP) chemotherapy, patients must fulfill all the following inclusion criteria:

• Age >/= 18 years;

• Properly executed written informed consent;

• History of histological and CA125 (> 35 U/ml) confirmed diagnosis of stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer;

• History of debulking surgery and 6-8 cycles of standard platinum/taxane based non-investigational IV-IP chemotherapy;

• Complete clinical response defined as:

• Normal physical examination;

• No symptoms suggestive of persistent cancer;

• No definite evidence of disease by computed tomography (CT) of the abdomen and pelvis within the previous 4 weeks;

• Negative chest x-ray (or chest CT scan) within the previous 4 weeks;

• Serum CA125 within the normal laboratory range.

• Adequate hematologic, renal and hepatic function:

• Absolute Neutrophil Count (ANC) >/=1.5 * 109/l;

• Platelets >/= 75 * 109/l;

• Haemoglobin >/= 6.2 mmol/l (>9.9 g/dl);

• Serum creatinine </= 1.5 * ULN (Upper Limit of Normal);

• Bilirubin </= 1.5 * ULN; AST, ALT, AP </= 2.5 * ULN.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) </= 2.

Exclusion Criteria:

Patients are ineligible to participate in the study, if any of the following criteria are present:

• any other invasive malignancies, with the exception of non-melanoma skin cancer or cervical carcinoma in situ, within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy;

• known active autoimmune disease requiring chronic treatment with immunosuppressive agents (e.g., rheumatoid arthritis, ulcerative colitis, etc.);

• known immune deficiency (e.g. HIV, hypogammaglobulinemia, etc.);

• known infection with hepatitis B, or hepatitis C;

• history of recent myocardial infarction (</= 6 months) or decompensated heart failure (New York Heart Association - NYHA class >/= III);

• previous or concomitant use of any anti-cancer therapy other than the platinum-taxane based 1st line chemotherapy for ovarian cancer; any maintenance or consolidation therapy is not permitted after completion of standard front line chemotherapy.

• concomitant use of any other investigational agent;

• any prior investigational anti-cancer vaccine or monoclonal antibody;

• known allergy to murine proteins;

• any significant medical or psychiatric condition, drug or alcohol abuse that might prevent the patient from complying with all study procedures;

• clinically significant active infection;

• concomitant use of any immunosuppressive agent (e.g., steroids, cyclosporin, etc.);

• major surgery within the previous 2 weeks;

• radiotherapy within the previous 4 weeks;

• any significant toxicity from prior chemotherapy;

• unreliability or inability to follow protocol requirements;

• potentially childbearing and not willing to use adequate contraceptive methods throughout the entire study period;

• pregnancy.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Biological:
• Abagovomab
2 mg/ml SC (subcutaneously)
• Placebo
2 mg/ml SC (subcutaneously)

Locations

Country	Name	City	State
Belgium	Algemeen Stedelijk Ziekenhuis Aalst	Aalst
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Universitair Ziekenhuis Gent Medische Oncologie 4B-Z	Gent
Belgium	CHU de Liége (Sart Tilman)	Liège
Belgium	Clinique Sainte Elizabeth	Namur
Belgium	AZ Sint Augustinus, Oncologisch Centrum GVA	Wilrijk
Czech Republic	Fakultni nemocnice Brno	Brno
Czech Republic	MOU Zluty Kopec	Brno
Czech Republic	Nemocnice Ceske Budejovice, a.s.	Ceske Budejovice
Czech Republic	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czech Republic	Krajska nemocnice Liberec, oddeleni gynekologicko porodnicke	Liberec
Czech Republic	Fakultni nemocnice Olomouc	Olomouc
Czech Republic	Fakultni Nemocnice Ostrava	Ostrava
Czech Republic	Krajska nemocnice	Pardubice
Czech Republic	Gynekologicko-porodnicka klinika FN Plzen	Plzen
Czech Republic	Fakultni nemocnice Královské Vinohrady	Praha
Czech Republic	Vseobecna Fakultni Nemocnice	Praha 2
Czech Republic	Fakultni nemocnice Bulovka	Praha 8
Czech Republic	Krajska nemocnice T. Bati	Zlin
France	Institut Bergonié	Bordeaux Cedex
France	Centre Jean Bernard	Le Mans Cedex
France	Centre Catherine de Sienne	Nantes Cedex
France	Hôpital Hotel Dieu	Paris
Germany	Charité - Campus Virchow Klinikum	Berlin
Germany	Helios Kliniken GmbH, Klinikum Buch	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Klinikum Bremen-Mitte gGmbH	Bremen
Germany	Klinikum Chemnitz GmbH	Chemnitz
Germany	St.-Josefs-Hospital Cloppenburg	Cloppenburg
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Evangelisches Krankenhaus	Düsseldorf
Germany	Kreisklinik Ebersberg gGmbH	Ebersberg
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum	Essen
Germany	Klinikum der JWG Universität Frankfurt	Frankfurt
Germany	Universitätsklinikum	Freiburg
Germany	Universitätsklinikum	Göttingen
Germany	Klinikum der Ernst-Moritz-Universität	Greifswald
Germany	Martin-Luther-Universität Halle-Wittenberg, Klinikum der Medizinischen Fakultät	Halle/Saale
Germany	Universitätskrankenhaus Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Jena	Jena
Germany	St. Vincentius Kliniken AG	Karlsruhe
Germany	Klinikum Kassel	Kassel
Germany	Universitätsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Klinikum der Universität zu Köln	Köln
Germany	Kreiskrankenhaus Leonberg	Leonberg
Germany	Asklepios Klinik Lich	Lich
Germany	Vincenz-Krankenhaus	Limburg
Germany	Klinik St. Marienstift	Magdeburg
Germany	Otto-von-Guericke-Universität	Magdeburg
Germany	Städtisches Klinikum Magdeburg	Magdeburg
Germany	Johannes-Gutenberg-Universität	Mainz
Germany	Universitätsklinikum Gießen u. Marburg	Marburg
Germany	Klinikum der Universität München-Innenstadt	München
Germany	Klinikum Großhadern	München
Germany	Klinikum rechts der Isar	München
Germany	Klinikum Offenbach GmbH	Offenbach
Germany	St. Vincenz-Krankenhaus Paderborn	Paderborn
Germany	Elblandkliniken Meißen-Radebeul GmbH	Radebeul
Germany	Krankenhaus St. Josef	Regensburg
Germany	Klinikum Südstadt der Hansestadt Rostock	Rostock
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum	Ulm
Germany	Klinikum der Stadt Villingen-Schwenningen GmbH	Villingen-Schwenningen
Germany	r. Horst Schmidt Kliniken GmbH	Wiesbaden
Germany	St. Josefs-Hospital	Wiesbaden
Germany	Klinikum der Stadt Wolfsburg-FrauenklinikWolfsburg	Wolfsburg
Hungary	Fovárosi Önkormányzat Szent Margit Kórháza, Onkológia	Budapest
Hungary	Semmelweis Egyetem II. sz. Szülészeti és Nogyógyászati Klinika	Budapest
Hungary	Semmelweis Egyetem, I sz. Szülészeti és Nogyógyászati Klinika	Budapest
Hungary	Debreceni Egyetem Orvos és Egészségtudományi Centrum, Szülészetl es Nogyógyászatl Klinika	Debrecen
Hungary	Petz Aladar Megyei Oktató Kórház, Onkoradiológia	Gyor
Hungary	Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Kórháza, Szülészet-Nogyógyászati Osztály	Nyíregyháza
Hungary	Pécsi Tudományegyetem, ÁOK Szülészeti és Nogyógyászati Klinika	Pécs
Hungary	Komárom-Esztergom Megyei Onkormanyzat Szent Borbála Kórház, Szülészet-Nogyógyászati Osztály	Tatabanya
Italy	Unità Operativa Ginecologia e Ostetricia 2^, Università degli studi di Bari, Policlinico	Bari
Italy	Ospedale S. Orsola Malpighi, Oncologia Medica	Bologna
Italy	Universtita' Cattolica del Sacro Cuore Dipartimento di Oncologia	Campobasso
Italy	DH Oncologico U.O. Medicina Oncologica Ospedale Ramazzini	Carpi (MO)
Italy	Oncologia Medica Ospedale di Faenza - AUSL di Ravenna	Faenza
Italy	Azienda Ospedaliera - Universitaria Careggi	Firenze
Italy	Azienda Ospedaliera San Martino - Padiglione Malattie Complesse, Dipartimento di Oncologia Medica	Genova
Italy	Istituto Europeo di Oncologia - Divisione di Ginecologia	Milano
Italy	Istituto Nazionale dei Tumori di Milano	Milano
Italy	Policlinico di Modena, Dipartimento di Oncologia ed Ematologia	Modena
Italy	Istituto Nazionale per lo studio e la cura dei tumori "Fondazione Pascale" Oncologia Medica	Napoli
Italy	Azienda Ospedaliera San Carlo - Oncologia Medica	Potenza
Italy	Ospedali Riuniti Bianchi-Melacrino-Morelli - Oncologia Medica	Reggio di Calabria
Italy	Arcispedale Santa Maria Nuova, Oncologia Medica	Reggio Emilia
Italy	Dipartimento di Ginecologia ed Ostetricia Policlinico Universitario Gemelli	Roma
Italy	Policlinico Umberto I D.H. Oncologico Oncologia Medica	Roma
Italy	Ospedale Casa Sollievo della Sofferenza - Unita' Operativa di Ostetricia e Ginecologia	San Giovanni Rotondo (FG)
Italy	Dipartimento di Discipline Ginecologiche e Ostetriche - Universita degli Studi di Torino - Azienda ospedaliera O.I.R.M.-S'Anna	Torino
Poland	Wojewódzki Szpital Specjalistyczny Nr 4	Bytom
Poland	Oddzial Onkologii Wojewódzki Szpital Specjalistyczny	Czestochowa
Poland	Wojewodzkie Centrum Onkologii, Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Gdansk
Poland	"Centrum Onkologii, Instytut im. M. Sklodowskiej-Curie, Oddzial w Krakowie,	Krakow
Poland	Vesalius Kraków	Krakow
Poland	Klinika Chemioterapii Nowotworów Akademii Medycznej w Lodzi, Regionalny Osrodek Onkologiczny	Lodz
Poland	Oddzial Chemioterapii ZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Klinika Onkologii, Oddzial Chemioterapii Akademii Medycznej w Poznaniu	Poznan
Poland	SPZOZ Wojewodzki Szpital Specjalistyczny Nr 3, Oddzial Onkologii	Rybnik
Poland	Wojewodzki Szpital Zespolony, Oddzial Onkologii Klinicznej	Torun
Poland	Centralny Szpital Kliniczny MSWiA, Klinika Onkologii, Hematologii i Chorob Wewnetrznych	Warszawa
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie, Klinika Nowotworów Narzadów Plciowych Kobiecych	Warszawa
Poland	Wojskowy Instytut Medyczny; Klinika Onkologii Centralnego Szpitala Klinicznego MON	Warszawa
Spain	Hospital Germans Trias y Pujol	Badalona
Spain	Hospital Clinic i Provincial de Barcelona, Servicio de Oncologia	Barcelona
Spain	Hospital Vall d'Hebrón, Servicio de Oncologia	Barcelona
Spain	Hospital Reina Sofia	Córdoba
Spain	Hospital de Elche, Servico de Oncologia	Elche
Spain	Instituto Catalán de Oncología - Hospital Universitari de Girona "Dr. Josep Trueta". Oncologia Medica	Girona
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital Juan Ramón Jiménez de Huelva	Huelva
Spain	Complejo Hospitalario de Jaén	Jaen
Spain	Centro Oncológico Regional de Galicia, Servicio de Oncologia Medica	La Coruna
Spain	Hospital Universitario Arnau de Vilanova, Servicio de Oncologia	Lerida
Spain	Hospital Clinico San Carlos, Servicio de Oncología Medica	Madrid
Spain	MD Anderson Internacional Espana	Madrid
Spain	Hospital Clinico de Malaga. Servicio de Oncologia	Málaga
Spain	Hospital de Mataró	Mataró
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Son Dureta, Servicio de Oncología	Palma de Mallorca
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Hospital Clínico Universitario de Santiago de Compostela	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
United States	Harry and Jeanette Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Colorado	Denver	Colorado
United States	Wayne State University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Hackensack University Medical Center, Obstetrics and Gynecology Oncology	Hackensack	New Jersey
United States	Indiana University Cancer Pavilion	Indianapolis	Indiana
United States	Women's Cancer Center	Las Vegas	Nevada
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	The West Clinic	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	Memorial Sloan-Kettering Cancer Centre	New York	New York
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Women and Infants Hospital of Rhode Island	Providence	Rhode Island
United States	The Cancer Care Center	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	Curtis and Elizabeth Anderson Cancer Institute	Savannah	Georgia
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

United States,  Belgium,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Poland,  Spain, 

References & Publications (4)

Pfisterer J, du Bois A, Sehouli J, Loibl S, Reinartz S, Reuss A, Canzler U, Belau A, Jackisch C, Kimmig R, Wollschlaeger K, Heilmann V, Hilpert F. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol. 2006 Oct;17(10):1568-77. — View Citation

Reinartz S, Köhler S, Schlebusch H, Krista K, Giffels P, Renke K, Huober J, Möbus V, Kreienberg R, DuBois A, Sabbatini P, Wagner U. Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). Clin Cancer Res. 2004 Mar 1;10(5):1580-7. — View Citation

Sabbatini P, Dupont J, Aghajanian C, Derosa F, Poynor E, Anderson S, Hensley M, Livingston P, Iasonos A, Spriggs D, McGuire W, Reinartz S, Schneider S, Grande C, Lele S, Rodabaugh K, Kepner J, Ferrone S, Odunsi K. Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin Cancer Res. 2006 Sep 15;12(18):5503-10. — View Citation

Wagner U, Köhler S, Reinartz S, Giffels P, Huober J, Renke K, Schlebusch H, Biersack HJ, Möbus V, Kreienberg R, Bauknecht T, Krebs D, Wallwiener D. Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001. Clin Cancer Res. 2001 May;7(5):1154-62. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence Free Survival Evaluated by Clinical Event Adjudication Committee (CEAC)	The Recurrence free survival correspond to the time from date of randomization to documented disease recurrence or death. Disease recurrence is defined as the appearance of any lesion or development of tumor-related symptoms evaluated by medical examination and must be confirmed by a documented CT scan.	Every 12 weeks up to recurrence or up to 3 months after last administered dose	No
Secondary	Overall Survival	2 years survival rate	2 years	No
Secondary	Safety	Safety was analyzed in all patients who received at least 1 dose administration.; Adverse event (AE) are defined as events which started on or after the first dose of study medication and on or before the date of the final study visit, or within 12 weeks of the last dose if the final study visit was not performed.	Along treatment administration and up to double blind observation period. i.e. for each patient after the first dose administration till the f inal study visit, or within 12 weeks of the last dose	Yes
Secondary	Time Course of Immunoresponse	Time course of immunologic parameters (anti-anti-idiotypic antibody - Ab3) will be assessed in all patients, by comparing levels at baseline (week 0), at week 10 after first dose administration and at end of treatment (at week 4 or week 12 after the last administered dose, as appropriate).	at baseline, at week 10 after first dose administration and at final study visit (at week 4 or week 12 after the last administered dose, as appropriate)	No