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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Treatment
Condition:	Ovarian Cancer
Interventions:	Biological: Abagovomab Biological: Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study population was recruited in 139 sites (Hospitals/University Clinics) distributed in Europe (Belgium, Czech Republic, France, Germany, Hungary, Italy, Poland and Spain) and US. Date of first patient randomised: 08 December 2006 Date of last patient randomised: 26 December 2008

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Study population was recruited in 139 sites (Hospitals/University Clinics) distributed in Europe (Belgium, Czech Republic, France, Germany, Hungary, Italy, Poland and Spain) and US.

Date of first patient randomised: 08 December 2006 Date of last patient randomised: 26 December 2008

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Abagovomab	2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Placebo	2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)

Participant Flow: Overall Study

	Abagovomab	Placebo
STARTED	593	295
TREATED	592	294
COMPLETED	545	272
NOT COMPLETED	48	23

Baseline Characteristics

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Reporting Groups

	Description
Abagovomab	2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Placebo	2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)

Baseline Measures

	Abagovomab	Placebo	Total
Number of Participants [units: participants]	593	295	888
Age [units: participants]
<=18 years	1	0	1
Between 18 and 65 years	447	227	674
>=65 years	145	68	213
Age [units: years] Mean ± Standard Deviation	56.4 ± 10.57	56.0 ± 10.47	56.3 ± 10.53
Gender, Customized [units: participants]
Female	593	295	888
Region of Enrollment [units: participants]
France	1	2	3
United States	91	47	138
Hungary	17	8	25
Czech Republic	54	28	82
Poland	53	25	78
Spain	55	48	103
Belgium	19	4	23
Germany	206	93	299
Italy	97	40	137
Histology of ovarian tumor [units: participants]
Serous/papillary	481	245	726
Endometrioid	38	21	59
Mucinous	6	3	9
Undifferentiated	14	7	21
Mixed tumor	18	7	25
Others	33	12	45
missing	3	0	3
Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ^[1] [units: participants]
0	460	240	700
1	131	55	186
2	2	0	2
Grade of histologic differentiation ^[2] [units: participants]
G1-G2	160	82	242
G3-G4	365	185	550
GX	12	4	16
not done	56	24	80
International Federation of Gynecology and Obstetrics (FIGO) stage ^[3] [units: participants]
III	513	252	765
IV	80	42	122
missing	0	1	1
Tumor size after debulking surgery [units: participants]
<= 1 cm	479	232	711
> 1 cm	114	63	177
Serum CA-125 after 3rd chemotherapy cycle [units: participants]
<= 35 U/ml	479	239	718
> 35 U/ml	114	55	169
missing	0	1	1

[1]	This scale and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The scale runs from the score 0 to 5, with 0 denoting the status "Fully active, able to carry on all pre-disease performance without restriction" and 5 the status "Dead".
[2]	Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type. GX Grade cannot be assessed (Undetermined grade) G1 Well-differentiated (Low grade) - best prognosis G2 Moderately differentiated (Intermediate grade) G3 Poorly differentiated (High grade) G4 Undifferentiated (High grade) - worst prognosis
[3]	International system of staging which identifies the spread of the ovarian cancer at the point of diagnosis [STAGE 1 - Tumour is confined to the ovary / ovaries; STAGE 2 – Tumour involves one or both ovaries and has extended into the pelvis; STAGE 3 – The tumour involves one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis and/or regional lymph node metastasis, includes liver capsule metastasis; STAGE: 4 – Distant metastasis beyond the peritoneal cavity, liver parenchymal metastasis.]

[1]

This scale and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The scale runs from the score 0 to 5, with 0 denoting the status "Fully active, able to carry on all pre-disease performance without restriction" and 5 the status "Dead".

[2]

Histologic grade, also called differentiation, refers to how much the tumor cells resemble normal cells of the same tissue type.

GX Grade cannot be assessed (Undetermined grade) G1 Well-differentiated (Low grade) - best prognosis G2 Moderately differentiated (Intermediate grade) G3 Poorly differentiated (High grade) G4 Undifferentiated (High grade) - worst prognosis

[3]

International system of staging which identifies the spread of the ovarian cancer at the point of diagnosis [STAGE 1 - Tumour is confined to the ovary / ovaries; STAGE 2 – Tumour involves one or both ovaries and has extended into the pelvis; STAGE 3 – The tumour involves one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis and/or regional lymph node metastasis, includes liver capsule metastasis; STAGE: 4 – Distant metastasis beyond the peritoneal cavity, liver parenchymal metastasis.]

Outcome Measures

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1. Primary:

Recurrence Free Survival Evaluated by Clinical Event Adjudication Committee (CEAC) [ Time Frame: Every 12 weeks up to recurrence or up to 3 months after last administered dose ]

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2. Secondary:

Overall Survival [ Time Frame: 2 years ]

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3. Secondary:

Safety [ Time Frame: 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 ]

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4. Secondary:

Time Course of Immunoresponse [ Time Frame: 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) ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The only disclosure restriction on the PI is that result communications shall be exchanged and discussed with the sponsor 60 days prior to submission for publication or presentation.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Clinical Research Director
Organization: Menarini Ricerche SpA
e-mail: abagovomab@menarini-ricerche.it

Publications:

Reinartz S, Kohler S, Schlebusch H, Krista K, Giffels P, Renke K, Huober J, Mobus 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.

Wagner U, Kohler S, Reinartz S, Giffels P, Huober J, Renke K, Schlebusch H, Biersack HJ, Mobus 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.

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):1568-1577.

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.

Responsible Party:	Menarini Group
ClinicalTrials.gov Identifier:	NCT00418574 History of Changes
Other Study ID Numbers:	ABA-01, AGO-OVAR 10, 2006-002801-30
Study First Received:	January 4, 2007
Results First Received:	July 1, 2011
Last Updated:	November 17, 2011
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board Germany: Paul-Ehrlich-Institut Germany: Ethics Commission Belgium: Directorate general for the protection of Public health: Medicines Belgium: Institutional Review Board Italy: Ethics Committee Czech Republic: State Institute for Drug Control Hungary: National Institute of Pharmacy Spain: Spanish Agency of Medicines Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products