Clinical trial NCT01684878: Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)
Official title: A Two-Part, Randomized Phase III, Double-Blind, Multicenter Trial Assessing The Efficacy And Safety of Pertuzumab In Combination With Standard Chemotherapy Vs. Placebo Plus Standard Chemotherapy In Women With Recurrent Platinum-Resistant Epithelial Ovarian Cancer And Low HER3 mRNA Expression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-09-13
Enrollment: 208
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This two-part, multicenter study will evaluate the safety, tolerability and efficacy of pertuzumab in combination with standard chemotherapy in women with recurrent platinum-resistant epithelial ovarian cancer. In the non-randomized Part 1 safety run-in, participants will receive pertuzumab plus either topotecan or paclitaxel. In the randomized, double-blind Part 2 of the study, participants will receive either pertuzumab or placebo in combination with chemotherapy (topotecan, paclitaxel, or gemcitabine).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, and/or fallopian tube cancer that is platinum-resistant or refractory
* Low Human epidermal growth factor receptor (HER) 3 messenger ribonucleic acid (mRNA) expression
* At least one measurable and/or non-measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
* Left ventricular ejection fraction (LVEF) greater than or equal to (\>/=) 50 percent (%)
* Negative serum pregnancy test in women of childbearing potential
* Women of childbearing potential must agree to use effective contraception as defined by protocol during and for at least 6 months post study treatment

Exclusion Criteria:

* Non-epithelial tumors
* Ovarian tumors with low malignant potential (borderline tumors)
* History of other malignancy of prognostic relevance within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma, or tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the breast
* Previous treatment with more than 2 chemotherapy regimens
* Any prior radiotherapy to the pelvis or abdomen
* History or evidence on physical/neurological examination of central nervous system disease unrelated to cancer (uncontrolled seizures), unless adequately treated with standard medical therapy
* Pre-existing peripheral neuropathy \>/= common toxicity criteria (CTC) grade 2 (applicable for paclitaxel cohort only)
* Inadequate organ function
* Uncontrolled hypertension or clinically significant cardiovascular disease
* Current known infection with human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV), or hepatitis C virus (HCV)
* Current chronic daily treatment with corticosteroids (\>/= 10 mg per day of methylprednisolone or equivalent), excluding inhaled steroids
* History of receiving any investigational treatment within 28 days prior to first study drug administration
* For Part 2 of the trial: prior enrollment into Part 1 of the trial
* Concurrent participation in any therapeutic clinical trial

Primary outcomes:
measure: Part 1: Percentage of Participants With Adverse Events (AEs)
timeFrame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
measure: Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)
timeFrame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Secondary outcomes:
measure: Part 1- Objective Response Rate (ORR)
timeFrame: Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)
measure: Part 2- Objective Response Rate (ORR)
timeFrame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
measure: Part 1: PFS Assessed by the Investigator
timeFrame: Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)
measure: Part 2: Progression-free Survival (PFS) Assessed by the Investigator
timeFrame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
measure: Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score
timeFrame: Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)
measure: Part 2: Percentage of Participants With Adverse Events (AEs)
timeFrame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)
measure: Part 2: Overall Survival
timeFrame: Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie
city: Wien
country: Austria
facility: Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Herlev
country: Denmark
facility: Herlev Hospital; Onkologisk afdeling
city: København Ø
country: Denmark
facility: Rigshospitalet, Onkologisk Klinik
city: Bordeaux
country: France
facility: Institut Bergonie; Oncologie
city: Caen
country: France
facility: Centre Francois Baclesse; Oncologie
city: Dijon
country: France
facility: Centre Georges Francois Leclerc; Oncologie 3
city: Montpellier cedex 5
country: France
facility: CRLCC Val dAurelle Paul Lam
city: Paris
country: France
facility: Hopital Tenon; Oncologie Radiotherapie
city: Pierre Benite
country: France
facility: Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont
city: Plerin
country: France
facility: Clinique Armoricaine Radiologie; Hopital de Jour
city: Saint Herblain
country: France
facility: Ico Rene Gauducheau; Oncologie
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin; Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy; Oncologie Medicale
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe
city: Düsseldorf
country: Germany
facility: Evangelischen Krankenhauses Düsseldorf; Frauenklinik
city: Essen
country: Germany
facility: Universitätsklinikum Essen; Zentrum Für Frauenheilkunde
city: Essen
country: Germany
facility: Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gynäkologische Onkologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg; Frauenklinik
city: Greifswald
country: Germany
facility: Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie
city: Hannover
country: Germany
facility: Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
city: Kiel
country: Germany
facility: UNI-Klinikum Campus Kiel Klinik f.Gynäkologie u.Geburtshilfe
city: Koeln
country: Germany
facility: St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe
city: Konstanz
country: Germany
facility: Klinikum Konstanz, Frauenklinik
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München; Frauenklinik & Poliklinik
city: Offenbach
country: Germany
facility: Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe
city: Ravensburg
country: Germany
facility: Hämatologisch/Onkologische Praxis Dr. Herbrick - Zipp/Prof. Dr. Decker, Studienzentrum
city: Rostock
country: Germany
facility: Universitätsfrauen- und Poliklinik am Klinikum Suedstadt
city: Tübingen
country: Germany
facility: Universitätsklinik Tübingen; Frauenklinik
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm Am Michelsberg; Frauenklinik
city: Wiesbaden
country: Germany
facility: HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie
city: Napoli
country: Italy
facility: Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica
state: Campania
city: Roma
country: Italy
facility: Istituto Regina Elena; Oncologia Medica A
state: Lazio
city: Genova
country: Italy
facility: Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica
state: Liguria
city: Brescia
country: Italy
facility: A.O.Spedali Civili; Ostetricia e Ginecologia
state: Lombardia
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Pisa
country: Italy
facility: A.O.U Pisana; Dipartimento di Ginecologia Oncologica
state: Toscana
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Groningen
country: Netherlands
facility: Academ Ziekenhuis Groningen; Medical Oncology
city: Leiden
country: Netherlands
facility: Academisch Ziekenhuis Leiden; Clinical Oncology
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Oslo
country: Norway
facility: The Norvegian Radium Hospital Montebello; Dept of Oncology
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer; Servicio de Oncologia
state: Islas Baleares
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial; Servicio de Hematología y Oncología
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals; Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia
city: Lerida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia; Oncologia Medica
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Linkoeping
country: Sweden
facility: Universitetssjukhuset; Onkologkliniken
city: Lund
country: Sweden
facility: Skånes University Hospital, Skånes Department of Onclology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Lorusso D, Hilpert F, Gonzalez Martin A, Rau J, Ottevanger P, Greimel E, Luck HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastiere-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. doi: 10.1136/ijgc-2019-000370. Epub 2019 Aug 15.