Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)

NCT ID: NCT01684878

Last Updated: 2017-05-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

208 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-22

Study Completion Date

2016-04-28

Brief Summary

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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).

Detailed Description

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Conditions

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Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Part 1: Pertuzumab + Topotecan

Participants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.

Group Type EXPERIMENTAL

Paclitaxel (Chemotherapy)

Intervention Type DRUG

Participants administered paclitaxel at a dosage of 80 mg/m\^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.

Pertuzumab

Intervention Type DRUG

Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.

Topotecan (Chemotherapy)

Intervention Type DRUG

Participants administered topotecan at a dosage of 1.25 mg/m\^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.

Part 1: Pertuzumab + Paclitaxel

Participants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.

Group Type EXPERIMENTAL

Paclitaxel (Chemotherapy)

Intervention Type DRUG

Participants administered paclitaxel at a dosage of 80 mg/m\^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.

Pertuzumab

Intervention Type DRUG

Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.

Placebo

Intervention Type DRUG

Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.

Part 2: Pertuzumab+Chemotherapy

Participants received pertuzumab and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.

Group Type EXPERIMENTAL

Gemcitabine (Chemotherapy)

Intervention Type DRUG

Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.

Paclitaxel (Chemotherapy)

Intervention Type DRUG

Participants administered paclitaxel at a dosage of 80 mg/m\^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.

Pertuzumab

Intervention Type DRUG

Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.

Topotecan (Chemotherapy)

Intervention Type DRUG

Participants administered topotecan at a dosage of 1.25 mg/m\^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.

Part 2: Placebo+Chemotherapy

Participants received pertuzumab matching placebo and chemotherapy (paclitaxel or topotecan or gemcitabine) in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death. Chemotherapy was administered as per investigators discretion.

Group Type PLACEBO_COMPARATOR

Gemcitabine (Chemotherapy)

Intervention Type DRUG

Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.

Paclitaxel (Chemotherapy)

Intervention Type DRUG

Participants administered paclitaxel at a dosage of 80 mg/m\^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.

Placebo

Intervention Type DRUG

Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.

Topotecan (Chemotherapy)

Intervention Type DRUG

Participants administered topotecan at a dosage of 1.25 mg/m\^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.

Interventions

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Gemcitabine (Chemotherapy)

Participants administered gemcitabine at a dosage of 1000 milligrams per square meter (mg/m\^2) intravenous (IV) infusion on Days 1 and 8 every 3 weeks.

Intervention Type DRUG

Paclitaxel (Chemotherapy)

Participants administered paclitaxel at a dosage of 80 mg/m\^2 as 1 hour IV infusion on Days 1, 8 and 15 every 3 weeks.

Intervention Type DRUG

Pertuzumab

Participants administered pertuzumab 840 milligrams (mg) IV infusion on Day 1 of the first treatment cycle as a loading dose, followed by 420 mg on Day 1 of each subsequent 3 weekly cycle.

Intervention Type DRUG

Placebo

Participants administered pertuzumab matching placebo IV infusion on Day 1 of each 3 weekly cycle.

Intervention Type DRUG

Topotecan (Chemotherapy)

Participants administered topotecan at a dosage of 1.25 mg/m\^2 as a 30 minute IV infusion daily on Days 1 to 5 every 3 weeks.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie

Innsbruck, , Austria

Site Status

Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie

Vienna, , Austria

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

Herlev Hospital; Onkologisk afdeling

Herlev, , Denmark

Site Status

Rigshospitalet, Onkologisk Klinik

København Ø, , Denmark

Site Status

Institut Bergonie; Oncologie

Bordeaux, , France

Site Status

Centre Francois Baclesse; Oncologie

Caen, , France

Site Status

Centre Georges Francois Leclerc; Oncologie 3

Dijon, , France

Site Status

CRLCC Val dAurelle Paul Lam

Montpellier, , France

Site Status

Hopital Tenon; Oncologie Radiotherapie

Paris, , France

Site Status

Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont

Pierre-Bénite, , France

Site Status

Clinique Armoricaine Radiologie; Hopital de Jour

Plérin, , France

Site Status

Ico Rene Gauducheau; Oncologie

Saint-Herblain, , France

Site Status

Centre Alexis Vautrin; Oncologie Medicale

Vandœuvre-lès-Nancy, , France

Site Status

Institut Gustave Roussy; Oncologie Medicale

Villejuif, , France

Site Status

St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

Cologne, , Germany

Site Status

Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe

Dresden, , Germany

Site Status

Evangelischen Krankenhauses Düsseldorf; Frauenklinik

Düsseldorf, , Germany

Site Status

Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

Essen, , Germany

Site Status

Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gynäkologische Onkologie

Essen, , Germany

Site Status

Universitätsklinikum Freiburg; Frauenklinik

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum

Greifswald, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie

Hamburg, , Germany

Site Status

Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding

Hanover, , Germany

Site Status

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

Heidelberg, , Germany

Site Status

UNI-Klinikum Campus Kiel Klinik f.Gynäkologie u.Geburtshilfe

Kiel, , Germany

Site Status

Klinikum Konstanz, Frauenklinik

Konstanz, , Germany

Site Status

Klinikum rechts der Isar der TU München; Frauenklinik & Poliklinik

München, , Germany

Site Status

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

Offenbach, , Germany

Site Status

Hämatologisch/Onkologische Praxis Dr. Herbrick - Zipp/Prof. Dr. Decker, Studienzentrum

Ravensburg, , Germany

Site Status

Universitätsfrauen- und Poliklinik am Klinikum Suedstadt

Rostock, , Germany

Site Status

Universitätsklinik Tübingen; Frauenklinik

Tübingen, , Germany

Site Status

Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

Ulm, , Germany

Site Status

HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie

Wiesbaden, , Germany

Site Status

Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica

Napoli, Campania, Italy

Site Status

Istituto Regina Elena; Oncologia Medica A

Rome, Lazio, Italy

Site Status

Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica

Genoa, Liguria, Italy

Site Status

A.O.Spedali Civili; Ostetricia e Ginecologia

Brescia, Lombardy, Italy

Site Status

Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica

Milan, Lombardy, Italy

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Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Site Status

A.O.U Pisana; Dipartimento di Ginecologia Oncologica

Pisa, Tuscany, Italy

Site Status

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Site Status

Academ Ziekenhuis Groningen; Medical Oncology

Groningen, , Netherlands

Site Status

Academisch Ziekenhuis Leiden; Clinical Oncology

Leiden, , Netherlands

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UMC St Radboud

Nijmegen, , Netherlands

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The Norvegian Radium Hospital Montebello; Dept of Oncology

Oslo, , Norway

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Hospital Son Llatzer; Servicio de Oncologia

Palma de Mallorca, Balearic Islands, Spain

Site Status

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Barcelona, Spain

Site Status

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, Barcelona, Spain

Site Status

Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia

Barcelona, Barcelona, Spain

Site Status

Hospital Duran i Reynals; Oncologia

Barcelona, Barcelona, Spain

Site Status

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Barcelona, Barcelona, Spain

Site Status

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain

Site Status

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

Site Status

Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia

Girona, Girona, Spain

Site Status

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

Lleida, Lerida, Spain

Site Status

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, Madrid, Spain

Site Status

Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

Madrid, Madrid, Spain

Site Status

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Madrid, Spain

Site Status

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, Madrid, Spain

Site Status

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, Madrid, Spain

Site Status

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

Málaga, Malaga, Spain

Site Status

Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia

Murcia, Murcia, Spain

Site Status

Instituto Valenciano Oncologia; Oncologia Medica

Valencia, Valencia, Spain

Site Status

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, Valencia, Spain

Site Status

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, Zaragoza, Spain

Site Status

Universitetssjukhuset; Onkologkliniken

Linköping, , Sweden

Site Status

Skånes University Hospital, Skånes Department of Onclology

Lund, , Sweden

Site Status

Countries

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Austria Belgium Denmark France Germany Italy Netherlands Norway Spain Sweden

References

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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.

Reference Type DERIVED
PMID: 31420414 (View on PubMed)

Other Identifiers

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2011-005975-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO28113

Identifier Type: -

Identifier Source: org_study_id

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