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

NCT01684878 | Completed Phase 3 Results

• 2 other identifiers: MO281132011-005975-17
• Study Type: interventional
• Target: 208
• Locations: 10 countries
• Sites: 68

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).

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Part 1: Percentage of Participants With Adverse Events (AEs)

  An AE can be any unfavorable and unintended sign (including an abnormality laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)

• Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO)

  PFS (IRC-Assessed) was defined as the time from randomization into Part 2 of the trial until progressive disease (PD), MBO or death from any cause, whichever occurred first per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD could base on symptom deterioration or was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions and/or the unequivocal progression of existing non-target lesions.

  Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

Secondary Outcomes (7)

• Part 1- Objective Response Rate (ORR)

  Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression)

• Part 2- Objective Response Rate (ORR)

  Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

• Part 1: PFS Assessed by the Investigator

  Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression)

• Part 2: Progression-free Survival (PFS) Assessed by the Investigator

  Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression)

• Part 2: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire (QLQ) of Core 30 (C30) Score

  Baseline (assessed at baseline and every 9 weeks from randomization until disease progression)

Study Arms (4)

Part 1: Pertuzumab + Topotecan

EXPERIMENTAL

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.

Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Topotecan (Chemotherapy)

Part 1: Pertuzumab + Paclitaxel

EXPERIMENTAL

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.

Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Placebo

Part 2: Pertuzumab+Chemotherapy

EXPERIMENTAL

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.

Drug: Gemcitabine (Chemotherapy); Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Topotecan (Chemotherapy)

Part 2: Placebo+Chemotherapy

PLACEBO COMPARATOR

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.

Drug: Gemcitabine (Chemotherapy); Drug: Paclitaxel (Chemotherapy); Drug: Placebo; Drug: Topotecan (Chemotherapy)

Interventions

Gemcitabine (Chemotherapy) 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.

Part 2: Pertuzumab+Chemotherapy; Part 2: Placebo+Chemotherapy

Paclitaxel (Chemotherapy) 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.

Part 1: Pertuzumab + Paclitaxel; Part 1: Pertuzumab + Topotecan; Part 2: Pertuzumab+Chemotherapy; Part 2: Placebo+Chemotherapy

Pertuzumab 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.

Part 1: Pertuzumab + Paclitaxel; Part 1: Pertuzumab + Topotecan; Part 2: Pertuzumab+Chemotherapy

Placebo DRUG

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

Part 1: Pertuzumab + Paclitaxel; Part 2: Placebo+Chemotherapy

Topotecan (Chemotherapy) 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 + Topotecan; Part 2: Pertuzumab+Chemotherapy; Part 2: Placebo+Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (68)

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

Innsbruck, 6020, Austria

Location

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

Vienna, 1090, Austria

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Herlev Hospital; Onkologisk afdeling

Herlev, 2730, Denmark

Location

Rigshospitalet, Onkologisk Klinik

København Ø, 2100, Denmark

Location

Institut Bergonie; Oncologie

Bordeaux, 33076, France

Location

Centre Francois Baclesse; Oncologie

Caen, 14076, France

Location

Centre Georges Francois Leclerc; Oncologie 3

Dijon, 21079, France

Location

CRLCC Val dAurelle Paul Lam

Montpellier, 34298, France

Location

Hopital Tenon; Oncologie Radiotherapie

Paris, 75970, France

Location

Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont

Pierre-Bénite, 69310, France

Location

Clinique Armoricaine Radiologie; Hopital de Jour

Plérin, 22190, France

Location

Ico Rene Gauducheau; Oncologie

Saint-Herblain, 44805, France

Location

Centre Alexis Vautrin; Oncologie Medicale

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy; Oncologie Medicale

Villejuif, 94800, France

Location

St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

Cologne, 50935, Germany

Location

Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe

Dresden, 01307, Germany

Location

Evangelischen Krankenhauses Düsseldorf; Frauenklinik

Düsseldorf, 40217, Germany

Location

Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

Essen, 45122, Germany

Location

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

Essen, 45136, Germany

Location

Universitätsklinikum Freiburg; Frauenklinik

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum

Greifswald, 17475, Germany

Location

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

Hamburg, 20246, Germany

Location

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

Hanover, 30177, Germany

Location

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

Heidelberg, 69120, Germany

Location

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

Kiel, 24105, Germany

Location

Klinikum Konstanz, Frauenklinik

Konstanz, 78464, Germany

Location

Klinikum rechts der Isar der TU München; Frauenklinik & Poliklinik

München, 81675, Germany

Location

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

Offenbach, 63069, Germany

Location

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

Ravensburg, 88212, Germany

Location

Universitätsfrauen- und Poliklinik am Klinikum Suedstadt

Rostock, 18059, Germany

Location

Universitätsklinik Tübingen; Frauenklinik

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

Ulm, 89075, Germany

Location

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

Wiesbaden, 65199, Germany

Location

Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica

Napoli, Campania, 80131, Italy

Location

Istituto Regina Elena; Oncologia Medica A

Rome, Lazio, 00168, Italy

Location

Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica

Genoa, Liguria, 16128, Italy

Location

A.O.Spedali Civili; Ostetricia e Ginecologia

Brescia, Lombardy, 25123, Italy

Location

Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica

Milan, Lombardy, 20133, Italy

Location

Istituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

A.O.U Pisana; Dipartimento di Ginecologia Oncologica

Pisa, Tuscany, 56126, Italy

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Academ Ziekenhuis Groningen; Medical Oncology

Groningen, 9713 GZ, Netherlands

Location

Academisch Ziekenhuis Leiden; Clinical Oncology

Leiden, 2333 ZA, Netherlands

Location

UMC St Radboud

Nijmegen, 6525 GA, Netherlands

Location

The Norvegian Radium Hospital Montebello; Dept of Oncology

Oslo, 0379, Norway

Location

Hospital Son Llatzer; Servicio de Oncologia

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, Barcelona, 08036, Spain

Location

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

Barcelona, Barcelona, 08041, Spain

Location

Hospital Duran i Reynals; Oncologia

Barcelona, Barcelona, 08907, Spain

Location

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Barcelona, Barcelona, 08916, Spain

Location

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

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

Girona, Girona, 17007, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

Lleida, Lerida, 25198, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, Madrid, 28007, Spain

Location

Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

Madrid, Madrid, 28033, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, Madrid, 28041, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, Madrid, 28046, Spain

Location

Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

Madrid, Madrid, 28050, Spain

Location

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

Málaga, Malaga, 29010, Spain

Location

Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia

Murcia, Murcia, 30120, Spain

Location

Instituto Valenciano Oncologia; Oncologia Medica

Valencia, Valencia, 46009, Spain

Location

Hospital Universitario la Fe; Servicio de Oncologia

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, Zaragoza, 50009, Spain

Location

Universitetssjukhuset; Onkologkliniken

Linköping, 58185, Sweden

Location

Skånes University Hospital, Skånes Department of Onclology

Lund, 22185, Sweden

Location

Related Publications (1)

• 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.

  PMID: 31420414 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Gemcitabine; Drug Therapy; Paclitaxel; pertuzumab; Topotecan

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: September 13, 2012
• Study Start: October 22, 2012
• Primary Completion: January 30, 2015
• Study Completion: April 28, 2016
• Last Updated: May 23, 2017
• Results First Posted: November 23, 2016

Record last verified: 2017-04

Locations

FR (10); IT (7); NL (4); ES (20); BE (1); SE (2); NO (1); DE (19); AU (2); DK (2)