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Ovarian CancerPhase 3NCT01684878

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

A Phase 3 study testing Gemcitabine (Chemotherapy), Paclitaxel (Chemotherapy) and Pertuzumab in people with Ovarian Cancer, run by Hoffmann-La Roche at 68 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer
What is being tested?
Gemcitabine (Chemotherapy), Paclitaxel (Chemotherapy) and Pertuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
208 participants
Where
68 sitesin 10 countries
Study dates
22 Oct 2012to 28 Apr 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

68 sites in 10 countries.

68 sites in 10 countries

Spain20 sites

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, Barcelona, 08035

  • Hospital Clínic i Provincial; Servicio de Hematología y Oncología

    Barcelona, Barcelona, 08036

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

    Barcelona, Barcelona, 08041

  • Hospital Duran i Reynals; Oncologia

    Barcelona, Barcelona, 08907

  • Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

    Barcelona, Barcelona, 08916

  • Hospital Universitario Reina Sofia; Servicio de Oncologia

    Córdoba, Cordoba, 14004

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

    Girona, Girona, 17007

  • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia

    Lleida, Lerida, 25198

  • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

    Madrid, Madrid, 28007

  • Centro Oncologico MD Anderson Internacional; Servicio de Oncologia

    Madrid, Madrid, 28033

  • Hospital Universitario 12 de Octubre; Servicio de Oncologia

    Madrid, Madrid, 28041

  • Hospital Universitario La Paz; Servicio de Oncologia

    Madrid, Madrid, 28046

  • Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica

    Madrid, Madrid, 28050

  • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

    Málaga, Malaga, 29010

  • Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia

    Murcia, Murcia, 30120

  • Hospital Son Llatzer; Servicio de Oncologia

    Palma de Mallorca, Balearic Islands, 07198

  • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

    Sabadell, Barcelona, 08208

  • Instituto Valenciano Oncologia; Oncologia Medica

    Valencia, Valencia, 46009

  • Hospital Universitario la Fe; Servicio de Oncologia

    Valencia, Valencia, 46026

  • Hospital Universitario Miguel Servet; Servicio Oncologia

    Zaragoza, Zaragoza, 50009

Other trials in Spain

Germany19 sites

  • St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

    Cologne, 50935

  • Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe

    Dresden, 01307

  • Evangelischen Krankenhauses Düsseldorf; Frauenklinik

    Düsseldorf, 40217

  • Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

    Essen, 45122

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

    Essen, 45136

  • Universitätsklinikum Freiburg; Frauenklinik

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum

    Greifswald, 17475

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

    Hamburg, 20246

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

    Hanover, 30177

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

    Heidelberg, 69120

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

    Kiel, 24105

  • Klinikum Konstanz, Frauenklinik

    Konstanz, 78464

  • Klinikum rechts der Isar der TU München; Frauenklinik & Poliklinik

    München, 81675

  • Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

    Offenbach, 63069

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

    Ravensburg, 88212

  • Universitätsfrauen- und Poliklinik am Klinikum Suedstadt

    Rostock, 18059

  • Universitätsklinik Tübingen; Frauenklinik

    Tübingen, 72076

  • Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

    Ulm, 89075

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

    Wiesbaden, 65199

Other trials in Germany

France10 sites

  • Institut Bergonie; Oncologie

    Bordeaux, 33076

  • Centre Francois Baclesse; Oncologie

    Caen, 14076

  • Centre Georges Francois Leclerc; Oncologie 3

    Dijon, 21079

  • CRLCC Val dAurelle Paul Lam

    Montpellier, 34298

  • Hopital Tenon; Oncologie Radiotherapie

    Paris, 75970

  • Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont

    Pierre-Bénite, 69310

  • Clinique Armoricaine Radiologie; Hopital de Jour

    Plérin, 22190

  • Ico Rene Gauducheau; Oncologie

    Saint-Herblain, 44805

  • Centre Alexis Vautrin; Oncologie Medicale

    Vandœuvre-lès-Nancy, 54511

  • Institut Gustave Roussy; Oncologie Medicale

    Villejuif, 94800

Other trials in France

Italy7 sites

  • A.O.Spedali Civili; Ostetricia e Ginecologia

    Brescia, Lombardy, 25123

  • Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica

    Genoa, Liguria, 16128

  • Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica

    Milan, Lombardy, 20133

  • Istituto Europeo Di Oncologia

    Milan, Lombardy, 20141

  • Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica

    Naples, Campania, 80131

  • A.O.U Pisana; Dipartimento di Ginecologia Oncologica

    Pisa, Tuscany, 56126

  • Istituto Regina Elena; Oncologia Medica A

    Rome, Lazio, 00168

Other trials in Italy

Netherlands4 sites

  • Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam, 1066 CX

  • Academ Ziekenhuis Groningen; Medical Oncology

    Groningen, 9713 GZ

  • Academisch Ziekenhuis Leiden; Clinical Oncology

    Leiden, 2333 ZA

  • UMC St Radboud

    Nijmegen, 6525 GA

Other trials in Netherlands

Austria2 sites

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

    Innsbruck, 6020

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

    Vienna, 1090

Other trials in Austria

Denmark2 sites

  • Herlev Hospital; Onkologisk afdeling

    Herlev, 2730

  • Rigshospitalet, Onkologisk Klinik

    København Ø, 2100

Other trials in Denmark

Sweden2 sites

  • Universitetssjukhuset; Onkologkliniken

    Linköping, 58185

  • Skånes University Hospital, Skånes Department of Onclology

    Lund, 22185

Other trials in Sweden

Belgium1 site

  • UZ Leuven Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Norway1 site

  • The Norvegian Radium Hospital Montebello; Dept of Oncology

    Oslo, 0379

Other trials in Norway

About this study

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

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
Being tested
Gemcitabine (Chemotherapy), Paclitaxel (Chemotherapy), Pertuzumab, Placebo, Topotecan (Chemotherapy)
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • 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.

  • PertuzumabDrug

    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.

  • PlaceboDrug

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

  • 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.

Study groups in NCT01684878
Study groupRoleWhat they receive
Part 1: Pertuzumab + TopotecanExperimentalParticipants received pertuzumab and topotecan in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
Receives: Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Topotecan (Chemotherapy)
Part 1: Pertuzumab + PaclitaxelExperimentalParticipants received pertuzumab and paclitaxel in cycles of 3 weeks until progressive disease as per investigator's assessment, unacceptable toxicity, withdrawal of consent, or death.
Receives: Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Placebo
Part 2: Pertuzumab+ChemotherapyExperimentalParticipants 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.
Receives: Drug: Gemcitabine (Chemotherapy); Drug: Paclitaxel (Chemotherapy); Drug: Pertuzumab; Drug: Topotecan (Chemotherapy)
Part 2: Placebo+ChemotherapyPlacebo comparatorParticipants 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.
Receives: Drug: Gemcitabine (Chemotherapy); Drug: Paclitaxel (Chemotherapy); Drug: Placebo; Drug: Topotecan (Chemotherapy)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (7)

  1. Part 1- Objective Response Rate (ORR)

    ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

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

  2. Part 2- Objective Response Rate (ORR)

    ORR was defined as the number of participants with BOR of CR or PR recorded from the start of treatment, until the end of treatment. BOR documented as confirmed CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

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

  3. Part 1: PFS Assessed by the Investigator

    PFS as assessed by Investigator was defined as the time from first dose of pertuzumab or chemotherapy in Part 1 of the trial, until disease progression according to RECIST version 1.1, symptomatic deterioration or death from any cause, whichever occurs first. 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. Participants were censored at the last tumor assessment. Participants who have no tumor assessments after baseline and who were still alive will be censored at 1 day.

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

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

    PFS (Investigator-assessed) is defined as the time from randomization, until disease progression according to RECIST v1.1 including death or MBO, whichever occurs first. Censoring is based on the last tumor assessment. If no tumor assessment post baseline, then censoring is at day 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.

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

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

    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scores, a higher score represents a more severe level of symptoms. For the global health status scores, a higher score represents a better quality of life.

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

  6. Part 2: 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.

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

  7. Part 2: Overall Survival

    Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2012 (estimated)
  2. Study start22 Oct 2012
  3. Primary completion30 Jan 2015
  4. Study completion28 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
208 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01684878
Sponsor's protocol ID
MO28113
Other IDs
2011-005975-17
Status last verified
Apr 2017
First submitted
11 Sep 2012
Last updated
23 May 2017

Publications

  • 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.

    PubMed 31420414

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gemcitabine (Chemotherapy), Paclitaxel (Chemotherapy) and Pertuzumab in people with Ovarian Cancer, run by Hoffmann-La Roche at 68 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 sites in Spain, Germany, France, Italy, Netherlands and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Percentage of Participants With Adverse Events (AEs) (time frame: Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01684878, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2017.

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