Pertuzumab in Platinum-Resistant Low Human Epidermal Growth Factor Receptor 3 (HER3) Messenger Ribonucleic Acid (mRNA) Epithelial Ovarian Cancer (PENELOPE)
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT01684878
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 208
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: Pertuzumab+Chemotherapy Paclitaxel (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. Part 1: Pertuzumab + Paclitaxel Paclitaxel (Chemotherapy) 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. Part 1: Pertuzumab + Topotecan Paclitaxel (Chemotherapy) 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. Part 2: Placebo+Chemotherapy Gemcitabine (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. Part 1: Pertuzumab + Topotecan Topotecan (Chemotherapy) 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. Part 1: Pertuzumab + Paclitaxel Placebo 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. Part 2: Pertuzumab+Chemotherapy Gemcitabine (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. Part 2: Pertuzumab+Chemotherapy Topotecan (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. Part 2: Placebo+Chemotherapy Placebo 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. Part 2: Placebo+Chemotherapy Paclitaxel (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. Part 2: Placebo+Chemotherapy Topotecan (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. Part 1: Pertuzumab + Paclitaxel Pertuzumab 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. Part 1: Pertuzumab + Topotecan Pertuzumab 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. Part 2: Pertuzumab+Chemotherapy Pertuzumab 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.
- Primary Outcome Measures
Name Time Method Part 1: Percentage of Participants With Adverse Events (AEs) Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment) 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.
Part 2: Progression Free Survival (PFS) as Assessed by a Blinded Independent Review Committee (IRC) Including Malignant Bowel Obstruction (MBO) Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) 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.
- Secondary Outcome Measures
Name Time Method Part 2: Overall Survival Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) Overall survival was defined as the time from randomization into Part 2 of the trial until death from any cause
Part 1- Objective Response Rate (ORR) Approximately 28 months (assessed at baseline and every 9 weeks from randomization until disease progression) 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.
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) 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.
Part 2- Objective Response Rate (ORR) Approximately 44 months (assessed at screening and every 9 weeks from randomization until disease progression) 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.
Part 1: PFS Assessed by the Investigator Approximately 28 months (assessed at screening and every 9 weeks from randomization until disease progression) 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.
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) 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.
Part 2: Percentage of Participants With Adverse Events (AEs) Approximately 28 months (assessed at screening, baseline until 28 days after the last dose of study treatment) 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.
Trial Locations
- Locations (68)
Academ Ziekenhuis Groningen; Medical Oncology
🇳🇱Groningen, Netherlands
Academisch Ziekenhuis Leiden; Clinical Oncology
🇳🇱Leiden, Netherlands
UMC St Radboud
🇳🇱Nijmegen, Netherlands
Herlev Hospital; Onkologisk afdeling
🇩🇰Herlev, Denmark
Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie
🇦🇹Wien, Austria
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie
🇦🇹Innsbruck, Austria
Centre Francois Baclesse; Oncologie
🇫🇷Caen, France
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Universitätsklinikum Essen; Zentrum Für Frauenheilkunde
🇩🇪Essen, Germany
Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum
🇩🇪Greifswald, Germany
Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding
🇩🇪Hannover, Germany
Ente Ospedaliero Ospedali Galliera; S.C. Oncologia Medica
🇮🇹Genova, Liguria, Italy
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
UNI-Klinikum Campus Kiel Klinik f.Gynäkologie u.Geburtshilfe
🇩🇪Kiel, Germany
Klinikum rechts der Isar der TU München; Frauenklinik & Poliklinik
🇩🇪München, Germany
Hospital Son Llatzer; Servicio de Oncologia
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Centre Alexis Vautrin; Oncologie Medicale
🇫🇷Vandoeuvre Les Nancy, France
Institut Gustave Roussy; Oncologie Medicale
🇫🇷Villejuif, France
A.O.Spedali Civili; Ostetricia e Ginecologia
🇮🇹Brescia, Lombardia, Italy
Hopital Tenon; Oncologie Radiotherapie
🇫🇷Paris, France
Institut Bergonie; Oncologie
🇫🇷Bordeaux, France
St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe
🇩🇪Koeln, Germany
Klinikum Konstanz, Frauenklinik
🇩🇪Konstanz, Germany
The Norvegian Radium Hospital Montebello; Dept of Oncology
🇳🇴Oslo, Norway
Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
🇪🇸Sabadell, Barcelona, Spain
Ch Lyon Sud; Chir Onc Gyne Sct Jules Courmont
🇫🇷Pierre Benite, France
Clinique Armoricaine Radiologie; Hopital de Jour
🇫🇷Plerin, France
Kliniken Essen-Mitte Evang. Huyssens-Stiftung, Klinik für Gynäkologie und gynäkologische Onkologie
🇩🇪Essen, Germany
Universitätsklinikum Freiburg; Frauenklinik
🇩🇪Freiburg, Germany
Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe
🇩🇪Offenbach, Germany
Hämatologisch/Onkologische Praxis Dr. Herbrick - Zipp/Prof. Dr. Decker, Studienzentrum
🇩🇪Ravensburg, Germany
Universitätsfrauen- und Poliklinik am Klinikum Suedstadt
🇩🇪Rostock, Germany
A.O.U Pisana; Dipartimento di Ginecologia Oncologica
🇮🇹Pisa, Toscana, Italy
Antoni van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Rigshospitalet, Onkologisk Klinik
🇩🇰København Ø, Denmark
CRLCC Val dAurelle Paul Lam
🇫🇷Montpellier cedex 5, France
Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe
🇩🇪Dresden, Germany
Evangelischen Krankenhauses Düsseldorf; Frauenklinik
🇩🇪Düsseldorf, Germany
Universitätsklinikum Hamburg-Eppendorf (UKE); Klinik und Poliklinik für Gynäkologie
🇩🇪Hamburg, Germany
Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitätsklinik Tübingen; Frauenklinik
🇩🇪Tübingen, Germany
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie
🇩🇪Wiesbaden, Germany
Universitätsklinikum Ulm Am Michelsberg; Frauenklinik
🇩🇪Ulm, Germany
Istituto Regina Elena; Oncologia Medica A
🇮🇹Roma, Lazio, Italy
Istituto Tumori Napoli;Unità Operativa Oncologia Medica Uro-Ginecologica
🇮🇹Napoli, Campania, Italy
Istituto Nazionale dei Tumori; Divisione Oncologia Chirurgica e Ginecologica
🇮🇹Milano, Lombardia, Italy
Istituto Europeo Di Oncologia
🇮🇹Milano, Lombardia, Italy
Hospital ClÃnic i Provincial; Servicio de HematologÃa y OncologÃa
🇪🇸Barcelona, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Duran i Reynals; Oncologia
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia; Servicio de Oncologia
🇪🇸Cordoba, Spain
Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
🇪🇸Lerida, Spain
Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia
🇪🇸Girona, Spain
Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
🇪🇸Malaga, Spain
Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
🇪🇸Murcia, Spain
Instituto Valenciano Oncologia; Oncologia Medica
🇪🇸Valencia, Spain
Hospital Universitario la Fe; Servicio de Oncologia
🇪🇸Valencia, Spain
Skånes University Hospital, Skånes Department of Onclology
🇸🇪Lund, Sweden
Universitetssjukhuset; Onkologkliniken
🇸🇪Linkoeping, Sweden
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸Zaragoza, Spain
Centro Oncologico MD Anderson Internacional; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
🇪🇸Madrid, Spain