| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced (stage III B-C-IV) ovarian, primary peritoneal and fallopian tube cancer |
| tumore ovarico, primitivo del peritoneo o della tuba di falloppio stadio IIIB-IV (FIGO) |
|
| E.1.1.1 | Medical condition in easily understood language |
| advanced (stage III B-C-IV) ovarian, primary peritoneal and fallopian tube cancer |
| tumore ovarico, primitivo del peritoneo o della tuba di falloppio stadio IIIB-IV (FIGO) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10070907 |
| E.1.2 | Term | Ovarian cancer stage III |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10070908 |
| E.1.2 | Term | Ovarian cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To assess the activity of Carboplatin-Paclitaxel plus Pembrolizumab (MK-3475) in terms of percentage of patients, with advanced ovarian, primary
peritoneal and fallopian tube cancer, who are progression-free after 18
months from the beginning of the first line treatment.
|
Valutare l'attività di pembrolizumab in associazione al trattamento standard di prima linea
con carboplatino e paclitaxel, in termini di pazienti libere da progressione a 18 mesi
dall'inizio del trattamento |
|
| E.2.2 | Secondary objectives of the trial |
(1) To describe PFS of patients receiving Carboplatin-PaclitaxelPembrolizumab.
(2) To describe overall survival (OS) of patients receiving CarboplatinPaclitaxel- Pembrolizumab.
(3) To describe the response rate (RECIST 1.1 criteria) of patients receiving
Carboplatin-Paclitaxel- Pembrolizumab.
(4) To assess the safety and tolerability of Carboplatin-PaclitaxelPembrolizumab in this population.
Exploratory Objectives
(1) To assess patient-reported outcome (PRO) of disease-related symptoms
utilizing the disease-related symptoms – physical (DRS–P) subscale of the
National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index 18 (FOSI-18) Changes and using Euro-Quality of Life 5D (eEQ-5D) tool. (2) To investigate the relationship between PD-L1 expression and response to Pembrolizumabtreatment utilizing newly obtained or archival FFPE tumor tissue.Additional Biomarkers Research |
· Descrivere :
o la Progression Free Survival
o sopravvivenza globale
o tasso di risposte obiettive (RECIST 1.1)
o eventi avversi (CTCAE 4.03)
o i patient reported outcomes tramite gli strumenti FOSI-18 e eEQ-5D
· esplorare:
o la relazione tra l'espressione Immunoistochimica di PD-L1 e la risposta al
trattamento con pembrolizumab
o la relazione di altri biomarcatori (valutazione periferica dei linfociti T; livelli
circolanti di PD-L1 citochine circolanti e tissutali) e la risposta a
pembrolizumab
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Diagnosis/Condition for Entry into the Trial
Patients must have a histologically confirmed diagnosis of advanced (FIGO IIIB-CIV) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients must be
not eligible to receive Bevacizumab in combination with carboplatin and paclitaxel,
due to contraindication, patient refusal or investigator choice.
Subject Inclusion Criteria
1. In order to be eligible for participation in this trial, the subject must:
2. Have a histologically confirmed diagnosis of advanced (FIGO stage IIIB,
IIIC, IV) epithelial ovarian, primary peritoneal or fallopian tube cancer.
3. Have evidence of residual tumor after debulking surgery OR be non-eligible
neither for primary surgery nor for neoadjuvant chemotherapy followed by
interval debulking surgery
4. Be willing and able to provide written informed consent/assent for the trial.
5. Be ³ 18 years of age on day of signing informed consent.
6. Have measurable disease based on RECIST 1.1.
7. Have tumor samples available for biomarker analysis.
8. Have a performance status of 0 or 1 on the ECOG Performance Scale.
9. Female subject of childbearing potential should have a negative urine or
serum pregnancy within 72 hours prior to receiving the first dose of study
medication. If the urine test is positive or cannot be confirmed as negative,
a serum pregnancy test will be required.
10. Female subjects of childbearing potential should be willing to use 2
methods of birth control or be surgically sterile, or abstain from heterosexual
activity for the course of the study through 120 days after the last dose of
study medication. Subjects of childbearing potential are those who have
not been surgically sterilized or have not been free from menses for > 1
year.
11. Must be not eligible to receive Bevacizumab in combination with carboplatin
and paclitaxel, due to contraindication, patient refusal or investigator choice
12. Demonstrate adequate organ function as defined in
Table 1 - Adequate Organ Function Laboratory Values, all screening labs should be performed within 10 days of treatment
initiation. |
Età =18 anni
· Diagnosi istologica di tumore ovarico, primitivo del peritoneo o della tuba di falloppio
stadio IIIB-IV (FIGO)
· Consenso Informato scrittto
· Evidenza di tumore residuo dopo chirurgia primitiva o essere non-eleggibile per
chirurgia citoriduttiva o per chemioterapia neoadiuvante.
· malattia misurabile secondo i criteri RECIST 1.1
· campione tissutale disponibile per le analisi molecolari
· Performance Status ECOG 0 o 1
· Paziente non eleggibile per il trattamento con Bevacizumab a causa di
controindicazioni, rifiuto della paziente, decisione del medico
- Funzione d'organo adeguata, definita come da tabella
· Negatività del test di gravidanza, entro 72 ore dalla prima dose di farmaco, e
disponibilità ad utilizzare 2 metodi contraccettivi o ad astenersi dai rapporti sessuali
per l'intera durata dello studio e fino a 120 giorni dopo l'ultima somministrazione per
donne fertili |
|
| E.4 | Principal exclusion criteria |
1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent or investigational device and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to Pembrolizumab or any of its excipients.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., =Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., =Grade 1 or at baseline) from adverse events due to a previously administered agent.
7. Subjects with =Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
8. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by
imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 28 days
prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
12. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
16. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or other co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or drug specifically targeting T-cell co-stimulation or checkpoint pathways
18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
19. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
20. Has received a live vaccine within 30 days of planned start of study therapy. |
Partecipazione ad altre sperim. cliniche con farmaci sperim. nelle 4
settimane precedenti alla prima somministr. del farmaco in studio
· Diagnosi di immunodeficienza o somministr. di steroidi per via sistemica o
qualsiasi altra forma di terapia immunosoppressiva entro 7 giorni dalla prima
somminis. del farmaco in studio
· Storia conosciuta di Tubercolosi attiva
· Ipersensibilità a pembrolizumab o ad uno dei suoi eccipienti nota
· Terapia con altro anticorpo monoclonale entro le 4 settimane precedenti la prima
somministr. del farmaco in studio o eventi avversi non recuperati (entro il G1
o al livello basale) da precedenti trattamenti antecedenti alle 4 settimane.
· Chemioterapia, radioterapia o piccole molecole ad azione antitumorale nelle 2
settimane precedenti la sommin. del farmaco in studio o eventi avversi
derivanti da tali trattamenti non recuperati (entro il G1 o al livello basale).
· le pazienti con neuropatia = 2 sono eleggibili e rappresentano
un'eccezione al criterio precedente.
· Se chirurgia, la paziente deve aver recuperato completamente da eventuali
complicanze/eventi avversi derivanti dalla chirurgia stessa.
· Altre neoplasie maligne richiedenti trattamento ad eccezione di: carcinoma
basocellulare o squamocellulare della cute che sono stati efficacemente curati,
tumore della cervice uterina in situ
· Presenza di metastasi cerebrali o meningite carcinomatosa nota. Pazienti con
metastasi cerebrali possono essere incluse se le metastasi sono clinicamente
stabili: senza evidenza di progressione radiologica entro le 4 settimane precedenti
la prima somministr. in studio, non sintomatiche (o i cui sintomi sono rientrati
al livello basale entro l'inizio del trattamento sper.), non vi sono nuove
metastasi e non vi è stato utilizzo di steroidi per i 28 giorni precedenti al trattamento
sperim.. Le pazienti con meningite carcinomatosa sono escluse senza
eccezioni.
· Malattie autoimmuni attive che hanno richiesto trattamento sistemico (farmaci
immunosoppressori) nei 2 anni precedenti allo studio. La terapia sostitutiva con
ormoni tiroidei, insulina o corticosteroidi nel caso di insufficienza adrenergica non è
considerata una forma di trattamento sistemico.
· Polmonite non-infettiva attiva o in anamnesi che richiede o ha richiesto il
trattamento con steroidi
· Infezione sistemica attiva richiedente trattamento
· Storia o presenza di condizioni, terapie, anomalie di laboratorio o cliniche
concomitanti che controindichino o interferiscano con la partecipazione della
paziente allo studio.
· Storia di disordini psichiatrici o abuso di sostanze che compromettano la
partecipazione allo studio o la collaborazione dei pazienti.
· Gravidanza o allattamento in corso o previsto per il periodo di tempo tra la visita di
prescreening e il 120 giorno dopo l'ultima somminis. del farmaco
sperimentale
Precedente trattamento con anti-PD1, anti-PD-L1, anti-PD-L2 o altri farmaci aventi
come bersagli molecole co-inibitrici o co-attivanti il linfocita T (e.g. CTLA-4, OX-40,
CD137)
· Storia nota per positività agli anticorpi contro il virus dell'immunodeficienza acquisita
umana (HIV1 o 2)
· Epatite B (HBsAg positività) o Epatite C (HCV RNA qualitativo positivo) attiva nota
· Somministrazione di vaccino vivo entro i 30 giorni precedenti alla data di inizio
studio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| number of subjects who are progression-free after 18 months from the beginning of the first line treatment |
| numero di pazienti libere da progressione a 18 mesi dall'inizio del trattamento |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Imaging assessment should be performed at the end of Cycles 3 and 6, then every 3 cycles (+/- 2 weeks of the scheduled visit) while the patient is receiving Pembrolizumab maintenance, and then at the end of treatment |
.La rivalutazione deve essere eseguita alla fine del ciclo 3 e del ciclo 6 (+/- 2 settimane) poi ogni 3 cicli
durante il mantenimento e poi alla fine del trattamento a dispetto di ogni prolungamento nelle tempistiche dei cicli |
|
| E.5.2 | Secondary end point(s) |
Secondary Objective(s)
(1) To describe PFS of patients receiving Carboplatin-PaclitaxelPembrolizumab.
(2) To describe overall survival (OS) of patients receiving CarboplatinPaclitaxel- Pembrolizumab.
(3) To describe the response rate (RECIST 1.1 criteria) of patients receiving Carboplatin-Paclitaxel- Pembrolizumab.
(4) To assess the safety and tolerability of Carboplatin-PaclitaxelPembrolizumab in this population.
Exploratory Objectives
(1) To assess patient-reported outcome (PRO) of disease-related symptoms utilizing the disease-related symptoms – physical (DRS–P) subscale of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index 18 (FOSI-18) Changes and using Euro-Quality of Life 5D (eEQ-5D) tool.
(2) To investigate the relationship between PD-L1 expression and response to Pembrolizumab treatment utilizing newly obtained or archival FFPE tumor tissue.
Additional Biomarkers Research
1. To investigate the relationship between other biomarkers predicting response to Pembrolizumab treatment using newly obtained or archival FFPE tumor tissue and blood sampling (see pa 12 and 13). |
Obiettivi secondari
· Descrivere :
o la Progression Free Survival
o sopravvivenza globale
o tasso di risposte obiettive (RECIST 1.1)
o eventi avversi (CTCAE 4.03)
o i patient reported outcomes tramite gli strumenti FOSI-18 e eEQ-5D
· esplorare:
o la relazione tra l'espressione Immunoistochimica di PD-L1 e la risposta al
trattamento con pembrolizumab
o la relazione di altri biomarcatori (valutazione periferica dei linfociti T; livelli
circolanti di PD-L1 citochine circolanti e tissutali) e la risposta a
pembrolizumab |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The total estimated duration of the trial is 36 months.
The estimated enrollment period is 16 months. |
| La durata stimata della sperimentazione è di 36 mesi con un periodo di arruolamento di 16 mesi. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
