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Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43)

Studio Clinico

Patologia: Tumori dell’ovaio

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
- Has just completed primary debulking surgery or is eligible for primary or interval debulking surgery
- Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
- Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125) (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
- Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and - Programmed Cell Death-Ligand 1 (PD-L1) tumor markers status prior to randomization
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the lead-in period and within 7 days prior to randomization
- Is not pregnant, not breastfeeding, and 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered)
- Has adequate organ function

Criteri di esclusione: 

- Has hypersensitivity to docetaxel or polysorbate 80

Numero di pazienti previsti: 

1086

Schema di trattamento: 

Following a lead-in period during which all participants receive a single 3-week cycle of carboplatin/paclitaxel, participants will be randomly assigned in to one of three treatment arms:

- Pembrolizumab+Olaparib,
- Pembrolizumab+Placebo for Olaparib, or
- Placebo for Pembrolizumab+Placebo for Olaparib.

At Investigator's discretion and prior to participant randomization, one of the following carboplatin/paclitaxel regimens is to be selected:

- up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle
- up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND paclitaxel 80 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle; or
- up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle.

Trattamento sperimentale: 

Pembrolizumab + Olaparib + SoC

Trattamento di controllo: 

SoC

Obiettivi primari dello studio: 

- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 6 years ]
PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by the Investigator will be presented.

- Overall Survival (OS) [ Time Frame: Up to approximately 6 years ]
OS is defined as the time from the date of randomization to death due to any cause. The OS will be presented

Obiettivi secondari dello studio: 

- PFS Per RECIST 1.1 As Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 6 years ]
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review will be presented.

- PFS After Next-line Treatment (PFS2) Following Discontinuation of Study Treatment As Assessed by the Investigator [ Time Frame: Up to approximately 78 months ]
PFS2 is defined as the time from randomization until PD on next-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be presented.

- Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 73 months ]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

- Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 6 years ]
The number of participants who discontinue study treatment due to an AE will be presented.

- Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Using Questions from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) [ Time Frame: Baseline and End of Study Participation (Up to approximately 6 years) ]
Participants are asked to answer 2 questions from the EORTC QLQ-C30 about their GHS: 'How would you rate your overall health during the past week?'and 'How would you rate your overall quality of life during the past week?' Responses are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status. The change from baseline in GHS/QoL score of participants will be presented.

- Change from Baseline in Abdominal and Gastrointestinal (Abdominal/GI) Symptoms Score Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale [ Time Frame: Baseline and End of Study Participation (Up to approximately 6 years) ]
Participants are asked to answer 6 questions from the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28) abdominal/GI symptom scale about abdominal pain, bloated feeling in abdomen/stomach, changes in clothing fit, changes in bowel habit, flatulence and stomach fullness when eating. Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better abdominal/GI symptoms. The change from baseline in abdominal/GI symptom score of participants will be presented.

- Time to First Subsequent Anti-cancer Treatment (TFST) [ Time Frame: Up to approximately 6 years ]
TFST is defined as the time from randomization to initiation of first subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TFST will be presented.

- Time to Second Subsequent Anti-cancer Treatment (TSST) [ Time Frame: Up to approximately 6 years ]
TSST is defined as the time from randomization to initiation of second subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TSST will be presented.

- Time to Discontinuation of Study Treatment or Death (TDT) [ Time Frame: Up to approximately 6 years ]
TDT is defined as the time from the date of randomization to discontinuation of study treatment or death due to any cause, whichever occurs first. The TDT will be presented.

- Pathological Complete Response (pCR) Rate [ Time Frame: Up to approximately 30 months ]
pCR is defined as all surgical specimens collected during the interval debulking surgery are microscopically negative for malignancy. The pCR rate for all surgical specimens will be presented.

- Time Without Symptom of Disease Progression or Toxicity of Treatment (TWiST) [ Time Frame: Up to approximately 6 years ]
TWiST is defined as the time from randomization to disease progression or treatment-related toxicity, whichever occurs first. The TWiST will be presented.

Data di inizio dell'arruolamento: 30.01.2019

Data di fine dell'arruolamento: 11.01.2021

Centri partecipanti

Nord Italia

ASST Lecco - PO Alessandro Manzoni
Via Dell'Eremo 9 - 23900 Lecco - LC

 

Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI

Riferimento: Prof.ssa Nicoletta Colombo
Telefono: 0257489543
Email: nicoletta.colombo@ieo.it

 

Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD

 

Ospedale S. Anna
Corso Spezia 60 - 10126 Torino - TO
Città della Salute e della Scienza. NB: Lo studio non è ancora attivo

 

Presidio ospedaliero di Santa Chiara
Largo Medaglie d'Oro 1 - 38122 Trento - TN

 

Azienda Ospedaliera Santa Maria della Misericordia
Piazzale Santa Maria della Misericordia 15 - 33100 Udine - UD

 

Centro Italia

Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM

 

Università La Sapienza Policlinico Umberto I
Viale del Policlinico 155 - 00161 Roma - RM
NB: Lo studio non è ancora attivo

 

Sud Italia e isole

Istituto Tumori “Giovanni Paolo II” IRCCS
Viale Orazio Flacco 65 - 70124 Bari - BA

 

Ospedale Sacro cuore di Gesù - Fatebenefratelli
Viale Principe di Napoli 14/A - 82100 Benevento - BN

 

A.O. per l’Emergenza Cannizzaro di Catania
Via Messina 829 - 95126 Catania - CT
NB: Lo studio non è ancora attivo

 

Azienda Ospedaliera Universitaria Federico II
Via Sergio Pansini 5 - 80131 Napoli - NA

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2018-001973-25

Data di inserimento: 18.09.2019

Promotore

Merck Sharp & Dohme Corp

CRO

NA

Principal Investigator ITALIA

Istituto Europeo di Oncologia, Milano

Riferimento: Prof.ssa Nicoletta Colombo

Telefono: 0257489543

Email: nicoletta.colombo@ieo.it

Localita: Milano

 

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