ServiziMenu principale

<< Torna a "Tutti gli studi"

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)

Studio Clinico

Patologia: Tumori del rene

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Adiuvante/neoadiuvante

Criteri di inclusione: 

Type of Participant and Disease Characteristics
1. Must have histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features. Diagnosis of RCC with clear cell component is to be made by the investigator and does not require central histology review.
Demographics
2. Be ≥ 18 years of age on day of signing informed consent.
Female Participants:
3. Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
4. Female participants of childbearing potential must be willing to use an adequate method of contraception as outlined in Appendix 5, for the course of the trial through 120 days after the last dose of trial drug.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
Male Participants:
5. Male participants of childbearing potential must agree to use an adequate method of contraception as outlined in Appendix 5, starting with the first dose of trial therapy through 120 days after the last dose of trial therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
Informed Consent
6. The participant provides written informed consent/assent for the trial. The participant may also provide consent/assent for Future Biomedical Research; however the participant may participate in the main trial without participating in Future Biomedical Research.
Other Inclusion Criteria
7. Have intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
a) Intermediate-high risk RCC
- pT2, Gr. 4 or sarcomatoid, N0, M0
- pT3, Any Gr., N0, M0
b) High risk RCC
- pT4, Any Gr. N0, M0
- pT Any stage, Any Gr., N+, M0
c) M1 NED RCC (participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy)
8. Have received no prior systemic therapy for advanced RCC (except nephrectomy or metastasectomy).
9. Have undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of metastatic lesion(s) in M1 NED participants) with negative surgical margins.
10. Must have undergone a nephrectomy (and metastasectomy for M1 NED) ≥28 days prior to signing informed consent and must be randomized ≤12 weeks after surgery.
11. Must be tumor-free as assessed by the Investigator and validated by either CT or MRI scan of the brain and CAP and a bone scan ≤28 days from randomization. All baseline
scans must be sent to the central imaging vendor and receipt must be confirmed prior to randomization.
12. Have provided adequate tissue from the primary tumor (and resected metastatic lesion for M1 NED participants). Adequacy of the samples for biomarker analysis will be evaluated by a central laboratory.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date the slides are cut (details pertaining to tumor tissue submission and guidelines for tissue adequacy can be found in the Procedure Manual).
13. Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
14. Have adequate organ function. Specimens must be collected within 10 days prior to randomization.

 

Criteri di esclusione: 

Medical Conditions
1. Has had major surgery, other than nephrectomy plus resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization.
Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
2. Has received prior radiotherapy for RCC.
3. Has residual thrombus post nephrectomy in the vena renalis or vena cava.
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
5. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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) is not considered a form of systemic treatment and is allowed.
6. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in
situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy.
7. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
8. Has an active infection requiring systemic therapy.
9. Has a known history of human immunodeficiency virus infection. No human immunodeficiency virus testing is required unless mandated by local health authority.
10. Has a known active hepatitis B (hepatitis B surface antigen reactive) or hepatitis C virus (eg, hepatitis C virus [HCV] RNA [qualitative] is detected).
Note: HCV RNA testing is not required in those countries where local standard of care uses only Hepatitis C antibody testing as evidence of status of Hepatitis C.
11. Has a known history of active tuberculosis (Bacillus tuberculosis).
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial in the opinion of the investigator.
14. Has had a prior solid organ transplant.
15. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients (refer to Investigator’s Brochure for further details on excipients).
16. A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours before randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be
excluded/discontinued from the trial in the event of a positive or borderline positive test result.
17. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 120 days after the last dose of study treatment.
Prior/Concomitant Therapy
18. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (ie, CTLA-4, OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
19. Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (ie, must be ≤Grade 1 or at baseline) from AEs due to previously administered agents.
Note: Upon consultation with the Sponsor, denosumab may be allowed for bone protective purposes if dosing has been stable for ≥2 weeks before screening.
Note: Participants with ≤Grade 2 neuropathy are an exception and may qualify for the trial.
20. Has received a live vaccine within 30 days prior to the first dose of study treatment.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Prior/Concurrent Clinical Study Experience

21. Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks or 5 half-lives after the last dose of the previous investigational agent.

 

Trattamento sperimentale: 

Pembrolizumab

Trattamento di controllo: 

Placebo

Obiettivi primari dello studio: 

- Objective: To compare DFS as assessed by the investigator for participants treated with pembrolizumab versus those receiving placebo

Obiettivi secondari dello studio: 

- Objective: To compare OS for participants treated with pembrolizumab versus those receiving placebo
- To compare the safety and tolerability profiles for participants treated with pembrolizumab versus those receiving placebo
- To compare measures of disease recurrencespecific survival (DRSS), as assessed by the investigator, in participants treated with pembrolizumab versus those receiving placebo
- To compare DFS and OS according to participants’ PD-L1 expression status (Positive, Negative) for participants treated
with pembrolizumab versus those receiving placebo
- To evaluate pharmacokinetic (PK) parameters and the presence of antidrug antibodies (ADA)
- To evaluate patient-reported outcomes (PROs) with the European Organization for the Research and Treatment of Cancer
Quality of Life Questionnaire C30 (EORTCQLQ-C30) and the Functional Assessment of Cancer Therapy Kidney Symptom Index
Disease Related Symptoms (FKSI-DRS)
- To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may be indicative of clinical response/resistance,
safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab
- To evaluate PROs with the EORTC-QLQC30 and FKSI-DRS and to characterize utilities with the EuroQol 5 Dimensions 5
Levels (EQ-5D-5L)

 

Centri partecipanti

Nord Italia

IRCCS - IRST
Via P. Maroncelli 40 - 47014 Meldola - FC

Riferimento: Dr. Ugo De Giorgi

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

Riferimento: Dr. Giuseppe Procopio
Telefono: 0223904450
Email: giuseppe.procopio@istitutotumori.mi.it

 

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

Riferimento: Dr. Franco Nolè
Telefono: 0257489460
Email: franco.nole@ieo.it

 

A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO

Riferimento: Dr. Roberto Sabbatini

 

A.O.U San Luigi Gonzaga
Regione Gonzole 10 - 10043 Orbassano - TO

Riferimento: Dr. Marcello Tucci

 

Centro Italia

Istituto Toscano Tumori Ospedale San Donato
Via Pietro Nenni 20 - 52100 Arezzo - AR

Riferimento: Dr.ssa Alketa Hamzaj
Telefono: 0575255439

 

Istituto Nazionale Tumori “Regina Elena”
Via Elio Chianesi 53 - 00144 Roma - RM

Riferimento: Dr. Ferretti
Telefono: 0652666919

 

Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA

Riferimento: Dr. Gaetano Facchini
Telefono: 0815903637

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2016-004351-75

Data di inserimento: 16.02.2018

Data di aggiornamento: 29.11.2018

Promotore

Merck Sharp & Dohme Corp.

CRO

/

Principal Investigator ITALIA

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Riferimento: Dr. Giuseppe Procopio

Telefono: 0223904450

Email: giuseppe.procopio@istitutotumori.mi.it

Localita: Milano

 

<< Torna a "Tutti gli studi"