Patologia: Neoplasie della mammella
Fase di studio: II
Richiesta mandatoria di tessuto: Sì
Linee di trattamento: Prima linea
Criteri di inclusione:
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Patients must have metastatic confirmed breast cancer
- Disease progression by radiological techniques within 12 months prior to signing informed consent
- Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (unknown significance variants)
- Have measurable disease based on RECIST 1.1.
- Prior chemotherapy with anthracyclines and taxanes has to be administered in neoadjuvant or adjuvant setting.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Life expectancy of greater than 3 months
- Demonstrate adequate organ function. All screening labs should be performed within 10 days of treatment initiation.
- 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.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.111.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 5.11.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Criteri di esclusione:
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a benign variant of BRCA1/2 genes
- 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.
- Has a known history of active Bacillus Tuberculosis
- Hypersensitivity to pembrolizumab or any of its excipients.
- 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.
- 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.
Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- 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.
- 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 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- 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.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has an active infection requiring systemic therapy.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father 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.
- Has received prior therapy with an anti-PD-1 (anti-programmed cell Death-1), anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV (Hepatitis C Virus) RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
Schema di trattamento:
Carboplatin at area under the time-concentration curve 6 (AUC 6) intravenously once every 3 weeks in combination with Pembrolizumab 200 mg intravenously every 3 weeks will be delivered for six courses. After that Pembrolizumab treatment will continue at the same schedule until occurrence of unacceptable toxicities or disease progression will arise.
Pembrolizumab Plus Carboplatin
Trattamento di controllo:
Obiettivi primari dello studio:
The primary endpoint will be Objective Responses Rate (ORR) (complete answers + partial answers) evaluated according to the RECIST criteria.
Ospedale Papa Giovanni XXIII Bergamo
Piazza OMS 1 - 24127 Bergamo - BG
IRCCS - IRST
Via P. Maroncelli 40 - 47014 Meldola - FC
Riferimento: Dr. Ugo De Giorgi
A.O.U. Policlinico di Modena
Via del Pozzo 71 - 41100 Modena - MO
Riferimento: Dr.ssa Laura Cortesi
Istituto Oncologico Veneto IRCCS
Via Gattamelata 64 - 35128 Padova - PD
Azienda Ospedaliero-Universitaria di Parma
Via Gramsci 14 - 43126 Parma - PR
AUSL/IRCCS di Reggio Emilia
Viale Risorgimento 80 - 42123 Reggio nell'Emilia - RE
Riferimento: Dr. Giancarlo Bisagni
Ospedale “Infermi” Rimini
Via Settembrini 2 - 47923 Rimini - RN
AOUI Verona - Borgo Trento
Piazzale Aristide Stefani 1 - 37126 Verona - VR
AOU Pisana - Santa Chiara
Via Roma 67 - 56126 Pisa - PI
Presidio Ospedaliero Vito Fazzi Asl Lecce
Piazzetta F. Muratore - 73100 Lecce - LE
AOU Policlinico Paolo Giaccone
Via del Vespro 129 - 90127 Palermo - PA
Numero di iscrizione a registro: 2016-001314-25
Data di inserimento: 24.11.2020
Azienda Ospedaliero-Universitaria Policlinico di Modena
Riferimento: Dr.ssa Laura Cortesi
Azienda Ospedaliero-Universitaria di Modena
Riferimento: Dr.ssa Laura Cortesi