BRCA-related metastatic breast cancer MedDRA version: 20.0 Level: LLT Classification code 10006178 Term: Breast adenocarcinoma stage IV System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: [MK-3475]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: -
Other descriptive nam
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA DI MODENA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be willing and able to provide written informed consent/assent for the trial. 2. Be ¿ 18 years of age on day of signing informed consent. 3. Patients must have metastatic confirmed breast cancer 4. Disease progression by radiological techniques within 12 months prior to signing informed consent 5. Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (unknown significance variants) 6. Have measurable disease based on RECIST 1.1. 7. Prior chemotherapy with anthracyclines and taxanes has to be administered in neoadjuvant or adjuvant setting. 8. 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 9. Have a performance status of 0 or 1 on the ECOG Performance Scale. 10. Life expectancy of greater than 3 months 11. Demonstrate adequate organ function as defined. All screening labs should be performed within 10 days of treatment initiation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. 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. 2. Has a benign variant of BRCA1/2 genes 3. 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. 4. Has a known history of active TB (Bacillus Tuberculosis) 5. Hypersensitivity to pembrolizumab or any of its excipients. 6. 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. 7. 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. 8. 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. 9. 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. 10. 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. 11. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 12. Has an active infection requiring systemic therapy. 13. 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. 14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 15. 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. 16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 17. Has a known history of Human Immunodeficiency Virus
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective response rate (ORR);Secondary Objective: - The time to progression (TTP) - The duration of response (DOR) - The Disease Control Rate (DCR) - The overall survival (OS) - Assessment biological parameters of PD-1+TILs - ;Primary end point(s): The objective response rate (ORR) (complete response plus partial response) will be evaluated according to RECIST criteria;Timepoint(s) of evaluation of this end point: every cycle in phase COMBO / every 4 cycle in phase MONO | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The time to progression (TTP) will be calculated as the interval between the enrolment and the occurrence of local tumor progression (including ipsilateral and contra-lateral breast) or distant tumor progression; The duration of response (DOR) will be measured from the time of the first ORR is recorded to the date of progression is objectively documented.; The Disease Control Rate (DCR) will be evaluated as the percentage of patients with ORR and stable disease; The overall survival (OS) will be calculated as the interval between the enrolment and the death from any cause or the last date the patient was known to be alive; The biological parameters of PD-1+TILs will be evaluated by immunohistochemistry on primary surgical specimen, and, when evaluable, on metastatic biopsy.;Timepoint(s) of evaluation of this end point: every cycle in phase COMBO / every 4 cycle in phase MONO; every cycle in phase COMBO / every 4 cycle in phase MONO; every cycle in phase COMBO / every 4 cycle in phase MONO; interval between the enrolment and the death; screening | — |
Countries
Italy
Contacts
Public ContactClinical Trials Quality Team
Azienda Ospedaliero-Universitaria di Modena
Outcome results
None listed