Advanced HER-2 negative breast cancer MedDRA version: 18.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Sponsors
Fundación CRIS de investigación para vencer el cáncer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. 2. Age > 18 years at time of study entry. 3. Confirmed diagnosis of advanced/metastatic HER-2 negative breast cancer. 4. Patients previously treated with any regimen containing chemotherapy plus bevacizumab as first line of treatment, switched to maintenance treatment with bevacizumab alone and disease progression during this treatment. At least 6 weeks (two doses) must have passed since the last chemotherapy administration, while in treatment with bevacizumab alone, in order to consider bevacizumab monotherapy as maintenance therapy. Any disease progression according to RECIST 1.1 criteria after this timeframe will be considered ?progression during bevacizumab maintenance?. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life expectancy of > 24 weeks. 7. Adequate normal organ and marrow function as defined below: - Haemoglobin ? 9.0 g/dL. - Absolute neutrophil count (ANC) ? 1.5 x 109/L (> 1500 per mm3). - Platelet count ? 100 x 109/L (>100,000 per mm3). - Serum bilirubin ? 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert?s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. - AST (SGOT)/ALT (SGPT) ? 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ? 5x ULN. - Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: - Males: Creatinine CL (mL/min) = Weight (kg) x (140 ? Age) / 72 x serum creatinine (mg/dL) - Females: Creatinine CL (mL/min) = (Weight (kg) x (140 ? Age)/72 x serum creatinine (mg/dL)) x 0.85 8. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ?60 years old and no menses for ?1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. 9. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study or in any support activity. Previous enrolment in the present study. 2. Participation in another clinical study with an investigational product during the last 4 weeks. 3. Any previous treatment with a CTLA-4 inhibitor, PD-1 or PD-L1 inhibitor, including DURVALUMAB. 4. History of another primary malignancy except for: -Malignancy treated with curative intent and with no known active disease ?5 years before the first dose of study drug and of low potential risk for recurrence. - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. - Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ. 5. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) other than bevacizumab 28 days prior to the first dose of study drug: 28 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.) 6. Mean QT interval corrected for heart rate (QTc) ?470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia?s Correction. 7. Current or prior use of immunosuppressive medication within 28 days before the first dose of DURVALUMAB, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. 8. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy, including proteinuria related to bevacizumab. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy). 9. Any prior Grade ?3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved AE >Grade 1. 10. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave?s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 11. Active or prior documented inflammatory bowel disease (e.g., Crohn?s disease, ulcerative colitis). 12. History of primary immunodeficiency. 13. History of allogeneic organ transplant. 14. History of hypersensitivity to DURVALUMAB or any excipient. 15. History of hypersensitivity to the combination agent bevacizumab 16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. 17. Anticoagulation therapy (except low-dose heparin and/or wash out with heparin as needed to maintain a permanent intravenous device) or antiplatelet therapy (except for treatm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the immunodynamics in peripheral blood and in the tumor of combined administration of DURVALUMAB and the monoclonal antibody bevacizumab in advanced HER-2- negative breast cancer patients that have progressed to bevacizumab-based treatment.;Secondary Objective: - To study the relationship between T-cell exhaustion parameters and failure of monoclonal-antibody-based treatment. - To study if the reversion of the phenomenon of T-cell exhaustion by DURVALUMAB induces therapeutic benefit (measured by clinical benefit (CR+PR+SD) at 4 months after inclusion of DURVALUMAB in patients that have progressed to bevacizumab alone) - To evaluate safety of combination of both DURVALUMAB and bevacizumab.;Primary end point(s): Decrease in the percentage of TRegs;Timepoint(s) of evaluation of this end point: - every 4 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - disease control rate - duration of response - progression-free survival - safety profile;Timepoint(s) of evaluation of this end point: - every 8 weeks - every 8 weeks - every 8 weeks - every 2 weeks | — |
Countries
Spain
Contacts
Public ContactClinical Operations Department
APICES SOLUCIONES, S.L.
Outcome results
None listed