Triple-Negative Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
ERYTECH Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible for the study if all the following criteria are met: 1. Female or male, 18 years of age or older. 2. Histologically confirmed diagnosis of invasive breast cancer. 3. Metastatic or locally recurrent inoperable breast cancer not previously treated with chemotherapy. 4. Diagnosis of triple negative breast cancer, defined as the absence of expression of the following receptors in the primary and/or metastatic tumor tissue: - HER2 protein over-expression and/or gene amplification, defined as: a) fluorescent in situ hybridization (FISH)-negative: FISH ratio 12 weeks according to the Investigator’s clinical judgment. 9. Females of childbearing potential must have a negative pregnancy test at screening and an additional pregnancy test prior to first dose. Females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 6 months after the last dose of study treatment. 10. Adequate laboratory parameters at baseline (obtained 60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the institutional normal range. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockcroft-Gault formula). For patients with a Body Mass Index (BMI) >30 Kg/m2, lean body weight should be used instead. - Acceptable coagulation parameters: plasma antithrombin III >70%, fibrinogen =1.5 g/dL, international normalized ratio (INR) =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: A patient is not eligible to participate in the study if any of the following criteria are met: 1. Pregnant or lactating females. 2. Original primary tumor or subsequent relapse known to be positive for ER, PgR, or HER2 receptors, as defined above. 3. Confirmed BRCA1 or BRCA2 mutation carrier. 4. Prior systemic therapy for metastatic or locally recurrent breast cancer. 5. Bone as the only site of disease. 6. Presence of untreated symptomatic central nervous system (CNS) metastases as determined by MRI or CT scan performed during screening. 7. Prior radiotherapy to the only area of measurable disease. 8. Prophylactic use of supportive bone-modifying therapy for skeletal-related events (e.g., bisphosphonate, pamidronate, or denosumab), unless treatment is initiated prior to or within 7 days after randomization. 9. History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization. 10. Neurosensory neuropathy >Grade 2 at baseline. 11. Known history of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C. 12. Known hypersensitivity to gemcitabine, platinum compounds, mannitol, or asparaginase. 13. Treatment with warfarin. Warfarin must be replaced with low-molecular weight heparin. 14. History of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >5 years. 15. Any other severe acute or chronic condition that may increase the risk of study participation, including: - Current or history within 6 months prior to randomization of medically significant cardiovascular disease including symptomatic congestive heart failure >New York Heart Association (NYHA) Class II, unstable angina pectoris, clinically significant cardiac arrhythmia. - Psychiatric illness/social situations or any other serious uncontrolled medical disorders that in the opinion of the Investigator would limit compliance with study requirements. 16. Receiving therapy in a concurrent clinical study. Patients must agree not to participate in any other interventional clinical studies during their participation in this trial while on study treatment. Patients taking part in surveys or observational studies are eligible to participate in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether the addition of eryaspase to gemcitabine and carboplatin improves the objective response rate (ORR) by modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by an independent radiological review (IRR) in firstline treatment of locally recurrent or metastatic triple-negative breast cancer (TNBC) compared with chemotherapy alone.;Secondary Objective: The secondary objectives of this study are: To compare the ORR between the two treatment arms as determined by the Investigator’s assessment; To compare the CBR between the two treatment arms; To compare the DoR between the two treatment arms; To compare progression-free survival (PFS) between the two treatment arms; To compare OS between the two treatment arms; To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone; To evaluate the change in F-18 fluorodeoxyglucose (FDG) tumor uptake as a predictor of clinical response following one cycle of treatment with eryaspase and chemotherapy; To determine the PK and pharmacodynamics of eryaspase; To assess the immunogenicity of eryaspase as determined by the induction of antiasparaginase antibodies and neutralizing antibodies; To evaluate the relationship of clinical outcome with relevant biomarkers and tumorspecific mutational changes present in tumor tissues and blood samples;Primary end point(s): The primary endpoint is ORR in evaluable patients, assessed by independent radiological review.;Timepoint(s) of evaluation of this end point: The final analysis will be based on Fisher’s combination test in light of the adaptive nature of the design for Part 1 and the sample size re-estimation. The onesided p-value for the Part 1 data prior to the sample size review (p1) will be combined with the p-value for the Part 1 data following the sample size review (p2) to give a one-sided p-value for the full Part 1 data. Statistical significance at the one-side | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate PFS, measured as the interval from randomization until objective tumor progression or death from any cause, whichever occurs first. To evaluate BOR recorded from start of treatment until the EoT and will be determined based on evaluations of target, non-target, and new lesions. Clinical benefit rate (CBR) is defined as the proportion of patients with best response, according to modified RECIST 1.1, of CR, PR, or SD for at least 16 weeks. Evaluation of Duration of Treatment, defined as time from randomization to discontinuation of study treatment for any reason. To evaluate the Duration of Response measured from the time measurement criterias are first met for CR/PR (whichever is first recorded) per modified RECIST 1.1 until the first date that recurrent disease or PD is objectively documented. Overall survival is defined as the interval from the date of randomization to the date of death from any cause.;Timepoint(s) of evaluation of this end point: To be measured from the date of randomization to the date of death from any cause compared between two treatment arms. Patients who are not known to have died will be censored at the date of last contact, and this will apply as of the date of data cut-off for any particular analysis. | — |
Countries
Belgium, France, Hungary, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactIman El-Hariry
ERYTECH Pharma
Outcome results
None listed