Study to determine whether the addition of eryaspase to gemcitabine and carboplatin will reduce the tumor burden and stabilizate the tumor progression.

Phase 1

• Conditions: Triple-Negative Breast Cancer; MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002211-10-ES
• Lead Sponsor: ERYTECH Pharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-09-17
• Last Update Posted: 9 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

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 <2.2), or
b) immunohistochemistry (IHC) 0-1+, or c) IHC 2+/3+ AND FISH-negative (FISH ratio <2.2) (1).
- Estrogen receptor (ER), defined as <1% staining by IHC (2).
- AND progesterone receptors (PgR), defined as <1% staining by IHC.
5. Measurable lesion(s) per RECIST 1.1.
6. Available archival or fresh tumor tissue. Formalin-fixed paraffin-embedded (FFPE) block is preferred, or a minimum of 10 unstained, consecutive FFPE slides of one archived block is required.
7. Adequate performance status (PS) score (see Appendix 11.2):
o Eastern Cooperative Oncology Group (ECOG) PS score of 0, or
o ECOG PS score 1 and score =80 on Karnofsky Performance Status (KPS) scale.
8. Life expectancy of >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 <14 days prior to randomization):
- Absolute neutrophil count =1.5 x 109/L.
- Hemoglobin =9 g/dL.
- Platelet count =100,000/mm3 (100 x 109/L).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
=2.5 x upper limit of normal (ULN) (=5 x ULN in presence of liver metastases).
- Total bilirubin = 1.5 x institutional ULN.
- Serum creatinine within normal limits or calculated clearance >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) <1.5, and partial thromboplastin time (PTT) = institutional ULN.
- Serum albumin =3.0 g/dL.
11. Patients must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provided written informed consent.
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 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified