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-GB
• Lead Sponsor: ERYTECH Pharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-29
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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 or cytologically confirmed diagnosis of invasive breast cancer.
3. Metastatic or locally recurrent inoperable breast cancer with no more than one prior systemic therapy.
4. Diagnosis (original primary tumour or subsequent relapse) 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 negative 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. These include, but not limited to: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- intravaginal
- transdermal; progestogen-only hormonal contraception associated with inhibition of ovulation: - injectable, - implantable intrauterine device (IUD)
- bilateral tubal occlusion - vasectomy - condoms - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). The true abstinence is when this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception]
NOTE: A woman is considered of childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
NOTE: Since an indirect interaction between components of the oral contraceptives and free ASNase cannot be ruled out (potential increase in the risk of a change in coagulation parameters and thrombosis), oral contraceptives are not considered acceptable as contraceptive methods in the current clinical trial. A method other than oral contraception should be used in women of childbearing potential.
10. Adequate laboratory parameters at baseline (obtained <14 days prior to randomization)Laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the medical monitor.:
- Absolute neutrophil count =1.5

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. Known BRCA1 or BRCA2 mutation carrier. NOTE: Patients with unknown BRCA1/2 mutation status may be included in the study, but are required to be tested during the study
3. Bone as the only site of disease.
4. Presence of untreated symptomatic central nervous system (CNS) metastases as determined by MRI or CT scan performed during screening.
5. Prior radiotherapy to the only area of measurable disease.
6. 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.
7. History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.
8. Neurosensory neuropathy >Grade 2 at baseline.
9. Known history of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.
10. Known hypersensitivity to gemcitabine, platinum compounds, or asparaginase.
11. Patients who have received live or live attenuated vaccines within 3 weeks of randomization.
12. Pre-existing coagulopathy (e.g. hemophilia).
13. History of other malignancies except: adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >2 years.
14. Any other severe acute or chronic condition/treatments 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.
15. 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