Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone for the Treatment of TNBC (TRYbeCA-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03674242
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : September 28, 2021
Sponsor:
Information provided by (Responsible Party):
ERYtech Pharma

Brief Summary:
This is an open-label, multicenter, randomized, Phase 2/3 study in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC) with no more than one prior systemic therapy for locally recurrent or metastatic disease.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Drug: eryaspase (L-asparaginase encapsulated in red blood cells) Drug: Gemcitabine Drug: Carboplatin Phase 2 Phase 3

Detailed Description:

The study will consist of 2 parts:

  • Part 1 is an open-label, multicenter, randomized Phase 2 exploratory study that will investigate the clinical activity of the combination of eryaspase and gemcitabine/carboplatin in patients with locally recurrent or metastatic TNBC. Data analysis of Part 1 will inform choices for the final design and patient population in Part 2 (Phase 3 study). Patients recruited into Part 1 will not be included in the Intent-to-Treat patient (ITT) population of Part 2 of the study.
  • Part 2 will be a randomized Phase 3 study designed to evaluate the efficacy of the combination of eryaspase and gemcitabine/carboplatin in TNBC patients. The current protocol will focus on Part 1.

Part 1 is the focus of the current protocol, with a primary endpoint of DCR. DCR data as determined by an IRR will determine whether or not proceeding to Part 2 is warranted. If so, Part 2 will be implemented via a major amendment to the protocol. Meanwhile, sites will remain open with the expectation that Part 2 will be activated

After providing informed consent and completing the screening assessments, patients who meet all inclusion and no exclusion criteria will be randomized in a 1:1 ratio to one of the following treatment arms:

  • Arm A (experimental arm): eryaspase 100 U/kg on Days 1 and 8 of combination chemotherapy with gemcitabine/carboplatin, or
  • Arm B (control arm): gemcitabine/carboplatin combination.

Treatment will continue until objective disease progression, unacceptable toxicity, or the patient's withdrawal of consent.

A survival follow-up period will include the collection of survival, progression of disease if applicable, subsequent anti-cancer therapy every 12 weeks (± 1 week)

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2/3 Study of Eryaspase in Combination With Gemcitabine and Carboplatin Chemotherapy Versus Chemotherapy Alone for the Treatment of Patients With Metastatic or Locally Recurrent Triple-Negative Breast Cancer
Actual Study Start Date : June 13, 2019
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Eryaspase plus Chemotherapy

eryaspase 100 U/kg dosed at Day 1 and Day 8 of each 3-week cycle in combination with

  • Gemcitabine IV infusion 1000 mg/m2, Day 1 and Day 8.
  • Carboplatin IV infusion at a calculated area under the curve (AUC) of 2.0 (AUC2), Day 1 and Day 8.
Drug: eryaspase (L-asparaginase encapsulated in red blood cells)
IV infusion 100 U/kg
Other Name: ERY001, GRASPA

Drug: Gemcitabine
IV infusion 1000 mg/m2
Other Name: Gemzar

Drug: Carboplatin
IV infusion AUC2
Other Name: Paraplatin

Active Comparator: Chemotherapy alone
Gemcitabine plus carboplatin dosed at Day 1 and Day 8 of each 3-week cycle
Drug: Gemcitabine
IV infusion 1000 mg/m2
Other Name: Gemzar

Drug: Carboplatin
IV infusion AUC2
Other Name: Paraplatin




Primary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: 1 year after last patient randomized ]
    To determine whether the addition of eryaspase to gemcitabine and carboplatin improves the disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by an independent radiological review (IRR) in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC) compared with chemotherapy alone.


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: 1 year after last patient randomized ]
    To compare the DCR between the two treatment arms as determined by the Investigator's assessment.

  2. Objective response rate (ORR) [ Time Frame: 1 year after last patient randomized. ]
    To compare the objective response rate (ORR) between the two treatment arms as determined by the independent radiological review (IRR).

  3. Progression-Free Survival (PFS) [ Time Frame: 1 year after last patient randomized. ]
    To compare progression-free survival (PFS) between the two treatment arms.

  4. Duration of Response (DoR) [ Time Frame: 1 year after last patient randomized. ]
    To compare the duration of response (DoR) between the two treatment arms.

  5. Overall Survival (OS) [ Time Frame: 1 year after last patient randomized. ]
    To compare overall survival (OS) between the two treatment arms.

  6. Incidence of treatment emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Collected from time of informed consent until 30 days after last study treatment. ]
    To evaluate the safety and tolerability of eryaspase in combination with chemotherapy versus chemotherapy alone by assessing the number of patients with treatment emergent adverse events per CTCAE v5.0.

  7. Clinical response assessed by F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging [ Time Frame: Collected at baseline and within 3 days of the end of Cycle 1 in all patients. ]
    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.

  8. Eryaspase induced immunogenecity [ Time Frame: Samples will be collected pre-dose at Cycle 1 Day 1 and pre-dose at Cycle 3 Day 1 (each Cycle is 21 days) ]
    To determine the anti-asparaginase antibodies titer.

  9. Biomarkers potentials in predicting eryaspase activity. [ Time Frame: Tissue samples will be collected at baseline. Blood samples for biomarker analysis will be collected during screening, at Cycle 1 Day 1 and Day 8, and at Day 1 of every second cycle ( each is 21 days) until End of Treatment (EOT) visit. ]
    To determine DNA, RNA and protein levels present in tumor tissues and blood samples.

  10. Pharmacokinetics of eryaspase [ Time Frame: Samples will be collected the first day (D1) and the eight day (D8) of Cycle 1 and Cycle 3 treatment (each Cycle is 21 days) and at End of treatment (EOT) ]
    To determine total and plasma asparaginase activity (U/L)

  11. Pharmacodynamics of eryaspase [ Time Frame: Samples will be collected the first day (D1) and the eight day (D8) of Cycle 1 and Cycle 3 treatment (each Cycle is 21 days) and at End of treatment (EOT) ]
    To determine plasma concentrations of asparagine and glutamine (µmol/L)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 tumor 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
    • 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.
  7. Adequate performance status (PS) score.
  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)
  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.

Exclusion Criteria:

  1. Pregnant or lactating females.
  2. Known BRCA1 or BRCA2 mutation carrier.
  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 non-melanoma 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
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03674242


Contacts
Layout table for location contacts
Contact: Iman El-Hariry, MD, PhD +33 478 788 168 iman.elhariry@erytech.com
Contact: Jean-Baptiste Bertrand, PhD +33 478 781 586 jb.bertrand@erytech.com

Locations
Layout table for location information
Belgium
ZNA Middelheim Recruiting
Antwerpen, Belgium
Contact: Wesley Teurfs         
Institut Jules Bordet Recruiting
Brussels, Belgium
Contact: Ahmad Awada         
UZ Brussel Recruiting
Brussels, Belgium
Contact: Christel Fontaine         
Grand Hôpital de Charleroi asbl Recruiting
Charleroi, Belgium
Contact: Jean-Luc Canon         
Clinique Sainte-Elisabeth Recruiting
Namur, Belgium
Contact: Stephanie Henry         
Hungary
Debreceni Egyetem - Klinikai Kozpont - Onkologiai Klinika Recruiting
Debrecen, Hungary
Contact: Peter Arkosky         
Bacs Kiskun Megyei Korhaz Recruiting
Kecskemét, Hungary, 6000
Contact: Zsolt Horvath, MD    +36304913443      
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet Recruiting
Szolnok, Hungary, 5000
Contact: Tibor Csoszi         
Spain
Hospital Universitario Germans Trias i Pujol Recruiting
Badalona, Spain
Contact: Vanesa Quiroga         
Complejo Hospitalario Universitario A Coruña Recruiting
La Coruña, Spain
Contact: Silvia Antolin         
Hospital Universitario Arnau Vilanova Recruiting
Lleida, Spain
Contact: Serafin Morales         
Fundacion Jimenez Diaz Recruiting
Madrid, Spain
Contact: Yann Izarzugaza         
Hospital Clinico San Carlos Recruiting
Madrid, Spain
Contact: Jose A Garcia Saenz         
Hospital Universitario Quirón Madrid Recruiting
Madrid, Spain
Contact: Miguel Angel Quintela         
Hospital Universitario Ramon y Cajal Recruiting
Madrid, Spain
Contact: Javier Cortes         
Hospital Universitario Virgen del Rocio Recruiting
Sevilla, Spain
Contact: Francisco J Salvador Bofill         
Sponsors and Collaborators
ERYtech Pharma
Layout table for additonal information
Responsible Party: ERYtech Pharma
ClinicalTrials.gov Identifier: NCT03674242    
Other Study ID Numbers: GRASPA-TNBC-2018-02
First Posted: September 17, 2018    Key Record Dates
Last Update Posted: September 28, 2021
Last Verified: September 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Asparaginase
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs