Clinical Trials /

Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 1st Line Treatment of TNBC (TRYbeCA-2)

NCT03674242

Description:

This is an open-label, multicenter, randomized, Phase 2/3 study in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for locally recurrent or metastatic disease.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 1st Line Treatment of TNBC (TRYbeCA-2)
  • Official Title: A Randomized Phase 2/3 Study of Eryaspase in Combination With Gemcitabine and Carboplatin Chemotherapy Versus Chemotherapy Alone as First-line Treatment in Patients With Metastatic or Locally Recurrent Triple-negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: GRASPA-TNBC-2018-02
  • NCT ID: NCT03674242

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
eryaspase (L-asparaginase encapsulated in red blood cells)ERY001, GRASPAEryaspase plus Chemotherapy
GemcitabineGemzarChemotherapy alone
CarboplatinParaplatinChemotherapy alone

Purpose

This is an open-label, multicenter, randomized, Phase 2/3 study in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for locally recurrent or metastatic disease.

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 who have
           not received prior systemic therapy for locally recurrent or metastatic disease. Data
           analysis of Part 1 will inform choices for the final design and patient population in
           Part 2 (Phase 3 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.

      Part 1 is the focus of the current trial.

      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 (G/C), 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.
    

Trial Arms

NameTypeDescriptionInterventions
Eryaspase plus ChemotherapyExperimentaleryaspase 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.
  • eryaspase (L-asparaginase encapsulated in red blood cells)
  • Gemcitabine
  • Carboplatin
Chemotherapy aloneActive ComparatorGemcitabine plus carboplatin dosed at Day 1 and Day 8 of each 3-week cycle
  • Gemcitabine
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          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:

               -  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. 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

          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

         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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:1 year after last patient randomized
Safety Issue:
Description:To determine whether the addition of eryaspase to chemotherapy improves the ORR by modified RECIST 1.1 as determined by an independent radiological review

Secondary Outcome Measures

Measure:Clinical Benefit Rate (CBR)
Time Frame:1 year after last patient randomized
Safety Issue:
Description:To compare the clinical benefit rate (CBR) between the two treatment arms
Measure:Duration of Response (DoR)
Time Frame:1 year after last patient randomized
Safety Issue:
Description:To compare the duration of response (DoR) between the two treatment arms
Measure:Progression-Free Survival (PFS)
Time Frame:1 year after last patient randomized
Safety Issue:
Description:To compare progression-free survival (PFS) between the two treatment arms.
Measure:Overall Survival (OS)
Time Frame:1 year after last patient randomized
Safety Issue:
Description:To compare overall survival (OS) between the two treatment arms.
Measure: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
Safety Issue:
Description: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

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ERYtech Pharma

Last Updated

January 16, 2020