Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone for the Treatment of TNBC (TRYbeCA-2)
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|ClinicalTrials.gov Identifier: NCT03674242|
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : September 28, 2021
|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|
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)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||64 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
Experimental: Eryaspase plus Chemotherapy
eryaspase 100 U/kg dosed at Day 1 and Day 8 of each 3-week cycle in combination with
Drug: eryaspase (L-asparaginase encapsulated in red blood cells)
IV infusion 100 U/kg
Other Name: ERY001, GRASPA
IV infusion 1000 mg/m2
Other Name: Gemzar
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
IV infusion 1000 mg/m2
Other Name: Gemzar
IV infusion AUC2
Other Name: Paraplatin
- 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.
- 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.
- 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).
- Progression-Free Survival (PFS) [ Time Frame: 1 year after last patient randomized. ]To compare progression-free survival (PFS) between the two treatment arms.
- Duration of Response (DoR) [ Time Frame: 1 year after last patient randomized. ]To compare the duration of response (DoR) between the two treatment arms.
- Overall Survival (OS) [ Time Frame: 1 year after last patient randomized. ]To compare overall survival (OS) between the two treatment arms.
- 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.
- 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.
- 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.
- 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.
- 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)
- 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)
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
|Contact: Iman El-Hariry, MD, PhD||+33 478 788 email@example.com|
|Contact: Jean-Baptiste Bertrand, PhD||+33 478 781 firstname.lastname@example.org|
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