Triple Negative Breast CancerPhase 2/3NCT03674242
Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone for the Treatment of TNBC (TRYbeCA-2)
A Phase 2/3 study testing eryaspase (L-asparaginase encapsulated in red blood cells), Gemcitabine and Carboplatin in people with Triple Negative Breast Cancer, run by ERYtech Pharma at 16 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- eryaspase (L-asparaginase encapsulated in red blood cells), Gemcitabine and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 16 sitesin 3 countries
- Study dates
- 13 Jun 2019to 31 Mar 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male, 18 years of age or older.
- Histologically or cytologically confirmed diagnosis of invasive breast cancer.
- Metastatic or locally recurrent inoperable breast cancer with no more than one prior systemic therapy.
- 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).
Show all 14Show fewer
- AND progesterone receptors (PgR), defined as <1% staining by IHC.
- Measurable lesion(s) per RECIST 1.1.
- Available archival or fresh tumor tissue.
- Adequate performance status (PS) score.
- Life expectancy of >12 weeks according to the Investigator's clinical judgment.
- 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.
- Adequate laboratory parameters at baseline (obtained <14 days prior to randomization)
- 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.
Who cannot join
- Pregnant or lactating females.
- Known BRCA1 or BRCA2 mutation carrier.
- Bone as the only site of disease.
- Presence of untreated symptomatic central nervous system (CNS) metastases as determined by MRI or CT scan performed during screening.
- Prior radiotherapy to the only area of measurable disease.
- 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.
Show all 15Show fewer
- History of recent clinical pancreatitis, according to revised Atlanta criteria, within 3 months of randomization.
- Neurosensory neuropathy >Grade 2 at baseline.
- Known history of infection with human immunodeficiency virus (HIV) and/or active infection with hepatitis B or hepatitis C.
- Known hypersensitivity to gemcitabine, platinum compounds or asparaginase.
- Patients who have received live or live attenuated vaccines within 3 weeks of randomization.
- Pre-existing coagulopathy (e.g. hemophilia).
- 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.
- Any other severe acute or chronic condition/treatments that may increase the risk of study participation
- 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.
Trial locations and contacts
16 sites in 3 countries.
16 sites in 3 countries
Spain8 sites
Complejo Hospitalario Universitario A Coruña
A Coruña
Hospital Universitario Germans Trias i Pujol
Badalona
Hospital Universitario Arnau Vilanova
Lleida
Fundacion Jimenez Diaz
Madrid
Hospital Clinico San Carlos
Madrid
Hospital Universitario Quirón Madrid
Madrid
Hospital Universitario Ramon y Cajal
Madrid
Hospital Universitario Virgen del Rocio
Seville
Belgium5 sites
ZNA Middelheim
Antwerp
Institut Jules Bordet
Brussels
UZ Brussel
Brussels
Grand Hôpital de Charleroi asbl
Charleroi
Clinique Sainte-Elisabeth
Namur
Hungary3 sites
Debreceni Egyetem - Klinikai Kozpont - Onkologiai Klinika
Debrecen
Bacs Kiskun Megyei Korhaz
Kecskemét, 6000
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
Szolnok, 5000
About this study
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
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.
Read the 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)
- Conditions
- Triple Negative Breast Cancer
- Being tested
- eryaspase (L-asparaginase encapsulated in red blood cells), Gemcitabine, Carboplatin
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eryaspase (L-asparaginase encapsulated in red blood cells)Drug
Also called ERY001, GRASPA
IV infusion 100 U/kg
GemcitabineDrug
Also called Gemzar
IV infusion 1000 mg/m2
CarboplatinDrug
Also called Paraplatin
IV infusion AUC2
| Study group | Role | What they receive |
|---|---|---|
| Eryaspase plus Chemotherapy | Experimental | 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. Receives: Drug: eryaspase (L-asparaginase encapsulated in red blood cells); Drug: Gemcitabine; Drug: Carboplatin |
| Chemotherapy alone | Active comparator | Gemcitabine plus carboplatin dosed at Day 1 and Day 8 of each 3-week cycle Receives: Drug: Gemcitabine; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Control Rate (DCR)
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.
Measured: 1 year after last patient randomized
Secondary outcomes (11)
Disease Control Rate (DCR)
To compare the DCR between the two treatment arms as determined by the Investigator's assessment.
Measured: 1 year after last patient randomized
Objective response rate (ORR)
To compare the objective response rate (ORR) between the two treatment arms as determined by the independent radiological review (IRR).
Measured: 1 year after last patient randomized.
Progression-Free Survival (PFS)
To compare progression-free survival (PFS) between the two treatment arms.
Measured: 1 year after last patient randomized.
Duration of Response (DoR)
To compare the duration of response (DoR) between the two treatment arms.
Measured: 1 year after last patient randomized.
Overall Survival (OS)
To compare overall survival (OS) between the two treatment arms.
Measured: 1 year after last patient randomized.
Incidence of treatment emergent adverse events as assessed by CTCAE v5.0
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.
Measured: Collected from time of informed consent until 30 days after last study treatment.
Clinical response assessed by F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
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.
Measured: Collected at baseline and within 3 days of the end of Cycle 1 in all patients.
Eryaspase induced immunogenecity
To determine the anti-asparaginase antibodies titer.
Measured: Samples will be collected pre-dose at Cycle 1 Day 1 and pre-dose at Cycle 3 Day 1 (each Cycle is 21 days)
Biomarkers potentials in predicting eryaspase activity.
To determine DNA, RNA and protein levels present in tumor tissues and blood samples.
Measured: 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.
Pharmacokinetics of eryaspase
To determine total and plasma asparaginase activity (U/L)
Measured: 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)
Pharmacodynamics of eryaspase
To determine plasma concentrations of asparagine and glutamine (µmol/L)
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2018
- Study start13 Jun 2019
- Primary completion31 Mar 2022
- Study completion31 Mar 2022
Why it stopped: sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- ERYtech Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03674242
- Sponsor's protocol ID
- GRASPA-TNBC-2018-02
- Status last verified
- Jul 2022
- First submitted
- 14 Sep 2018
- Last updated
- 1 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03674242
- Acronym / sponsor ID
- GRASPA-TNBC-2018-02
- Conditions
- Triple Negative Breast Cancer
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor decision
- Enrolment
- 27 participants (actual)
- Lead sponsor
- ERYtech PharmaIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2019 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 31 Mar 2022 (actual)
- First posted
- 17 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eryaspase plus Chemotherapy | Experimental | Drug: eryaspase (L-asparaginase encapsulated in red blood cells), Drug: Gemcitabine, Drug: Carboplatineryaspase 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. |
| Chemotherapy alone | Active comparator | Drug: Gemcitabine, Drug: CarboplatinGemcitabine plus carboplatin dosed at Day 1 and Day 8 of each 3-week cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Female or male, 18 years of age or older.
- Histologically or cytologically confirmed diagnosis of invasive breast cancer.
- Metastatic or locally recurrent inoperable breast cancer with no more than one prior systemic therapy.
- 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:
- Measurable lesion(s) per RECIST 1.1.
Key exclusion criteria (15 listed)
- Pregnant or lactating females.
- Known BRCA1 or BRCA2 mutation carrier.
- Bone as the only site of disease.
- Presence of untreated symptomatic central nervous system (CNS) metastases as determined by MRI or CT scan performed during screening.
- Prior radiotherapy to the only area of measurable disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eryaspase (L-asparaginase encapsulated in red blood cells)Also: ERY001, GRASPAIV infusion 100 U/kg | Drug | Eryaspase plus Chemotherapy |
| GemcitabineAlso: GemzarIV infusion 1000 mg/m2 | Drug | Chemotherapy alone, Eryaspase plus Chemotherapy |
| CarboplatinAlso: ParaplatinIV infusion AUC2 | Drug | Chemotherapy alone, Eryaspase plus Chemotherapy |
Primary outcome
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.
11 secondary outcomes
Disease Control Rate (DCR)
Time frame: 1 year after last patient randomized
Objective response rate (ORR)
Time frame: 1 year after last patient randomized.
Progression-Free Survival (PFS)
Time frame: 1 year after last patient randomized.
Duration of Response (DoR)
Time frame: 1 year after last patient randomized.
Overall Survival (OS)
Time frame: 1 year after last patient randomized.
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.
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.
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)
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.
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)
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)
Results and safety
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2022.
Related trials for Triple Negative Breast Cancer
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruitingPhase 1/2
Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...
Colorectal Neoplasms, Breast Neoplasms
RecruitingPhase 2
Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)
Breast Neoplasms, Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
16 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing eryaspase (L-asparaginase encapsulated in red blood cells), Gemcitabine and Carboplatin in people with Triple Negative Breast Cancer, run by ERYtech Pharma at 16 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Spain, Belgium, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Control Rate (DCR) (time frame: 1 year after last patient randomized). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2022.