Breast CancerPhase 1/2B-IMMUNENCT03356860
Safety and Efficacy of Durvalumab Combined to Neoadjuvant Chemotherapy in Localized Luminal B HER2(-) and Triple Negative Breast Cancer.
A Phase 1/2 study testing Paclitaxel, Epirubicin and Cyclophosphamide in people with Breast Cancer and Triple Negative Breast Cancer, run by Grand Hôpital de Charleroi at 4 sites in Belgium.
Trial summary
The study has a phase Ib and a phase II part. The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination with a dose- dense EC regimen in a neoadjuvant setting for early breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Triple Negative Breast Cancer, Luminal B
- What is being tested?
- Paclitaxel, Epirubicin and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 4 sitesBelgium
- Study dates
- 13 Apr 2017to 31 Dec 2023
- Phase
- Phase 1/2
- 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
- Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Female and male aged > 18 years at time of study entry.
- Patient has T1-T4 any N, M0, operable breast cancer
- Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma
- TNBC defined as negative oestrogen and progesterone receptors as per local laboratory testing and negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing
- Luminal B HER2 negative BC defined as positive oestrogen and/or progesterone receptors, a negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing and a Ki67 > 14%.
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- World Health Organisation (WHO) performance status of 0 or 1
- Adequate normal organ and marrow function as defined below:
- Haemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
- Platelet count ≥ 100 x 109/L (>100,000 per mm3)
- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit
- Serum creatinine CL>40 mL/min
- Normal cardiac function must be confirmed by ECG and cardiac function assessed by US imagery, radionucleotide ventriculography or MUGA, 4 weeks prior to randomization. Results must be above the normal limit of the institution
- Women must either be postmenopausal or must have a negative serum pregnancy test 14 days upon study entry.
- For a woman of childbearing potential, an effective method of birth control must be employed.
- Men must use 2 effective contraceptive measures or male sterilization with female partners of childbearing potential or pregnant female partners, or they must remain abstinent during the treatment period and for at least 6 months after the last dose of the study treatment.
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Subject accepts planned biological samples collection and their use for the trial propose.
Who cannot join
- Involvement in the planning and/or conduct of the study
- Previous enrolment in the present study
- Participation in another clinical study with an investigational product during the last 4 weeks
- Patient has locally recurrent or metastatic invasive BC
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug
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- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ or BC in situ.
- Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease
- Whatever the indication, receipt of a last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
- Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1
- Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from electrocardiograms (ECGs) using Fridericia's Correction
- Known or suspected congestive heart failure (>NYHA I) and / or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >140 / 90 mm Hg under treatment with two antihypertensive drugs), rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
- Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to durvalumab or any excipient
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Subjects with uncontrolled seizures.
- Known history of active tuberculosis
- Anticipation that a live attenuated vaccine will be required during the period from 30 days prior to the first planned durvalumab administration (e.i. week 18 and week 14 after study entry for the phase Ib and phase II respectively) to 5 months of durvalumab discontinuation. Influenza vaccination (inactivated forms only but not live attenuated forms) should be given during influenza season only (approximately October to March).
- Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control
- Men with female partners of childbearing potential or pregnant female partners who are not employing an effective method of birth control
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
Trial locations and contacts
4 sites in 1 country.
Belgium4 sites
Cliniques universitaires St Luc
Brussels, 1320
Grand Hôpital de Charleroi
Charleroi, Hainaut, 6000
CHU UCL Namur - Sainte-Elisabeth
Namur, Wallonia, 5000
CHU UCL Namur - Site Godinne
Yvoir, Wallonia, 5530
About this study
Official title: A Phase IB/II Study of Durvalumab (MEDI4736) Combined With Dose-dense EC in a Neoadjuvant Setting for Patients With Locally Advanced Luminal B HER2(-) or Triple Negative Breast Cancers.
The study has a phase Ib and a phase II part.
- The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination with a dose- dense EC regimen in a neoadjuvant setting for early breast cancer.
- The phase II aims to explore the efficacy of durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer.
- Conditions
- Breast Cancer, Triple Negative Breast Cancer, Luminal B
- Being tested
- Paclitaxel, Epirubicin, Cyclophosphamide, Durvalumab
- Keywords
- breast cancer, immunotherapy, anti-PD-L1
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol
80mg/m2 IV weekly from week 1 to week12
EpirubicinDrug
Also called Farmorubicine
90 mg/m2 IV Q 2 weeks from week 14 to week 20
CyclophosphamideDrug
Also called Endoxan
600 mg/m2 IV Q 2 weeks from week 14 to week 20
DurvalumabDrug
Also called MEDI4736
Durvalumab 1500 mg IV at week 14 and 18
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab | Experimental | Patients will received paclitaxel 80 mg/m2 IV weekly from week 1 to 12 and then an association of epirubicin 90 mg/m2 IV and cyclophosphamide 600 mg/m2 IV Q 2 weeks from week 14 to 20.
Durvalumab will be administered at 1500 mg IV at week 14 and week 18. Receives: Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Durvalumab |
| Standard | Active comparator | Patients will received paclitaxel 80 mg/m2 IV weekly from week 1 to 12 and then an association of epirubicin 90 mg/m2 IV and cyclophosphamide 600 mg/m2 IV Q 2 weeks from week 14 to 20. Receives: Drug: Paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
(serious) adverse event will be recorded
Measured: 74 weeks
Pathological response
Rate of complete pathological responses will be evaluated as a surrogate endpoint to evaluate efficacy
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2017
- Study start13 Apr 2017
- Primary completion21 Nov 2022
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grand Hôpital de Charleroi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Carrasco, MD, PhD, Principal investigator, GHdCJean-Luc Canon, MD, Principal investigator, GHdCFrançois Duhoux, MD, PhD, Principal investigator, Cliniques universitaires Saint-Luc (UCL)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03356860
- Sponsor's protocol ID
- ONCOGHdC2015_01
- Acronym
- B-IMMUNE
- Status last verified
- Nov 2024
- First submitted
- 23 Nov 2017
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB/II Study of Durvalumab (MEDI4736) Combined With Dose-dense EC in a Neoadjuvant Setting for Patients With Locally Advanced Luminal B HER2(-) or Triple Negative Breast Cancers.
- ClinicalTrials.gov ID
- NCT03356860
- Acronym / sponsor ID
- B-IMMUNE / ONCOGHdC2015_01
- Conditions
- Breast Cancer, Triple Negative Breast Cancer, Luminal B
- Keywords
- breast cancer, immunotherapy, anti-PD-L1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Grand Hôpital de CharleroiUniversity, hospital or other
- Collaborators
- Cliniques universitaires Saint-Luc- Université Catholique de Louvain
- Study start
- 13 Apr 2017 (actual)
- Primary completion
- 21 Nov 2022 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 29 Nov 2017 (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.
The study has a phase Ib and a phase II part.
- The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination with a dose- dense EC regimen in a neoadjuvant setting for early breast cancer.
- The phase II aims to explore the efficacy of durvalumab in combination with a dose-dense EC regimen in a neoadjuvant setting for early breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Durvalumab | Experimental | Drug: Paclitaxel, Drug: Epirubicin, Drug: Cyclophosphamide, Drug: DurvalumabPatients will received paclitaxel 80 mg/m2 IV weekly from week 1 to 12 and then an association of epirubicin 90 mg/m2 IV and cyclophosphamide 600 mg/m2 IV Q 2 weeks from week 14 to 20. Durvalumab will be administered at 1500 mg IV at week 14 and week 18. |
| Standard | Active comparator | Drug: Paclitaxel, Drug: Epirubicin, Drug: CyclophosphamidePatients will received paclitaxel 80 mg/m2 IV weekly from week 1 to 12 and then an association of epirubicin 90 mg/m2 IV and cyclophosphamide 600 mg/m2 IV Q 2 weeks from week 14 to 20. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Female and male aged > 18 years at time of study entry.
- Patient has T1-T4 any N, M0, operable breast cancer
- Confirmed invasive ductal, lobular, mixed or medullary breast carcinoma
- TNBC defined as negative oestrogen and progesterone receptors as per local laboratory testing and negative HER2 defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing
Key exclusion criteria (27 listed)
- Involvement in the planning and/or conduct of the study
- Previous enrolment in the present study
- Participation in another clinical study with an investigational product during the last 4 weeks
- Patient has locally recurrent or metastatic invasive BC
- History of another primary malignancy except for:
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 |
|---|---|---|
| PaclitaxelAlso: Taxol80mg/m2 IV weekly from week 1 to week12 | Drug | Durvalumab, Standard |
| EpirubicinAlso: Farmorubicine90 mg/m2 IV Q 2 weeks from week 14 to week 20 | Drug | Durvalumab, Standard |
| CyclophosphamideAlso: Endoxan600 mg/m2 IV Q 2 weeks from week 14 to week 20 | Drug | Durvalumab, Standard |
| DurvalumabAlso: MEDI4736Durvalumab 1500 mg IV at week 14 and 18 | Drug | Durvalumab |
Primary outcome
Adverse events
Time frame: 74 weeks
(serious) adverse event will be recorded
Pathological response
Time frame: 24 weeks
Rate of complete pathological responses will be evaluated as a surrogate endpoint to evaluate efficacy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Individual participant dataSharing planned: No
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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.
Javier Carrasco, MD, PhD principal investigator
GHdC
Jean-Luc Canon, MD principal investigator
GHdC
François Duhoux, MD, PhD principal investigator
Cliniques universitaires Saint-Luc (UCL)
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Paclitaxel, Epirubicin and Cyclophosphamide in people with Breast Cancer and Triple Negative Breast Cancer, run by Grand Hôpital de Charleroi at 4 sites in Belgium.
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 20 inclusion and 27 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: finished, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events (time frame: 74 weeks). The study lists 2 primary outcomes in all. 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 20 Nov 2024.