A Phase I/II Study of Paclitaxel plus Carboplatin and Durvalumab (MEDI4736) with or without Oleclumab (MEDI9447) for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer

Institut Jules Bordet15 sites in 2 countries209 target enrollmentJune 6, 2024

DrugsOleclumab_IJB PACLITAXEL Durvalumab_IJB CARBOPLATIN

Overview

Phase: Phase 1/2
Intervention: Not specified
Conditions: Not specified
Sponsor: Institut Jules Bordet
Enrollment: 209
Locations: 15
Primary Endpoint: PHASE I: Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events (AEs). PHASE II: Clinical benefit (CB). CB is defined as a patient who achieved CR or PR or demonstrated SD at 24 weeks from the 1st dose of study drug administration based on RECIST v1.1
Status: Active, not recruiting
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

PHASE I: To confirm the safety of oleclumab in combination with paclitaxel, carboplatin and durvalumab in previously untreated, locally recurrent inoperable or metastatic TNBC patients.

PHASE II: To evaluate the clinical benefit of oleclumab in combination with paclitaxel, carboplatin and durvalumab in previously untreated, locally recurrent inoperable or metastatic TNBC patients by the comparing the clinical benefit rate (CBR) at 24 weeks from the 1st dose of study drug administration between patients treated with or without the anti-CD73 antibody oleclumab.

Registry

euclinicaltrials.eu

Start Date

June 6, 2024

End Date

TBD

Last Updated

10 months ago

Study Type

Interventional clinical trial of medicinal product

Sex

Female

Investigators

Sponsor

Institut Jules Bordet

Responsible Party

Principal Investigator

CTSU

Scientific

Institut Jules Bordet

Eligibility Criteria

Inclusion Criteria

•Age of ≥ 18 years
•Provision of an archived FFPE diagnostic biopsy or surgical primary tumour sample (or at least 20 unstained slides, freshly cut for the purposes of the study). In case of neoadjuvant treatment (before surgery), the diagnostic biopsy is preferable.
•At least 6 months elapsed between the completion of surgical and/or systemic treatment with curative intent (e.g., the date of primary breast tumour surgery or the date of last adjuvant chemotherapy administration (radiotherapy is not included), whichever occurred last) and first documented local or distant disease recurrence (NOTE: not applicable for de-novo metastatic disease)
•At least one measurable disease based on RECIST v1.
•Tumour lesions in a previously irradiated area are considered measurable, if progression has been demonstrated in such lesions
•Adequate organ function: a) Absolute neutrophil count (ANC) ≥ 1500/µl (without the addition of growth factors) b) Platelets [PLT] ≥ 100000/µl (without the addition of growth factors/prior transfusions) c) Hemoglobin (Hb) ≥ 10 g/dl (without the addition of growth factors/prior transfusions) d) Creatinine ≤ 1.5 x upper limit of normal (ULN) OR estimated glomerular filtration rate (eGFR) ≥ 60 ml/min as calculated using the method standard for the institution. If eGFR is lower than 60 ml/min, a 24-hour urine creatinine clearance can be performed to rule out an underestimation of the eGFR. e) Total serum bilirubin (TBL) ≤ 1.5 x ULN unless the subject has documented Gilbert syndrome in which case up to 3 x ULN is acceptable f) Aspartate and alanine aminotransferase (AST/ALT) ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤ 5 x ULN. g) International Normalized Ratio (INR) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as INR and activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
•Performance status (PS) of 0 or 1 on the ECOG Performance scale
•Female subjects of childbearing potential (FSCP) must be willing to use one highly effective method of contraception (detailed at protocol section 6.6.) for the course of the study through 6 months after the last study drug administration. FSCP must have a negative serum pregnancy test done within the 28 days before treatment start. FSCP are those who have not been surgically sterilized or have not been free of menses for at least 1 year.
•Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
•Absence of any concurrent illness that would preclude the evaluation of safety

Exclusion Criteria

•Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: a) Patients with vitiligo or alopecia b) Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement c) Any chronic skin condition that does not require systemic therapy d) Patients without active disease in the last 5 years may be included but only after consultation with the sponsor e) Patients with celiac disease controlled by diet alone
•Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases with local treatment (stereotactic radiosurgery or whole brain radiation therapy) may participate provided they have stable brain metastases on a recent brain MRI (performed during the 2 weeks prior inclusion) and have measurable disease outside the CNS. Note: Known brain metastases are considered active (and not eligible for trial), if any of the following criteria are applicable: a) Recent brain imaging demonstrates progression of existing and/or appearance of new lesions b) Neurological symptoms attributed to brain metastases have not returned to baseline c) Steroids were used for management of symptoms related to brain metastases within 14 days of enrolment d) Completion of local therapy for brain metastases within 28 days of enrolment
•Major surgical procedure (as defined by the principal investigator) within 28 days prior to enrolment. Note: Local surgery of isolated lesions for palliative intent is acceptable
•Uncontrolled intercurrent illness, including but not limited to, a) Symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia. Patients previously treated with anthracyclines are eligible if a recent cardiac work up (< 6 months) demonstrated a normal left ventricular ejection fraction (LVEF≥50%). b) Interstitial lung disease c) Serious chronic gastrointestinal conditions associated with diarrhoea d) Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
•Past medical conditions, including, a) Class II-IV congestive heart failure b) Myocardial infarction within 12 months prior enrolment, c) Deep vein thrombosis (DVT) or thrombo-embolic event within 12 months prior to enrolment d) History of stroke or transient ischemic attack requiring medical therapy e) Intra-abdominal inflammatory process within the last 12 months prior to enrolment such as, but not limited to, diverticulitis, peptic ulcer disease, or colitis f) History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis g) 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 IP and of low potential risk for recurrence, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated carcinoma in situ without evidence of disease h) Status post allogeneic bone marrow transplantation or solid organ transplantation
•Pregnant or lactating women.
•Exclusion criterion applicable to FRANCE only: Vulnerable persons according to the article L.1121-6 of the Public Health Code, adults who are the subjects of a measure of legal protection or unable to express their consent according to article L.1121-8 of the Public Health Code.
•Current or prior treatment with immunosuppressive medication within 14 days prior to enrolment. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) b) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent c) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication
•Any live, attenuated vaccine administered within 28 days prior to enrolment or anticipation that such a live attenuated vaccine will be required during the study
•Chronic daily treatment with non-steroidal anti-inflammatory drug (NSAID) (occasional use for the symptomatic relief of medical conditions, for example, headache, fever is allowed)

Outcomes

Primary Outcomes

PHASE I: Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events (AEs). PHASE II: Clinical benefit (CB). CB is defined as a patient who achieved CR or PR or demonstrated SD at 24 weeks from the 1st dose of study drug administration based on RECIST v1.1

Secondary Outcomes

PHASE I: Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events (AEs) including Dose limiting toxicities (DLTs) as defined per protocol
PHASE II: 1) Objective Response. OR is defined as a patient (in the intent-to treat population) who achieved a CR or PR as best overall response (BOR) based on RECIST v1.1.
2) Duration of Response. DOR is defined as the time from documentation of first tumour response to disease progression based on RECIST v1.1.
3) Progression Free Survival. PFS is defined as the time from 1st study drug administration to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurs first. (Subjects who are alive and progression free at the time of analysis will be censored at the time-point of their last tumour assessment by imaging.)
4) Overall Survival. OS is defined as the time from 1st study drug administration to death due to any cause. (Subject without documented death at the time of the analysis will be censored at the date of the last follow-up.)
5) Frequency, duration and severity of AEs assessment based on CTCAE 5.0