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

Phase 1

Recruiting

• Conditions: Previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC); MedDRA version: 20.0Level: LLTClassification code: 10027475Term: Metastatic breast cancer Class: 10029104; MedDRA version: 20.0Level: PTClassification code: 10075566Term: Triple negative breast cancer Class: 100000004864; MedDRA version: 20.0Level: PTClassification code: 10006198Term: Breast cancer recurrent Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-511850-34-00
• Lead Sponsor: Institut Jules Bordet

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-29
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 209

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 v1.1. 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, Agreement to provide tissue and blood samples for research purposes, Written informed consent must be given according to ICH/GCP, and national/local regulations before patient enrolment, Female, Inclusion criterion applicable to FRANCE only: Affiliated to the French Social Security System. Note: patients eligible for the Synergy trial are also eligible for the AURORA program (NCT02102165) or any other similar molecular screening program, aiming to understand the molecular aberrations in metastatic BC. Patients can be included in both trials in centres recruiting patients for AURORA or for any similar molecular screening program as long as tumour tissue and blood samples can be collected fo

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 o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified