Study that tested S64315 plus different standard treatments in patients with breast cancer

Phase 1

• Conditions: ocally advanced or metastatic breast cancer.; MedDRA version: 21.1Level: LLTClassification code 10072740Term: Locally advanced breast cancerSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000998-23-ES
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-26
• Study Completion: 2020-12-08
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

In Arm 1: S64315 + paclitaxel
-Histologically confirmed locally advanced or metastatic TNBC or HR+/Her2- (HR+ (Estrogen or Progesterone) > 10% and Her2- (score 0 or 1 by immunochemistry), FISH BC (Fluorescence In Situ Hybridization) negative if IHC (immuno-histochemistry) score 2):
TNBC: no more than 2 prior chemotherapeutic regimens in the locally advanced or metastatic setting
HR+/Her2-: no more than 2 prior chemotherapeutic regimens and no more than 1 prior PI3K inhibitor (PIKi) in the locally advanced or metastatic setting

In Arm 2: S64315 + eribulin
-Histologically confirmed locally advanced or metastatic TNBC or HR+/Her2- BC (HR+ (Estrogen or Progesterone) > 10% and Her2- (score 0 or 1 by immunochemistry), FISH (Fluorescence In Situ Hybridization) negative if IHC (immuno-histochemistry) score 2):
TNBC: no more than 2 prior chemotherapeutic regimens in the locally advanced or metastatic setting
HR+/Her2-: no more than 2 prior chemotherapeutic regimens and no more than 1 prior PI3Ki in the locally advanced or metastatic setting
-No prior exposure to eribulin in the adjuvant, neoadjuvant or metastatic setting

In Arm 3: S64315 + fulvestrant
-Histologically confirmed locally advanced or metastatic HR+/Her2- BC: (HR+ (Estrogen or Progesterone) > 10% and Her2- (score 0 or 1 by mmunochemistry), FISH (Fluorescence In Situ Hybridization) negative if IHC (immuno-histochemistry) score 2)
No more than two prior lines of hormonal therapy in the locally advanced or metastatic setting
Prior treatment with CDK4/6 inhibitor (CDK4/6i) is permitted
Prior treatment with PI3K inhibitor (PI3Ki) is permitted
Patients for whom endocrine therapy (e.g., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at the time of entry into the study, as per national or local treatment guidelines
-Post-menopausal women

For all patients:
-Patient must have at least one measurable lesion, as defined by revised RECIST v1.1, 2009
-Estimated life expectancy = 12 weeks
-Eastern Cooperative Oncology Group (ECOG) performance status = 1
-Adequate haematological function based on the last assessment performed within 7 days prior to the first IMP administration.
-Adequate renal function based on the last assessment performed within 7 days prior to the first IMP administration.
-Adequate hepatic function based on the last assessment performed within 7 days prior to the first IMP administration.
-Serum CK/CPK = 2.5 ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 116

Exclusion Criteria

-Only for Arm 1 and 2: Pregnant and lactating women
-Patients who have not recovered from toxicity of previous anticancer therapy, including grade = 2 non-haematologic toxicity, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.00), prior to the first IMP administration Certain toxicities will not be considered in this category (e.g. alopecia)
-Severe or uncontrolled active acute or chronic infection
-Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active viral or other hepatitis or cirrhosis
-Medical history of acute or chronic pancreatitis
-Unresolved diarrhoea = CTCAE Grade 2 or presence of medical condition associated with chronic diarrhoea (such as irritable bowel syndrome, inflammatory bowel disease)
-Clinically significant cardiac dysfunction (including NYHA Class = II heart failure, left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiography or Multi Gated Acquisition Scan (MUGA))
-Uncontrolled arterial hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg despite treatment)
-Acute coronary syndrome including unstable angina pectoris (anginal symptoms at rest), new onset angina, acute myocardial infarction, coronary artery bypass graft (CABG) within 3 months prior to starting study treatment
-Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, atrial fibrillation), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
-Congenital or substance-induced long QT defined as QTc interval > 450 ms for males and > 470 ms for females according to Frederica’s formula
-Troponin (I or T) > ULN
-Patients with coagulopathy that will increase the risk of bleeding complications according to investigator’s judgment (e.g. disseminated intravascular coagulation)
-Known hypersensitivity to paclitaxel /eribulin /fulvestrant or S65315 including excipients of the liposomal vehicle, eggs or soybean
-Only for Arm 1 and Arm 2: Evidence of peripheral neuropathy = CTCAE grade 2
-Major surgery (involving a risk to the life of the patient) within 4 weeks prior to the first dose of IMP, or patients who have not recovered from side effects of the surgery
-Any radiotherapy within 2 weeks before the first dose of IMP (except for palliative radiotherapy at localised lesions)

Study & Design

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