Phase 1 / 2 study of amcenestrant (SAR439859) single agent and in combination with other anti-cancer therapies in postmenopausal women with estrogen receptor positive advanced breast cancer
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Cancer
- Registration Number
- EUCTR2017-000690-36-PL
- Lead Sponsor
- SANOFI-AVENTIS RECHERCHE ET DEVELOPPEMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 339
-Participants must be postmenopausal women
-Histological diagnosis of breast adenocarcinoma
-Locally advanced or metastatic disease
-Either primary tumor or any metastatic site to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor
-Participants must have been previously treated with at least 6 months
of endocrine therapy for advanced disease:
- Dose Escalation study parts:
- Arm #3 - Part F and Arm #5 - Part J: up to 2 prior lines of
either single endocrine therapy and/or endocrine-based therapy
- Arm #4 -H: up to 2 prior lines of either single endocrine
therapy and/or endocrine-based therapy (exemestane not allowed)
- Dose Expansion study parts:
- Arm #2: - Part D: no more than 2 prior lines of advanced
endocrine therapy for advanced disease are allowed
- Arm #3, - Part G: patients must have received and progressed
on the combination of Aromatase Inhibitors (AI) + CDK4/6 inhibitor as
the first line (1L)
treatment for advanced disease
- Arm #4 - Part I: participants must have received and
progressed on the combination of Aromatase Inhibitors (AI) +CDK4/6
Inhibitor as the first line (1L)
treatment for advanced disease (exemestane not allowed)
- Arm#5: - Part K: up to 1 prior line of a single endocrine
therapy for advanced disease
Note: Additional patients who relapsed while on previous adjuvant
endocrine therapy that was initiated =24 months ago, or relapsed < 12
months after completion of adjuvant endocrine therapy are also allowed
for Arms #2, #3, #4, and #5 (Parts C, D, F, G, H, I, J and K).
- Participants previously treated with chemotherapy for advanced
disease: no more than 3 prior chemotherapeutic regimens in Arm #1
Part A, and no more than 1 prior chemotherapeutic regimen in Arms #1,
#2, #3, #4, and #5 (Parts B, C, D, F, H and J respectively); prior
chemotherapy for advanced disease is not allowed in dose expansion of
Arms #3, #4, and #5 (Part G, I and K respectively).
-Measurable lesion
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 189
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150
-Medical history or ongoing gastrointestinal disorders that could affect absorption of oral study drugs (including difficulties with swallowing capsules)
-Participants with any other cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or any other cancer from which the participant has been disease free for >3 years)
-Participants with known brain metastases
-Treatment with anticancer agents (including investigational drugs) less than 2 weeks before first study treatment starts (less than 4 weeks if the anticancer agents were antibodies)
- Prior treatment with another selective ER down-regulator (SERD)
- Dose Escalation study parts (Parts F, H and J): SERDs are not allowed
except for fulvestrant which will need a washout of at least 6 weeks
prior to the first study drug administration
- Dose Expansion study parts (Parts G, I and K): prior (last) treatment
with any SERD including fulvestrant will not be allowed
-Inadequate hematological and biochemical lab tests
-Participants with Gilbert disease
-Treatment with HIV-antiviral, antifungal and antioxidant agents less than 2 weeks before study treatment starts
-Treatment with strong P450 (CYP) 3A inducers within 2 weeks before
first study treatment
- Treatment with OATP1B1/B3 sensitive substrates and which cannot be
replaced
- Arm#2 Treatment with strong CYP3A inhibitors within 2 weeks before
first study treatment starts
-More than one prior advanced cyclin-dependent kinase (CDK) 4/6 inhibitor based therapy in Arm #1 (Parts A and B), Arm #2 (Part C), and Arm #3 (Parts F and G), and Arm#4 (Part H).
- Arm #2, #3, #4 and #5 (Parts C, D, F, G, H, I, J and K) only: participants with concurrent or history of pneumonitis
- Arm #3, #4 and #5 (Parts F, G, H, I, J and K) only: prior treatment therapies that target the PI3K axis (mTOR inhibitors, AKT inhibitors, PI3K inhibitors)
- Arm #3 and #4 (Parts F, G, H and I) only: participants with diabetes mellitus type-I or uncontrolled diabetes mellitus type-II: ie, fasting plasma glucose = 140mg/dl (7.7 mmol/l) or HbA1C > 6.2%
- Arm #3 and #4 (Parts F, G, H and I) only: history of severe cutaneous reaction (eg.Stevens-Johnson syndrome [SJS], erythema multiforme [EM]), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms [DRESS].
- Arm #3 (Parts F and G) only: ongoing osteonecrosis of jaw
- Arm #4 (Parts H and I) only: any active, untreated or uncontrolled infection (e.g. viral, bacterial, fungal etc.)
- Arm #4 (Parts H and I) only: participants with active and uncontrolled stomatitis, angioedema due to concomitant treatment with ACE inhibitors, impaired wounds
- Arm #4 (Parts H and I) only: uncontrolled hypercholesterolemia, hypertriglyceridemia and hyperglycemia in non-diabetic participants
- Arm #4 (Parts H and I) only: treatment with strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers and/or P-gp inhibitors within 2 weeks before the first study treatment administration or 5 elimination half-lives, whichever is the longest
- Arm #5 (Parts J and K) only: history or current (controlled/not controlled) venous thromboembolism (i.e. deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral venous sinus thrombosis (CVST)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method