A PHASE III, RANDOMIZED, OPEN-LABEL STUDY EVALUATING EFFICACY AND SAFETY OF GIREDESTRANT COMPARED WITH FULVESTRANT, BOTH COMBINED WITH A CDK4/6 INHIBITOR, IN PATIENTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER WITH RESISTANCE TO PRIOR ADJUVANT ENDOCRINE THERAPY
- Conditions
- C50 Cancer de mama
- Registration Number
- PER-040-23
- Lead Sponsor
- F. HOFFMANN-LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Without startig enrollment
- Sex
- All
- Target Recruitment
- 0
Signed Informed Consent Form
Age >/= 18 years at time of signing Informed Consent Form
Locally advanced or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
Documented ER+ tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) (Allison et al. 2020) or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines, defined as = 1% of tumor cells stained positive, assessed locally based on the most recent tumor biopsy (or archived tumor sample)
Documented HER2- tumor according to ASCO/CAP (Wolff et al. 2023) or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines, assessed locally based on the most recent tumor biopsy (or archived tumor sample)
Confirmed ESR1 mutation status (mutation detected [ESR1m] vs. no mutation detected [ESR1nmd]) in baseline ctDNA, as assessed through central laboratory testing of a blood sample freshly collected at screening, using the investigational FMI F1LCDx assay. A valid central testing result using investigational F1LCDx is always required; in localities where FMI central testing is not available, samples will be submitted to an alternative, Sponsor-designated central laboratory. Participants without a valid ESR1 mutation status central result (i.e., unknown ESR1 mutation status that cannot be classified as ESR1m or ESR1nmd) are not eligible.
Consent to provide and confirmed availability of the most recently collected and representative tumor tissue specimen suitable for biomarker testing with associated pathology (i.e., archived formalin-fixed paraffin-embedded tissue block [preferred] or 15-20 slides containing unstained, freshly cut, serial sections). See Section 8.7 and the laboratory manual for specimen requirements.
Participants who have relapsed with prior standard adjuvant ET with an AI (i.e., anastrozole, letrozole, or exemestane) and/or a SERM (i.e., tamoxifenor toremifene), on-treatment after = 12 months or off-treatment within 12 months of completion (i.e., treatment-free interval < 12 months).
No history of systemic anti-cancer therapy for locally advanced or metastatic disease.
Measurable disease as defined per RECIST v.1.1 or non-measurable bone-only disease which must be evaluable defined as having at least one predominantly lytic bone lesion confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) which can be followed (soft tissue component not required).
Consid
Disease recurrence during the first 12 months of adjuvant ET
Prior systemic therapy for metastatic breast cancer (e.g., prior chemotherapy, immunotherapy, or biologic therapy for locally advanced unresectable or metastatic disease)
Prior treatment with a SERD (e.g., fulvestrant, novel oral), proteolysis targeting chimera, complete ER antagonist (CERAN), or novel SERM (other than tamoxifen, toremifene)
Treatment with any investigational therapy within 28 days prior to randomization, or within 5 half-lives of the investigational drug(s), whichever is longer
Radiotherapy or any other anti-cancer therapy within 2 weeks before randomization
Major surgical procedure or significant traumatic injury within 28 days prior to randomization
Exposure to strong CYP3A4 inhibitors, strong CYP3A4 inducers, and moderate CYP3A inducers (for participants who will receive abemaciclib only) within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term (including massive uncontrolled effusions [pleural, pericardial, peritoneal] or pulmonary lymphangitis) appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines
History of other malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence including, but not limited to, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, papillary thyroid cancer treated with surgery, or Stage I endometrial cancer. The Medical Monitor is available for consultation
Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Determined by the investigator according to RECIST v1.1, or death from any cause during the study (whichever occurs first)<br> NAME OF THE RESULT: Progresion Fre survivial (PFS)<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: From randomization to first occurrence of progression disease (PD) ;The time from randomization to death from any cause<br> NAME OF THE RESULT: Overall Survival (OS)<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: Throughout the study
- Secondary Outcome Measures
Name Time Method