C50 Cancer de mama
Conditions
Interventions
Participants in the experimental arm will receive giredestrant 30 mg orally (PO) once a day (QD) on Days 1-28 of each 28-day cycle. Giredestrant will be administered in the clinic on Day 1 of Cycle 1,
it will be taken at home on all non-clinic visit days. - Participants in the control arm will receive intramuscular (IM) fulvestrant 500 mg IM on Days 1 and 15 of Cycle 1 and on Day 1 of each subseque
Sponsors
F. HOFFMANN-LA ROCHE LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 6 months Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Adequate organ function as defined by the following criteria: o ANC >/= 1.5 X 10^9/L (1500/uL) o Platelet count >/= 100 x 10^9/L (100,000/uL) o Hemoglobin >/= 90 g/L (9 g/dL) o AST and serum ALT </= 3 x upper limit of normal (ULN); for participants with liver metastases: AST and ALT </= 5 x ULN o Serum bilirubin </= 1.5 x ULN; for patients with Gilbert syndrome: </= 3 x ULN o Estimated creatinine clearance ? 30 mL/min as calculated per institutional guidelines. INR (or PT) < 1.5 x ULN and PTT (or aPTT) < 1.5 x ULN (except for participants receiving anticoagulation therapy) Resolution of all toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade = 1 (e
Exclusion criteria
Exclusion criteria: 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 Active cardiac disease or history of cardiac dysfunction Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral infection or other hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]), current alcohol abuse, or cirrhosis or positive test for viral hepatitis Known HIV infection. Screening HIV test should be performed, as allowed per local regulations. Serious infection requiring oral or IV antibiotics, or other clinically significant infection within 14 days prior to randomization Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery including gastric resection, potentially affecting enteral absorption, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea Malabsorption syndrome or other condition that would interfere with enteral absorption Inability or unwillingness to swallow pills or receive IM injections Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the individual's safe participation in and completion of the study Known allergy or hypersensitivity to any of the study drugs or any of their excipients For pre/perimenopausal female or male participants: known hypersensitivity to LHRH agonists or any of their excipients Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 98 days after the final dose of study treatment (based on local prescribing information for fulvestrant, patients may be advised to use an effective means of contraception for up to 2 years after the last dose of fulvestrant)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determined by the investigator according to RECIST v1.1, or death from any cause during the study (whichever occurs first) NAME OF THE RESULT: Progresion Fre survivial (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to first occurrence of progression disease (PD);The time from randomization to death from any cause NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Determined by the investigator according to RECIST v1.1, or death from any cause during the study (whichever occurs first) NAME OF THE RESULT: Progresion Fre survivial (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to first occurrence of progression disease (PD);The time from randomization to death from any cause NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study;Measure of proportion of participants with a Complete Response or Partial Response, as determined by the investigator according to RECIST v1.1 NAME OF THE RESULT: Confirmed objective response rate (cORR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: On two consecutive occasions = 4 weeks apart;Measure of time from the first occurrence of a documented objective response to Progress Disease. NAME OF THE RESULT: Duration of response (DOR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: When determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first);Measure of proportion of participants with stable disease for = 24 weeks or a complete response or partial response,. NAME OF THE RESULT: Clinical benefit rate (CBR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: As determined by the investigator according to RECIST v1.1;Measure of time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first) NAME OF THE RESULT: Time to chemotherapy (TTCtx) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The start date of chemotherapy or death from any cause (whichever occurs first);BPI-SF = Brief Pain Inventory-Shor | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Costa Rica, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Kenya, Korea South, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Singapore, Slovenia, South Africa, Spain, Taiwan, Thailand, Turkey, United States
Contacts
Public ContactLuisa Leonor Garcia
ROCHE FARMA (PERU) S.A.
Outcome results
None listed