A study to evaluate the Efficacy and Safety of Adjuvant Giredestrant Compared with Physician's Choice of Adjuvant Endocrine Monotherapy in Patients with Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer.
- Conditions
- Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer.MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: LLTClassification code 10070577Term: Oestrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: PTClassification code 10083232Term: HER2 negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-000129-28-NL
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 4100
•Participants (females, regardless of menopausal status, and males) who are age >=18 years at the time of signing the Informed Consent Form
•Participants who have documented ER+ tumor by immunohistochemistry, as assessed locally on a primary disease specimen and defined as >=1% of tumor cells stained positive according to the ASCO/College of American Pathologists (CAP) guidelines or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines
•Participants who have documented HER2- tumor, as assessed locally on a primary disease specimen and defined according to ASCO/CAP guidelines or ESMO guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines
•Participants who have multicentric (the presence of two of more tumor foci within different quadrants of the same breast) and/or multifocal (the presence of two or more tumor foci within a single quadrant of the breast) breast cancer are also eligible if all examined tumors meet pathologic criteria for estrogen receptor (ER) positivity and HER2 negativity
•Participants must have undergone definitive surgery of their primary breast tumor(s) and axillary lymph nodes (ALND and/or SLNB)
•Participants who received adjuvant chemotherapy must have completed adjuvant chemotherapy prior to randomization. Participants may also have received neoadjuvant chemotherapy. A washout period of at least 21 days is required between last adjuvant chemotherapy dose and randomization
•Participants for whom resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better
•Participants have received (neo)adjuvant chemotherapy and/or had surgery and had no prior endocrine therapy (ET) are eligible, provided that they are enrolled within 12 months following definitive breast cancer surgery
•Participants who have confirmed availability of an untreated primary breast tumor tissue specimen suitable for biomarker testing (i.e., representative archival formalin-fixed, paraffin-embedded [FFPE] tissue block [preferred] or 15-20 slides containing unstained, freshly cut, serial sections), with associated deidentified pathology report is required. Although 15-20 slides are preferred, if only 10-14 slides are available, the individual may still be eligible for the study.
•Participants who received adjuvant chemotherapy or no chemotherapy must have the following:
o If no pathological involved nodes (pN0) primary tumor must be larger than 1 cm, and must fulfill at least one of the features as outlined in Table 5 (medium risk)
o Pathological node-positive disease (microscopic and/or macroscopic tumor involvement =pN1) and will be stratified in medium or high risk based on criteria defined in Table 5.
o Participants with positive ipsilateral internal mammary and/or supraclavicular lymph nodes are stratified as high risk, irrespective of axillary nodal involvement
•Participants with N1 disease are eligible if they meet additional criteria as outlined in Table 5 (high risk)
•Any pT and pN2
•Any pT and pN3
•pT4 and any pN
•Participants who received neoadjuvant chemotherapy must have residual disease in lymph nodes (=ypN1) after neoadjuvant chemotherapy and will be stratified to medium or high risk
•Participant who have Eastern Cooperative Oncology Group Performance (ECOG) Perfor
•Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 9 days after the final dose of giredestrant, or within the time period specified per local prescribing guidelines after the final dose of TPC
•Participants who have received treatment with investigational therapy within 28 days prior to initiation of study treatment or are currently enrolled in any other type of medical research that is scientifically or medically compatible with this study
•Participants receiving or planning to receive a CDK4/6i as (neo)adjuvant therapy. Short course of up to 12 weeks of neoadjuvant or adjuvant treatment with CDK4/6 inhibitor therapy prior to randomization is allowed
•Participants who have active cardiac disease or history of cardiac dysfunction
•Participants who have been diagnosed with Stage IV breast cancer
•Participants who have a history of any prior (ipsilateral and/or contralateral) invasive breast cancer or ductal carcinoma in situ (DCIS) Participants with a history of contralateral DCIS treated by only local regional therapy at any time may be eligible
•Participants who have a history of any other malignancy within 3 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, or Stage I uterine cancer
•Participants who have had more than 12 weeks of any prior endocrine treatment with selective ER modulators (e.g., tamoxifen), degraders or aromatase inhibitor (AI). Short course of neoadjuvant or adjuvant endocrine therapy (up to 12 weeks) is allowed
•Participants who have clinically significant liver disease consistent with Child-Pugh Class B or C, including active hepatitis (e.g., hepatitis B virus [HBV] or hepatitis C virus [HCV]), current alcohol abuse, cirrhosis, or positive test for viral hepatitis
•Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
•Participants who have a known allergy or hypersensitivity to any of the study drugs or any of their excipients
•Pre- and perimenopausal participants or male participants who have a known hypersensitivity to luteinizing hormone-releasing hormone (LHRH) agonists
•Participants who have a documented history of hemorrhagic diathesis, coagulopathy or thromboembolism (including deep venous thrombosis).
Note: Participants with prior superficial or vascular access-associated thrombosis can be included. However, if they have been on anticoagulation or intend to be for more than 3 months then inclusion into the study is not permitted
•Participants with renal dysfunction who require dialysis
•Participants who have had a major surgical procedure unrelated to breast cancer within 28 days prior to randomization
•Participants who have had a serious infection requiring oral or intravenous (IV) antibiotics within 14 days prior to screening or other clinically significant infection (e.g., COVID-19) within 14 days prior to screening
•Participants who have had any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study
•Participants who are unable or unwilling to comply with the requirements of the protocol in the opinion of the investigator
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