A PHASE III, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY EVALUATING 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
- breastcancer with low levels of a protein called HER2HER2-negative breast cancer10006291
- Registration Number
- NL-OMON55972
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 11
• 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 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 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 (Allison et al. 2020).
• Participants who have documented HER2- tumor, as assessed locally on a
primary disease specimen and defined according to ASCO/CAP guidelines (Wolff et
al. 2018)
• Participants must have undergone definitive surgery of the primary breast
tumor(s)
• 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
anticancer 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 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.
•Participants with N1 disease are eligible if they meet additional criteria
as outlined in Table 5 (high risk)
• Any T and N2
• Any T and N3
• T4 and any N
• Participant who have Eastern Cooperative Oncology Group Performance (ECOG)
Performance Status 0, 1 or 2
• Participants who are able and willing to swallow and retain, and absorb oral
medication
• Participants who have adequate organ function
• For women of childbearing potential: participants who agree to remain
abstinent (refrain from heterosexual intercourse) or use contraception (women
assigned to tamoxifen must also agree to refrain from donating eggs) during
• 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 adjuvant therapy
• 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 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Invasive disease-free survival (IDFS), defined as the time from randomization<br /><br>to first occurrence of one of the following IDFS events;<br /><br>ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive<br /><br>breast cancer recurrence, distant recurrence, contralateral<br /><br>invasive breast cancer, and death from any cause. </p><br>
- Secondary Outcome Measures
Name Time Method