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
- Cancer
- Registration Number
- PACTR202108821955108
- Lead Sponsor
- F Hoffmann La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 4100
Inclusion criteria
Participants who are capable of giving signed informed consent as described in the protocol, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and in this protocol
• Participants (females, regardless of menopausal status, and males) who are age greater or equal to 18 years at the time of signing the Informed Consent Form
• Participants who have documented ER positive tumor by immunohistochemistry, as assessed locally on a primary disease specimen and defined as greater or equal to 1percent of tumor cells stained positive according to the ASCO/College of American Pathologists (CAP) guidelines (Allison et al. 2020).
• Participants who have documented HER2 negative tumor, as assessed locally on a primary disease specimen and defined according to ASCO/CAP guidelines (Wolff et al. 2018)
• 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 ER positivity and HER2 negativity
- Participants with bilateral synchronous invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER positivity and HER2 negativity
•Participants must have undergone definitive surgery of the primary breast tumor(s). With the exception of the situations described below, the margins of the resected specimen must be histologically free of invasive tumor and/or a component of ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the participant must undergo mastectomy to be eligible. Of note, participants with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.
– For participants who undergo mastectomy or wide local excision where deep margin abuts the pectoralis fascia, participants with microscopic positive margins are eligible as long as radiotherapy of the chest wall is administered prior to study entry. Participants with positive anterior margins may be eligible if there is no gross disease left behind (radiotherapy as per local guidelines).
– Participants with suspected metastasis in supraclavicular or internal mammary nodes should be treated in accordance with standard local guidelines.
– If given, radiation therapy (e.g., post-mastectomy or post-lumpectomy) should be administered according to standard guidelines.
• Participants who received or will be receiving 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 who are not candidates for adjuvant chemotherapy or decline chemotherapy are permitted.
Participants for whom resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade 1 or better (except alopecia, Grade less than or equal to 2 peripheral neuropathy, arthralgia, or other toxicities not considered a safety risk for the participant per the
Exclusion
Participants are excluded from the study if any of the following criteria apply:
• 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. Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment and a negative urine pregnancy test within 24 hours prior to study treatment initiation.
• Participants who have received treatment with investigational therapy within 28 days prior to initiation of study treatment or is currently enrolled in any other type of medical research judged by the Sponsor not to be 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, including any of the following: – History (within 2 years of screening) or presence of idiopathic bradycardia or resting heart rate less than 50 beats per minute at screening – History of angina pectoris or symptomatic coronary heart disease within 12 months prior to randomization – History of documented congestive heart failure (New York Heart Association Class II?IV) or cardiomyopathy – QT interval corrected through use of Fridericia’s formula greater than 470 ms for women greater than 450 ms for men based on mean value of triplicate ECGs, history of long or short QT syndrome, Brugada syndrome or known history of corrected QT interval prolongation, or torsades de pointes – Presence of an abnormal ECG that is clinically significant in the investigator’s opinion, including complete left bundle branch block, second- or third-degree heart block, or sick sinus syndrome o Participants with first-degree heart block may be considered for inclusion following consultation with a cardiologist and determination that no additional cardiac risks are present. o Participants with pacemakers to treat more severe heart blocks and other arrhythmias are permitted.
•Patients with history of well-controlled atrial fibrillation are eligible. – History (within 12 months) or presence of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as significant structural heart disease (e.g., severe left ventricular systolic dysfunction, restrictive cardiomyopathy, hypertrophic cardiomyopathy, infiltrative cardiomyopathy, moderate-to-severe valve disease), or family history of long QT syndrome)
Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia) should be corrected prior to enrollment.
• 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 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, non-melanoma skin carcinoma, or Stage I uterine cancer. – For participants with a history of other non-breast cancers within 3 years from the date of randomization and considered of very low risk of recurrence per investigator’s judgment (e.g., papillary thyroid
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method