A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of GDC-9545 Plus Palbociclib Compared with Anastrozole Plus Palbociclib for Postmenopausal Women with Estrogen Receptor-Positive and HER2-Negative Untreated Early Breast Cancer

Phase 1

• Conditions: Estrogen Receptor (ER)-Positive and HER2-Negative Untreated 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: EUCTR2020-001007-16-HU
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-08
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 215

Inclusion Criteria

-Postmenopausal women age >= 18 years
-Histologically confirmed operable or inoperable invasive breast carcinoma
ocT1c (>= 1.5 cm)-cT4a-c breast cancer at presentation
Primary tumor must be >= 1.5 cm in longest diameter by ultrasound.
-Measurable disease by ultrasound as defined per mRECIST
-Patients with multifocal tumors (more than one mass confined to the same quadrant as the primary tumor) if all lesions are sampled and confirmed as ER-positive/HER2-negative invasive breast cancer and at least one lesion is >= 1.5 cm in longest diameter by ultrasound
-Patients with multicentric tumors (multiple tumors involving more than one quadrant) if all discrete lesions are sampled and confirmed as ER-positive/HER2-negative invasive breast cancer and at least one lesion is >= 1.5 cm in longest diameter by ultrasound
-Candidate for neoadjuvant treatment and considered appropriate for endocrine therapy
-Willingness to undergo breast surgery after neoadjuvant treatment and to provide three mandatory tumor samples
-Documented ER-positive tumor in accordance to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (Allison et al.2020), assessed locally and defined as >= 1% of tumor cells stained positive on the basis of the most recent tumor biopsy
-Documented progesterone receptor status (positive or negative) as per local assessment
-Documented HER2-negative tumor in accordance to 2018 ASCO/CAP guidelines (Wolff et al. 2018), assessed locally on the most recent tumor biopsy
-Ki67 score >= 5% analyzed centrally or locally
-Eastern Cooperative Oncology Group Performance Status 0-1
-Adequate organ function

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 107

Exclusion Criteria

-Stage IV (metastatic) breast cancer
-Inflammatory breast cancer (cT4d)
-Bilateral invasive breast cancer
-History of invasive breast cancer, ductal carcinoma in situ or lobular carcinoma in situ and other malignancy within 5 years prior to screening
-Previous systemic or local treatment for the primary breast cancer currently under investigation
-History of any prior treatment with AIs, tamoxifen, selective estrogen receptor down regulator, or cyclin-dependent kinase 4 and 6 inhibitors
-Major surgery within 4 weeks prior to randomization
-Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis
-Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
-History of allergy to anastrozole, or palbociclib or any of its excipients
-Known issues with swallowing oral medication
-History of documented hemorrhagic diathesis, coagulopathy, or thromboembolism
-Active cardiac disease or history of cardiac dysfunction
-Current treatment with medications that are well known to prolong the QT interval
-Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery including gastric resection
-Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives prior to randomization
-Serious infection requiring oral or IV antibiotics, or other clinically significant infection within 14 days prior to screening
-Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified