A Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Giredestrant Plus Palbociclib Compared With Anastrozole Plus Palbociclib for Postmenopausal Women With Estrogen Receptor-Positive and HER2-Negative Untreated Early Breast Cancer (coopERA Breast Cancer)
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| ClinicalTrials.gov Identifier: NCT04436744 |
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Recruitment Status :
Completed
First Posted : June 18, 2020
Last Update Posted : January 14, 2022
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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Brief Summary:
This is a randomized, multicenter, open-label, two-arm, Phase II study to evaluate the efficacy, safety, and pharmacokinetics of giredestrant versus anastrozole (in the window-of-opportunity phase) and giredestrant plus palbociclib compared with anastrozole plus palbociclib (in the neoadjuvant phase) in postmenopausal women with untreated, estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, early breast cancer.
The study consists of a screening period of up to 28 days, a window-of-opportunity phase for 14 days, followed by a neoadjuvant treatment phase for 16 weeks (four 28-day cycles), surgery, and an end of study visit (28 days after the final dose of study treatment).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Early Breast Cancer | Drug: Giredestrant Drug: Anastrozole Drug: Palbociclib Procedure: Surgery | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 221 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Multicenter, Open-Label, Two-Arm, Phase II, Neoadjuvant Study Evaluating 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 |
| Actual Study Start Date : | September 4, 2020 |
| Actual Primary Completion Date : | July 6, 2021 |
| Actual Study Completion Date : | November 24, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
| Experimental: Giredestrant + Palbociclib |
Drug: Giredestrant
During the window-of-opportunity phase (first 2 weeks) giredestrant will be taken orally once per day (QD) as a single agent. During the neoadjuvant treatment phase, giredestrant will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib.
Other Names:
Drug: Palbociclib During the neoadjuvant treatment phase, palbociclib 125 mg will be taken orally QD on Days 1-21 of a 28-day cycle for a total of 4 cycles. Procedure: Surgery Surgery must be performed within a maximum of 14 days after the final cycle in the neoadjuvant treatment phase and ideally should occur as soon as possible after the last dose of study treatment. |
| Active Comparator: Anastrozole + Palbociclib |
Drug: Anastrozole
During the window-of-opportunity phase (first 2 weeks), anastrozole 1 mg will be taken orally QD as a single agent. During the neoadjuvant treatment phase, anastrozole 1 mg will be taken orally QD on Days 1-28 of each 28-day cycle for a total of 4 cycles, in combination with palbociclib. Drug: Palbociclib During the neoadjuvant treatment phase, palbociclib 125 mg will be taken orally QD on Days 1-21 of a 28-day cycle for a total of 4 cycles. Procedure: Surgery Surgery must be performed within a maximum of 14 days after the final cycle in the neoadjuvant treatment phase and ideally should occur as soon as possible after the last dose of study treatment. |
Primary Outcome Measures :
- Change in Ki67 Scores from Baseline to Week 2 [ Time Frame: Baseline and Week 2 ]
Secondary Outcome Measures :
- Overall Response Rate by Ultrasound, Defined as the Percentage of Participants with a Complete Response (CR) or Partial Response (PR), as Determined by the Investigator According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ Time Frame: Baseline and Cycle 4 Day 1 (1 cycle is 28 days) ]
- Complete Cell Cycle Arrest Rate, Defined as the Percentage of Participants with Centrally Assessed Ki67 Scores ≤2.7% Stained Nuclei Upon Treatment at Week 2 [ Time Frame: Week 2 ]
- Incidence and Severity of Adverse Events, with Severity Determined in Accordance to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Change from Baseline in Respiratory Rate Over Time [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Change from Baseline in Pulse Rate Over Time [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Change from Baseline in Systolic Blood Pressure Over Time [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Change from Baseline in Diastolic Blood Pressure Over Time [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Change from Baseline in Body Temperature Over Time [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Number of Participants with Clinical Laboratory Abnormalities in Hematology Test Parameters [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Number of Participants with Clinical Laboratory Abnormalities in Blood Chemistry Test Parameters [ Time Frame: From Baseline until 28 days after final dose of study treatment (up to 24 weeks) ]
- Plasma Concentration of Giredestrant at Specified Timepoints [ Time Frame: Cycle 0 Days 1 and 15, Cycle 2 Day 1 (1 cycle is 28 days), and End of Study Visit (up to 24 weeks) ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Postmenopausal women age ≥18 years
- Histologically confirmed operable or inoperable invasive breast carcinoma
- 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 estrogen receptor (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 human epidermal growth factor receptor-2 (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
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 aromatase inhibitors (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
- Known HIV infection
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04436744
Locations
Show 74 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT04436744 |
| Other Study ID Numbers: |
WO42133 2020-001007-16 ( EudraCT Number ) |
| First Posted: | June 18, 2020 Key Record Dates |
| Last Update Posted: | January 14, 2022 |
| Last Verified: | January 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Palbociclib Anastrozole Antineoplastic Agents Protein Kinase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Hormonal Aromatase Inhibitors Steroid Synthesis Inhibitors Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |