Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04436744
Other study ID # WO42133
Secondary ID 2020-001007-16
Status Completed
Phase Phase 2
First received
Last updated
Start date September 4, 2020
Est. completion date November 24, 2021

Study information

Verified date January 2023
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


Read more »

Study Design


Related Conditions & MeSH terms


Intervention

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.
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.
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.

See more »

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Germany,  Hungary,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  Ukraine, 

Outcome

Type Measure Description Time frame Safety issue
Primary Relative Percent Change in Ki67 Scores From Baseline to Week 2 Ki67 is a proliferation biomarker with prognostic value in ER-positive breast cancer. Ki67 scores were centrally assessed with immunohistochemistry and defined as a percentage of positively stained tumor cell nuclei among the total number of tumor cells assessed, with a potential range of 0-100%. A score of 0% indicates no tumor cell nuclei with Ki67 staining and a score of 100% indicates all tumor cell nuclei are positively stained with Ki67. The relative percentage change was calculated using Ki67 scores at Baseline and Week 2. Relative Percent Change was defined as Week 2 Ki67 percentage score/Baseline Ki67 percentage score*100. A smaller value of relative percentage change indicates improvement. Baseline, Week 2
Secondary Overall Response Rate (ORR) by Ultrasound as Determined by the Investigator ORR was 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). Ultrasound and clinical exam were used to assess response. CR per mRECIST was defined as the disappearance of all target lesions. PR per mRECIST was defined as at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. An estimate of ORR and its 95% confidence interval (CI) was calculated using the Clopper-Pearson method. Baseline up to Cycle 4 Day 1 (each cycle is 28 days)
Secondary Complete Cell Cycle Arrest (CCCA) Rate at Week 2 CCCA was defined as the percentage of participants with centrally assessed Ki67 scores =2.7%. The CCCA rate at Week 2 was summarized. Week 2
Secondary Number of Participants With Adverse Events (AEs) With Severity Determined in Accordance With National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) AE is any untoward medical occurrence in clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable & unintended sign, symptom/disease temporally associated with use of a medicinal product, whether or not related to medicinal product. Preexisting conditions which worsen during a study also considered as AEs. Severity of AEs was determined per NCI CTCAE v5.0. Grade 1: Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2: Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3: Severe/medically significant, but not immediately life-threatening: hospitalization/prolongation of hospitalization indicated; disabling/limiting self-care activities of daily living; Grade 4: Life-threatening consequences/urgent intervention indicated; Grade 5: Death related to AE. From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Secondary Change From Baseline in Respiratory Rate Over Time Respiratory rate was measured while the participant was in a seated position. Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Secondary Change From Baseline in Pulse Rate Over Time Pulse rate was measured while the participant was in a seated position. Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Secondary Change From Baseline in Systolic Blood Pressure Over Time Systolic blood pressure was measured while the participant was in a seated position. Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Secondary Change From Baseline in Diastolic Blood Pressure Over Time Diastolic blood pressure was measured while the participant was in a seated position. Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Secondary Change From Baseline in Body Temperature Over Time Baseline; Cycles 1-2: Day 1 and Day 15; Cycles 3-4: Day 1; day of surgery (up to 2 weeks after the final dose of study treatment [approximately Week 18]) and end of study (up to approximately 24 weeks)
Secondary Number of Participants With Shifts in Hematology Test Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline Hematology test parameters were measured per NCI CTCAE v5.0. Grade 0 is normal, and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Number of participants with shift in the hematology values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. A marked reference range for hemoglobin 12.3-15.3 grams per deciliter (g/dL), lymphocytes absolute (Abs) 1.0-4.8 10^3/microliters (uL), neutrophils total, Abs, 1.8-8.5 10^3/uL, platelet 100-450 10^9/liter (L), total leukocyte 4.4-11 10^9/L. From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Secondary Number of Participants With Shifts in Blood Chemistry Parameters From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 at Post-baseline Blood chemistry parameters were measured per NCI CTCAE v5.0. Grade 0=normal, and Grades 1 to 4 represent worsening levels of parameter outside of normal range in the specified direction of abnormality (high & low are above & below the range, respectively). Number of participants with shift in blood chemistry values from grade 0-2 at baseline to grade 3-4 at post-baseline were reported. Marked reference range for albumin 32-45 grams per liter (g/L), alkaline phosphatase 20-130 units per liter (U/L), serum glutamic pyruvic transaminase (SGPT)/ alanine transaminase (ALT) 4-36 U/L, serum glutamic oxaloacetic transaminase (SGOT)/ aspartate transaminase (AST) 8-33 U/L, calcium 2.3-2.74 millimoles per liter (mmol/L), cholesterol 3.88-6.47mmol/L, creatinine 6-12 milligrams per liter (mg/L), glucose 3.9-6.1 mmol/L, potassium 3.5-5.0 mmol/L, sodium 135-147 mmol/L, bilirubin 2-21 micromoles per liter (µmol/L), triglycerides 0.11-2.15 mmol/L, & uric acid 2.7-7.3 milligrams per deciliter (mg/dL). From baseline up to 28 days after the last dose (up to approximately 24 weeks)
Secondary Plasma Concentration of Giredestrant at Specified Timepoints Window of Opportunity Phase: Day 1 (3 hours Postdose) and Day 15 (Predose) during Cycle 0 (the 15-day period in Window of Opportunity Phase is called Cycle 0 for PK analysis); Neoadjuvant Phase: Cycle 2 Day 1, Predose
See also
  Status Clinical Trial Phase
Withdrawn NCT04538833 - GM1 in the Treatment of Neurotoxicity Induced by Albumin-bound Paclitaxel Phase 2
Completed NCT02187744 - A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04) Phase 3
Terminated NCT01155063 - Evaluating The Safety Of Exemestane Following 2-3 Years Of Adjuvant Tamoxifen Therapy In Postmenopausal Early Breast Cancer Patients N/A
Recruiting NCT03949634 - Cardiac Safety and Efficacy for Early-stage Breast Cancer Patients Treated With Pegylated Liposomal Doxorubicin(PLD) Phase 3
Active, not recruiting NCT05730647 - Prospective Observational Study of Adjuvant Hormone Treatment in Estrogen-receptor Positive Premenopausal Early Breast Cancer Patients
Terminated NCT01919229 - A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1) Phase 2
Active, not recruiting NCT04293393 - Neoadjuvant Study Chemotherapy vs Letrozole + Abemaciclib in HR+/HER2- High/Intermediate Risk Breast Cancer Patients Phase 2
Completed NCT00713141 - Evaluation of Brain Function Before and After Standard Chemotherapy for Early Breast Cancer N/A
Recruiting NCT06341894 - Efficacy and Safety of Dalpiciclib With Endocrine Therapy as Adjuvant Treatment in HR+/ HER2- Early Breast Cancer Phase 2
Not yet recruiting NCT06404736 - QL1706 Plus Chemotherapy as Neoadjuvant Therapy in Early High-Risk TNBC Breast Cancer Phase 2
Not yet recruiting NCT06404463 - QL1706 Plus Chemotherapy as Neoadjuvant Therapy in Early High-Risk ER+/HER2- Breast Cancer Phase 2
Not yet recruiting NCT06435104 - Aromatherapy in the Treatment of Early Breast Cancer Phase 2
Recruiting NCT03520894 - Radiotherapy in Preoperative Setting With CyberKnife for Breast Cancer N/A
Completed NCT03786198 - Activity Program During Aromatase Inhibitor Therapy N/A
Completed NCT01613352 - Feasibility of Ambulatory Surgery for Early Breast Cancer N/A
Completed NCT02738970 - A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC) Phase 1
Recruiting NCT01792726 - A Comparison of Intra-operative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer. N/A
Completed NCT00323479 - Arthralgia During Anastrozole Therapy for Breast Cancer Phase 4
Completed NCT03493854 - A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Participants With HER2-Positive Early Breast Cancer Phase 3
Recruiting NCT04291378 - The DBCG Proton Trial: Photon Versus Proton Radiation Therapy for Early Breast Cancer N/A