A Study of Palbociclib With Exemestane Plus GnRH Versus Capecitabine in Premenopausal Women With HR+ MBC
Primary Purpose
Metastatic Breast Cancer
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Palbociclib
Exemestane
Leuprolide Acetate
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed metastatic breast cancer with measurable or evaluable disease: Patients who have progressed on distant metastatic sites after curative surgery or have stage IV breast cancer at diagnosis
- Age > 19 years
- ECOG performance status 0 - 2
- Patient has HER2-negative breast cancer with IHC and/or FISH (or SISH, CISH) Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
Patient is premenopausal. Premenopausal status is defined as either:
A. Patient had last menstrual period within the last 12 months B. If within three months of tamoxifen (tamoxifen) taking, C. In case of chemotherapy induced amenorrhea, the serum FSH ≤40IU/l
- A. Patient who have stage IV breast cancer at diagnosis, allow disease that progressed after 1st line chemotherapy. B. Patient who have stage IV breast cancer at diagnosis, allow disease that progressed after tamoxifen or goserelin. C. In case of recur/metastatic breast cancer, allow disease that progressed after 12 month of completion of neo/adjuvant chemotherapy .
- Urine or serum HCG test must be negative.
- Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
- Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
- Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST/ALT x 3 upper normal limit)
- Patients who were already established on bisphosphonate therapy may continue on bisphosphonates.
- Patients agreed to use effective contraception or not of childbearing potential
- Written informed consent
- Consent to biomarker analysis.
Exclusion Criteria:
- Postmenopausal women
- Serious uncontrolled intercurrent infections
- Serious intercurrent medical or psychiatric illness, including active cardiac disease
- Pregnancy or breast feeding
- Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or resected thyroid papillary carcinoma or other malignancy treated at least 5 years previously with no evidence of recurrence)
- Patients has received previous endocrine treatments such as, aromatase inhibitor, exemestane in the metastatic setting
- Patients has received previous treatment with CDK 4/6 inhibitors, mTOR inhibitors, PIK3CA inhibitors or capecitabine
- No symptomatic visceral metastasis
- Known brain metastases unless treated and stable
- Clinically significant uncontrolled conditions including, known active hepatitis B or hepatitis C.
- QTc interval > 480 msec, family or personal history of long or short QT syndrome, or known history of QTc prolongation or Torsade de Pointes.
- Known positive testing for human immunodeficiency virus or acquired immune deficiency syndrome.
- Unable to swallow and retain oral medication.
- Treatment radiotherapy within 4 weeks of the study
- Use of any investigational drug within 4 weeks of the study
- Treatment with chemotherapy within 3 weeks or hormone therapy within 2 weeks of the study
Sites / Locations
- Samsung Medical Center
- Samsung Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Palbociclib + Exemestane + GnRH agonist
Capecitabine
Arm Description
Outcomes
Primary Outcome Measures
Progression free survival (PFS) in patients with metastatic breast cancer who received palbociclib plus exemestane with goserelin versus capecitabine
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02592746
Brief Title
A Study of Palbociclib With Exemestane Plus GnRH Versus Capecitabine in Premenopausal Women With HR+ MBC
Official Title
A Phase II Randomized Study of Palbociclib in Combination With Exemestane Plus GnRH Versus Capecitabine in Premenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 2016 (undefined)
Primary Completion Date
June 2021 (Anticipated)
Study Completion Date
June 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Despite recent advances for the treatment of post-menopausal hormone receptor-positive BC, in the last decade there was no major improvement of hormonal therapy specifically for premenopausal metastatic breast cancer. The median age of breast cancer is much younger, and the proportion of young breast cancer (YBC) patients (less than 40) including premenopausal women is much higher, in Asia, including Korea.
Capecitabine, the comparator in this trial, is an orally-administered fluoropyrimidine derivative and has shown high efficacy and low toxicity in metastatic breast cancer patients. Palbociclib is a CDK4/6 inhibitors, in combination with endocrine therapy showed marked advance in hormone receptor-positive MBC in the post-menopausal setting. After a median follow-up of 16.5 months, preliminary results from Part 1 of this Phase 2 trial suggest that the combination of PD-0332991 with letrozole is superior to letrozole alone, and improved objective response and disease control rates (52% vs 32% and 76% vs 47%, respectively) in patients treated with the combination. These remarkable results may contribute to have much benefit with endocrine therapy for premenopausal women. Most importantly, recent PALOMA-3 trial revealed superior results of adding palbociclib to fulvestrant (median PFS 9.2 vs 3.8 months, P<0.001).
Based on these rational backgrounds, the purpose of this phase II study is to assess the safety and the clinical anti-tumor activity of exemestane plus goserelin acetate in combination with palbociclib vs capecitabine in premenopausal hormone receptor-positive advanced breast cancer patients
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
182 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Palbociclib + Exemestane + GnRH agonist
Arm Type
Experimental
Arm Title
Capecitabine
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Other Intervention Name(s)
PD-0332991
Intervention Description
Palbociclib 125mg, orally once daily on D1 to D21 followed by 7days off
Intervention Type
Drug
Intervention Name(s)
Exemestane
Other Intervention Name(s)
FCE-24304
Intervention Description
Exemestane 25mg, orally once daily
Intervention Type
Drug
Intervention Name(s)
Leuprolide Acetate
Other Intervention Name(s)
GnRH agonist
Intervention Description
Leuprolide Acetate 3.75mg SC q 4weeks
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Capecitabine 1,250mg/m2 bid orally form day1 to day 14 q 3weeks
Primary Outcome Measure Information:
Title
Progression free survival (PFS) in patients with metastatic breast cancer who received palbociclib plus exemestane with goserelin versus capecitabine
Time Frame
1year
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed metastatic breast cancer with measurable or evaluable disease: Patients who have progressed on distant metastatic sites after curative surgery or have stage IV breast cancer at diagnosis
Age > 19 years
ECOG performance status 0 - 2
Patient has HER2-negative breast cancer with IHC and/or FISH (or SISH, CISH) Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
Patient is premenopausal. Premenopausal status is defined as either:
A. Patient had last menstrual period within the last 12 months B. If within three months of tamoxifen (tamoxifen) taking, C. In case of chemotherapy induced amenorrhea, the serum FSH ≤40IU/l
A. Patient who have stage IV breast cancer at diagnosis, allow disease that progressed after 1st line chemotherapy. B. Patient who have stage IV breast cancer at diagnosis, allow disease that progressed after tamoxifen or goserelin. C. In case of recur/metastatic breast cancer, allow disease that progressed after 12 month of completion of neo/adjuvant chemotherapy .
Urine or serum HCG test must be negative.
Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST/ALT x 3 upper normal limit)
Patients who were already established on bisphosphonate therapy may continue on bisphosphonates.
Patients agreed to use effective contraception or not of childbearing potential
Written informed consent
Consent to biomarker analysis.
Exclusion Criteria:
Postmenopausal women
Serious uncontrolled intercurrent infections
Serious intercurrent medical or psychiatric illness, including active cardiac disease
Pregnancy or breast feeding
Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or resected thyroid papillary carcinoma or other malignancy treated at least 5 years previously with no evidence of recurrence)
Patients has received previous endocrine treatments such as, aromatase inhibitor, exemestane in the metastatic setting
Patients has received previous treatment with CDK 4/6 inhibitors, mTOR inhibitors, PIK3CA inhibitors or capecitabine
No symptomatic visceral metastasis
Known brain metastases unless treated and stable
Clinically significant uncontrolled conditions including, known active hepatitis B or hepatitis C.
QTc interval > 480 msec, family or personal history of long or short QT syndrome, or known history of QTc prolongation or Torsade de Pointes.
Known positive testing for human immunodeficiency virus or acquired immune deficiency syndrome.
Unable to swallow and retain oral medication.
Treatment radiotherapy within 4 weeks of the study
Use of any investigational drug within 4 weeks of the study
Treatment with chemotherapy within 3 weeks or hormone therapy within 2 weeks of the study
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
31668850
Citation
Park YH, Kim TY, Kim GM, Kang SY, Park IH, Kim JH, Lee KE, Ahn HK, Lee MH, Kim HJ, Kim HJ, Lee JI, Koh SJ, Kim JY, Lee KH, Sohn J, Kim SB, Ahn JS, Im YH, Jung KH, Im SA; Korean Cancer Study Group (KCSG). Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1750-1759. doi: 10.1016/S1470-2045(19)30565-0. Epub 2019 Oct 24.
Results Reference
derived
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A Study of Palbociclib With Exemestane Plus GnRH Versus Capecitabine in Premenopausal Women With HR+ MBC
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