A Study of Palbociclib With Exemestane Plus GnRH Versus Capecitabine in Premenopausal Women With HR+ MBC

• ClinicalTrials.gov Identifier: NCT02592746
• Recruitment Status: Unknown
• First Posted: October 30, 2015
• Last Update Posted: April 8, 2019
• Sponsor: Samsung Medical Center
• Information provided by (Responsible Party): Yeon Hee Park, Samsung Medical Center

Tracking Information

• First Submitted Date: October 29, 2015
• First Posted Date: October 30, 2015
• Last Update Posted Date: April 8, 2019
• Study Start Date: June 2016
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 29, 2015): Progression free survival (PFS) in patients with metastatic breast cancer who received palbociclib plus exemestane with goserelin versus capecitabine [ Time Frame: 1year ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Breast Cancer

Intervention

• Drug: Palbociclib
  Palbociclib 125mg, orally once daily on D1 to D21 followed by 7days off
  Other Name: PD-0332991
• Drug: Exemestane
  Exemestane 25mg, orally once daily
  Other Name: FCE-24304
• Drug: Leuprolide Acetate
  Leuprolide Acetate 3.75mg SC q 4weeks
  Other Name: GnRH agonist
• Drug: Capecitabine
  Capecitabine 1,250mg/m2 bid orally form day1 to day 14 q 3weeks
  Other Name: Xeloda

Study Arms

• Experimental: Palbociclib + Exemestane + GnRH agonist
  Interventions:

  • Drug: Palbociclib
  • Drug: Exemestane
  • Drug: Leuprolide Acetate
• Active Comparator: Capecitabine
  Intervention: Drug: Capecitabine

• Publications *: 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: January 15, 2018): 182
• Original Estimated Enrollment (submitted: October 29, 2015): 122
• Estimated Study Completion Date: June 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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
2. Age > 19 years
3. ECOG performance status 0 - 2
4. 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

5. 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

6. 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 .
7. Urine or serum HCG test must be negative.
8. Adequate bone marrow function (≥ ANC 1,500/ul, ≥ platelet 100,000/ul, ≥ Hemoglobin 9.0 g/dl)
9. Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 50 ml/min)
10. Adequate liver function (≤ serum bilirubin 1.5 mg/dl, ≤ AST/ALT x 3 upper normal limit)
11. Patients who were already established on bisphosphonate therapy may continue on bisphosphonates.
12. Patients agreed to use effective contraception or not of childbearing potential
13. Written informed consent
14. Consent to biomarker analysis.

Exclusion Criteria:

1. Postmenopausal women
2. Serious uncontrolled intercurrent infections
3. Serious intercurrent medical or psychiatric illness, including active cardiac disease
4. Pregnancy or breast feeding
5. 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)
6. Patients has received previous endocrine treatments such as, aromatase inhibitor, exemestane in the metastatic setting
7. Patients has received previous treatment with CDK 4/6 inhibitors, mTOR inhibitors, PIK3CA inhibitors or capecitabine
8. No symptomatic visceral metastasis
9. Known brain metastases unless treated and stable
10. Clinically significant uncontrolled conditions including, known active hepatitis B or hepatitis C.
11. QTc interval > 480 msec, family or personal history of long or short QT syndrome, or known history of QTc prolongation or Torsade de Pointes.
12. Known positive testing for human immunodeficiency virus or acquired immune deficiency syndrome.
13. Unable to swallow and retain oral medication.
14. Treatment radiotherapy within 4 weeks of the study
15. Use of any investigational drug within 4 weeks of the study
16. Treatment with chemotherapy within 3 weeks or hormone therapy within 2 weeks of the study

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT02592746
• Other Study ID Numbers: 2015-08-042
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yeon Hee Park, Samsung Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Samsung Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Samsung Medical Center
• Verification Date: April 2019