Clinical Trials /

Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer

NCT03969121

Description:

The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the efficacy of palbociclib in combination with Endocrine therapy over Endocrine therapy alone measured by PEPI and EndoPredict™ EPclin Score in women with operable HR+, HER2 negative breast cancer . The Clinical Response Rate, drop in Ki67 index ≤ 2.7% and Breast conserving rate will be compared between two arms.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer
  • Official Title: A Phase III Randomized, Double-Blind, Neoadjuvant Study of Hormonal Therapy Plus Palbociclib Versus Hormonal Therapy Plus Placebo in Women With Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: OOTR-N016/KBCRN-B-003/HT-PAB
  • NCT ID: NCT03969121

Conditions

  • Breast Cancer Female
  • Hormone Receptor Positive Malignant Neoplasm of Breast

Interventions

DrugSynonymsArms
PalbociclibPalbociclib + Endocrine therapy
Endocrine therapyPlacebo + Endocrine therapy

Purpose

The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the efficacy of palbociclib in combination with Endocrine therapy over Endocrine therapy alone measured by PEPI and EndoPredict™ EPclin Score in women with operable HR+, HER2 negative breast cancer . The Clinical Response Rate, drop in Ki67 index ≤ 2.7% and Breast conserving rate will be compared between two arms.

Trial Arms

NameTypeDescriptionInterventions
Placebo + Endocrine therapyActive ComparatorEndocrine therapy for 16 weeks plus placebo
  • Endocrine therapy
Palbociclib + Endocrine therapyActive ComparatorEndocrine therapy for 16 weeks plus Palbociclib
  • Palbociclib
  • Endocrine therapy

Eligibility Criteria

        Inclusion Criteria:

        1. Pre/peri- or post-menopausal women 18 years and older (or local legal age, whichever is
        higher) 2. Primary tumor greater than 2 cm in diameter 3. Histologically proven invasive
        breast cancer 4. Positive hormone receptor (ER and/or PgR ≥ Allred 3) 5. Negative HER-2
        receptor 6. Ki67 index equal to or greater than 14% (Ki67 ≥ 14%) by central assessment 7.
        Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1 or Karnofsky
        performance status ≥ 70% 8. No previous history of radiotherapy or systemic therapy
        including chemotherapy and hormone therapy for breast cancer 9. Laboratory values must be
        as follows: Absolute neutrophil count: ≥ 1,500/mm3 Platelets: ≥ 100,000/mm3 Hemoglobin: ≥ 9
        g/dL Bilirubin: ≤ 1.5 × upper limits of normal (ULN) Serum Creatinine: ≤ 1.5 × ULN Alkaline
        phosphatase: ≤ 2 × ULN AST and ALT: ≤ 2 × ULN Cardiac function: Normal finding of
        Electrocardiogram (ECG) QTc ≤ 480 msec (based on the mean value of the triplicate ECGs).

        10. Able to give written informed consent form 11. Willingness and ability to comply with
        scheduled visits, treatment plan, laboratory tests, and other study procedures

        Exclusion Criteria:

          1. Male

          2. Locally advanced breast cancer (T3N1 or Any T4 or Any N2, N3), or distant me-tastasis

          3. Multifocal or multicentric breast cancer

          4. Prior treatment with chemotherapy, radiotherapy and/or endocrine therapy

          5. Previous use of SERMs such as raloxifene.

          6. Prior therapy with any CDK4/6 inhibitor or with everolimus, or any agent whose
             mechanism of action is to inhibit the PI3K-mTOR pathway.

          7. Prior history of other malignancy within 5 years of study entry, aside from basal cell
             carcinoma of the skin or carcinoma-in-situ of the uterine cervix

          8. Major surgery within 3 weeks of first study treatment

          9. Patients treated within the last 7 days prior to randomization with:

               -  Food or drugs that are known strong and moderate CYP3A4 inhibitors (e.g.,
                  amprenavir, aprepitant, atazanavir, boceprevir, casopitant, cimetidine,
                  ciprof-loxacin, clarithromycin, conivaptan, cobicistat, crizotinib, cyclosporine,
                  da-runavir, diltiazem, dronedarone, elvitegravir, erythromycin, fluconazole,
                  fosamprenavir, imatinib, indinavir, isavuconazole, istradefylline,
                  itraconazole,ketoconazole, letermovir, lopinavir, mibefradil, miconazole,
                  nefazodone, nelfinavir, nilotinib, posaconazole, ritonavir, saquinavir,
                  schisandra sphenan-thera extract, telaprevir, telithromycin, tofisopam,
                  verapamil, voriconazole, and grapefruit, grapefruit juice or any product
                  containing grapefruit);

               -  Drugs that are known strong and moderate CYP3A4 inducers (e.g., bosentan,
                  carbamazepine, efavirenz, etravirine, modafinil, phenobarbital, phenytoin,
                  ri-fampin, rifapentin, and St. John's wort);

         10. Any of the following in the previous 6 months of randomization: myocardial
             in-farction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version
             4.03 grade ≥ 2, atrial fibrillation of any grade, coronary/peripheral artery bypass
             graft, symptomatic congestive heart failure, cerebrovascular accident in-cluding
             transient ischemic attack, or symptomatic pulmonary embolism

         11. Family or personal history of long or short QT syndrome, Brugada syndrome or known
             history of QTc prolongation, or Torsade de Pointes (TdP).

         12. Uncontrolled electrolyte disorders (eg, hypocalcemia, hypokalemia, hypomag-nesemia)
             that can compound the effects of a QTc-prolonging drug.

         13. Active inflammatory bowel disease or chronic diarrhea. Short bowel syndrome. Upper
             gastrointestinal surgery including gastric resection.

         14. Prior hematopoietic stem cell or bone marrow transplantation.

         15. Known abnormalities in coagulation such as bleeding diathesis, or treatment with
             anticoagulants precluding subcutaneous injections of leuprorelin or goserelin.

         16. Hepatitis B and/or hepatitis C carriers (unless with normal hepatic function)

         17. Known human immunodeficiency virus (HIV) infection

         18. Known hypersensitivity to anti-aromatase drugs, tamoxifen or any cell cycle
             in-hibitor.

         19. Patients who are pregnant or lactating. Patients of childbearing potential and/or her
             partner who are unwilling or unable to use a method of highly effective non-hormonal
             contraception throughout the study and continue for at least 21 days in patients and
             90 days in her partner after the last dose of investigational drug.

         20. Other severe acute or chronic medical or psychiatric condition, or laboratory
             ab-normality that would impart, in the judgment of the investigator, excess risk
             as-sociated with study participation or study drug administration, or which, in the
             judgment of the investigator, would make the patient inappropriate for entry into this
             study

         21. Patients who are investigational site staff members or relatives of those site staff
             OOTR-N016/KBCRN-B-003/HT-PAB Protocol (version 1.2 dated Oct 11, 2018) 24 members or
             patients who are the sponsor employees directly involved in the con-duct of the trial.
             22. Participation in other studies involving investigational drug (s) (Phases 1-4)
             within 2 weeks before randomization and/or during participation in the active
             treatment phase of the trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pre-operative Endocrine Prognostic Index (PEPI Score)
Time Frame:4 months
Safety Issue:
Description:The PEPI score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, ( including Ki67 expression in the surgical specimen, pathologic tumor size, lymph node status, and estrogen receptor (ER) level). The PEPI score is the sum of each component score and shows the risk points for relapse-free survival. PEPI=0 means low risk. PEPI= 1 to 3 means intermediate risk . PEPI more than 4 means high risk.

Secondary Outcome Measures

Measure:Clinical Response Rate
Time Frame:4 months
Safety Issue:
Description:Observing any reduction in largest tumor diameter on clinical breast examination and ultrasound imaging of breast and axilla after 4 months
Measure:Ki67 change
Time Frame:4 months
Safety Issue:
Description:Drop in Ki67 index to less than or equal to 2.7%
Measure:pathological response rate
Time Frame:4 months
Safety Issue:
Description:Evaluating the rate of pathological Complete Response based on assessment of surgical specimen
Measure:Breast conserving rate
Time Frame:4 months
Safety Issue:
Description:Calculating the rate of breast conserving surgery based on the number of each surgery type
Measure:Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment as Assessed by CTCAE v4.03
Time Frame:4 months
Safety Issue:
Description:Type, incidence, severity (as graded by National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03), seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Kyoto Breast Cancer Research Network

Trial Keywords

  • Palbociclib
  • Breast Cancer
  • PEPI

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