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

NCT03969121

Last updated date
Study Location
Monash Health
Clayton, Victoria, 3168, Australia
Contact
0755857861

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Breast Cancer Female, Hormone Receptor Positive Malignant Neoplasm of Breast
Sex
Female
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Pre/peri- or post-menopausal women 18 years and older (or local legal age, whichever is higher)

2. Primary tumor greater than 15 mm in diameter

3. Histologically proven invasive breast cancer

4. Positive hormone receptor (ER and/or PgR ≥1% in proportion of positive staining score)

5. Negative HER-2 receptor (based on 2018 ASCO/CAP Guideline)

6. Ki67 index equal to or greater than 14% (Ki67 ≥ 14%) by central assessment using actual or virtual slides

7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Male


2. Locally advanced breast cancer ( Any T4 or Any N2, N3), or distant metastasis


3. Multicentric breast cancer (Note: Multifocal breast cancer,located in one quadrant/are
is eligible)


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 (Patients with HBsAg+ or HBV-DNA+ who need
antiviral treatment during any anti-cancer therapy based on guidelines are excluded
even if the patient's hepatic function is normal. Patients with HCVAb+, whose HCV-RNA
is positive (+) are excluded.)


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 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 until a visit at 4 weeks (+7 days) after
operation.

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Breast Cancer Female, Hormone Receptor Positive Malignant Neoplasm of BreastNeoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer
NCT03969121
  1. Clayton, Victoria
  2. Melbourne,
  3. Hong Kong,
  4. Amagasaki, Hyogo
  5. Tsukuba, Ibaraki
  6. Fukuoka,
  7. Kagoshima,
  8. Kobe,
  9. Kyoto,
  10. Nagoya,
  11. Osaka,
  12. Saitama,
  13. Tokyo,
  14. Tokyo,
  15. Tokyo,
  16. Tokyo,
  17. Yokohama,
  18. Gyeonggi-do,
  19. Seongnam,
  20. Seoul,
  21. Seoul,
  22. Seoul,
  23. Suwon,
  24. Changhua,
  25. Kaohsiung,
  26. Taipei,
  27. Taipei,
Female
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Neoadjuvant Hormonal Therapy Plus Palbociclib in Operable, Hormone Sensitive and HER2-Negative Primary Breast Cancer
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer Female
  • Hormone Receptor Positive Malignant Neoplasm of Breast
Intervention  ICMJE
  • Drug: Palbociclib
    Palbociclib will be administered orally once a day for 21 days every 28-day cycle followed by 7 days off treatment
  • Drug: Endocrine therapy
    Pre- and peri-menopausal women will be receiving Ovarian Function Suppression (OFS) by either leuprorelin subcutaneous 3.75 mg q28days or goserelin subcutaneous 3.6 mg q28days plus tamoxifen 20 mg QD in 28-day cycles. Post-menopausal women will receive letrozole 2.5 mg QD in 28-day cycles.
Study Arms  ICMJE
  • Active Comparator: Placebo + Endocrine therapy
    Endocrine therapy for 16 weeks plus placebo
    Intervention: Drug: Endocrine therapy
  • Active Comparator: Palbociclib + Endocrine therapy
    Endocrine therapy for 16 weeks plus Palbociclib
    Interventions:
    • Drug: Palbociclib
    • Drug: Endocrine therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2021
Estimated Primary Completion Date December 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 15 mm in diameter
  3. Histologically proven invasive breast cancer
  4. Positive hormone receptor (ER and/or PgR ?1% in proportion of positive staining score)
  5. Negative HER-2 receptor (based on 2018 ASCO/CAP Guideline)
  6. Ki67 index equal to or greater than 14% (Ki67 ? 14%) by central assessment using actual or virtual slides
  7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) ? 1
  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 ( Any T4 or Any N2, N3), or distant metastasis
  3. Multicentric breast cancer (Note: Multifocal breast cancer,located in one quadrant/are is eligible)
  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 (Patients with HBsAg+ or HBV-DNA+ who need antiviral treatment during any anti-cancer therapy based on guidelines are excluded even if the patient's hepatic function is normal. Patients with HCVAb+, whose HCV-RNA is positive (+) are excluded.)
  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 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 until a visit at 4 weeks (+7 days) after operation.
Sex/Gender  ICMJE
Sexes Eligible for Study:Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Elham Fakhrejahani, MD,PhD0755857861[email protected]
Listed Location Countries  ICMJE Australia,   Hong Kong,   Japan,   Korea, Republic of,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03969121
Other Study ID Numbers  ICMJE OOTR-N016/KBCRN-B-003/HT-PAB
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD:Undecided
Responsible Party Kyoto Breast Cancer Research Network
Study Sponsor  ICMJE Kyoto Breast Cancer Research Network
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Masakazu Toi, MD,PhDKyoto University, Professor of Breast Surgery Department
Principal Investigator:Louis WC Chow, MD,PhDOrganisation for Oncology and Translational Research (OOTR)
Principal Investigator:Takayuki Ueno, MD,PhDCancer Institute Hospital of JFCR, Department Director, Breast Surgical Oncology Department
PRS Account Kyoto Breast Cancer Research Network
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP