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

NCT ID: NCT03969121

Last Updated: 2023-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-16
• Study Completion Date: 2021-12-23

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.

Conditions

Breast Cancer Female; Hormone Receptor Positive Malignant Neoplasm of Breast

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo + Endocrine therapy

Endocrine therapy for 16 weeks plus placebo

Group Type: ACTIVE_COMPARATOR

Endocrine therapy

Intervention Type: DRUG

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.

Palbociclib + Endocrine therapy

Endocrine therapy for 16 weeks plus Palbociclib

Group Type: ACTIVE_COMPARATOR

Palbociclib

Intervention Type: DRUG

Palbociclib will be administered orally once a day for 21 days every 28-day cycle followed by 7 days off treatment

Endocrine therapy

Intervention Type: DRUG

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.

Interventions

Palbociclib

Palbociclib will be administered orally once a day for 21 days every 28-day cycle followed by 7 days off treatment

Intervention Type: 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.

Intervention Type: DRUG

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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Kyoto Breast Cancer Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Masakazu Toi, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Kyoto University, Professor of Breast Surgery Department

Louis WC Chow, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Organisation for Oncology and Translational Research (OOTR)

Takayuki Ueno, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute Hospital of JFCR, Department Director, Breast Surgical Oncology Department

Locations

Monash Health

Clayton, , Australia

Peter MacCallum Cancer Centre

Melbourne, , Australia

UNIMED Medical Institute

Hong Kong, , Hong Kong

Amagasaki General Medical Center

Amagasaki, Hyōgo, Japan

University of Tsukuba Hospital

Tsukuba, Ibaraki, Japan

Kyushu Cancer Center

Fukuoka, , Japan

Sagara Hospital

Kagoshima, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

Kyoto University Hospital

Kyoto, , Japan

Aichi Cancer Center

Nagoya, , Japan

Tazuke Kofukai, Medical Research Institute, Kitano Hospital

Osaka, , Japan

Saitama Cancer Center

Saitama, , Japan

Toranomon Hospital

Tokyo, , Japan

Tokyo Metropolitan Komagome Hospital

Tokyo, , Japan

Cancer Institute Hospital Of JFCR

Tokyo, , Japan

Kyorin University Hospital

Tokyo, , Japan

Kanagawa Cancer Center

Yokohama, , Japan

National Cancer Center, Korea

Gyeonggi-do, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Korea Cancer Center Hospital

Seoul, , South Korea

Seoul National University College of Medicine

Seoul, , South Korea

Changhua Christian Hospital

Changhua, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Countries

Australia; Hong Kong; Japan; South Korea; Taiwan

References

Ueno T, Chow LWC, Han W, Huang CS, Mann GB, Morita S, Haga H, Fakhrejahani E, Kobayashi T, Bando H, Inoue K, Tokiwa M, Suwa H, Aruga T, Minamiguchi S, Yamada Y, Tanabe Y, Takada M, Yamashita T, Iwata H, Chung CF, Takahara S, Tokunaga E, Imoto S, Lee ES, Sagara Y, Kim JH, DeBoer RH, Kim HA, Lai HW, Hou MF, White M, Umeyama Y, Toi M. Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer. Endocr Relat Cancer. 2025 Sep 11;32(9):e240353. doi: 10.1530/ERC-24-0353. Print 2025 Sep 1.

Reference Type: DERIVED

PMID: 40888443 (View on PubMed)

Other Identifiers

OOTR-N016/KBCRN-B-003/HT-PAB

Identifier Type: -

Identifier Source: org_study_id