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PATHWAY: PAlbociclib Plus Tamoxifen for the Treatment of Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Women - Asian studY

Sponsor
National Cancer Center, Japan (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03423199
Collaborator
Pfizer (Industry), Korean Cancer Study Group (Other)
180
Enrollment
23
Locations
2
Arms
52.7
Anticipated Duration (Months)
7.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is conducted to evaluate the benefit of adding palbociclib in hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer patients, regardless of menopausal status, treated with tamoxifen (with or without goserelin) versus tamoxifen alone (with or without goserelin).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
180 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Asian, International, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tamoxifen With or Without Palbociclib ± Goserelin in Women With Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer
Actual Study Start Date :
Feb 9, 2018
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Palbociclib + Tamoxifen ± Goserelin

Palbociclib 125 mg/day, orally once daily on Day 1 to Day 21 followed by 7 days off treatment for each 28 day cycle, plus tamoxifen 20 mg orally once daily (continuously)

Drug: Palbociclib
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
Other Names:
  • PD-0332991

    • Drug: Tamoxifen
    Tamoxifen, 20mg, orally once daily (continuously)

    Drug: Goserelin
    For pre/perimenopausal patients only: Goserelin, 3.6 mg, subcutaneously every 4 weeks; or 10.8 mg, subcutaneously every 12 weeks
    Active Comparator: Placebo + Tamoxifen ± Goserelin

    Placebo orally once daily on Day 1 to Day 21 followed by 7 days off treatment for each 28 day cycle, plus tamoxifen 20 mg orally once daily (continuously)

    Drug: Placebo
    Placebo, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

    Drug: Tamoxifen
    Tamoxifen, 20mg, orally once daily (continuously)

    Drug: Goserelin
    For pre/perimenopausal patients only: Goserelin, 3.6 mg, subcutaneously every 4 weeks; or 10.8 mg, subcutaneously every 12 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) [Baseline up to 3.5 years]

      The time from the date of randomization to the date of the first documentation of objective progression of disease (PD), clinically diagnosed symptomatic deterioration, or death due to any cause in the absence of documented PD, whichever occurs first.

    Secondary Outcome Measures

    1. Overall Survival (OS) [From the randomization of the last patient up to 3 years]

      The time from date of randomization to date of death due to any cause.

    2. Survival Probabilities at 1 year, 2 year, and 3 year [From the randomization of the last patient up to 3 years]

      The probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate.

    3. Objective Response (OR) [Baseline up to 3.5 years]

      Complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST) ver.1.1 recorded from randomization until disease progression or death due to any cause.

    4. Duration of Response (DR) [Baseline up to 3.5 years]

      The time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.

    5. Clinical Benefit Response (CBR) [Baseline up to 3.5 years]

      CR or PR or SD >=24 weeks according to the RECIST version 1.1 recorded in the time period between randomization and disease progression or death of any cause.

    6. Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores [Baseline up to 3.5 years]

      The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.

    7. Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores [Baseline up to 3.5 years]

      The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning.

    8. Trough plasma concentrations of palbociclib [Cycle 1/Day 15 and Cycle 2/Day 15]

      Ctrough for palbociclib

    9. Trough plasma concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen [Cycle 2/Day 15 and Cycle 3/Day 15]

      Ctrough for tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen

    10. Treatment-Emergent Adverse Events [From the first dose of the investigational product until 28 days after the last dose of study drugs]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Women 18 years of age or older with histologically or cytologically proven locally advanced or metastatic breast cancer, not amenable to resection or radiation therapy with curative intent

    • Documented diagnosis of HR+/HER2- breast cancer

    • Any menopausal status

    • Previously untreated with any endocrine therapy for their HR+/HER2- advanced breast cancer; or progressed while on or within 3 month from prior endocrine therapy other than tamoxifen for advanced breast cancer. If patients have adjuvant endocrine therapy, they must satisfy as follows: progressed 12 months or more since prior adjuvant endocrine therapy with tamoxifen; or progressed during or after adjuvant endocrine therapy with an aromatase inhibitor.

    • Measurable disease or non-measurable disease as defined by RECIST ver.1.1

    • Eastern Cooperative Oncology Group (ECOG) PS 0-1

    • Adequate organ and marrow function, resolution of all toxic effects of prior therapy or surgical procedures

    Exclusion Criteria:

    • Prior treatment with any CDK inhibitor, tamoxifen, everolimus, or agent that inhibits the PI3K-mTOR pathway

    • Patients with extensive advanced/metastatic, symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases

    • Use of strong or moderate CYP3A4 and/or CYP2D6 inhibitors or inducers

    • Major surgery or any anti-cancer therapy within 2 weeks of randomization

    • Prior stem cell or bone marrow transplantation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aichi Cancer Center Hospital Nagoya Aichi Japan 464-8681
    2 National Cancer Center Hospital East Kashiwa Chiba Japan 2778577
    3 National Hospital Organization Shikoku Cancer Center Matsuyama Ehime Japan 7910280
    4 National Hospital Organization Hokkaido Cancer Center Sapporo Hokkaido Japan 0030804
    5 Hyogo Cancer Center Akashi Hyogo Japan 6738558
    6 Kanagawa Cancer Center Yokohama Kanagawa Japan 2418515
    7 Kindai University Hospital Ōsaka-sayama Osaka Japan 5898511
    8 Toranomon Hospital Minato-Ku Tokyo Japan 1058470
    9 Chiba Cancer Center Chiba Japan 2608717
    10 Kyusyu Cancer Center Fukuoka Japan 8111395
    11 National Hospital Organization Osaka National Hospital Osaka Japan 5400006
    12 National Cancer Center Hospital Tokyo Japan 104-0045
    13 National Cancer Center Gyeonggi-do Korea, Republic of 10408
    14 Ajou University Hospital Gyeonggi-do Korea, Republic of 16499
    15 Seoul National University Bundang Hospital Gyeonggi-do Korea, Republic of 463-707
    16 Seoul National University Hospital Seoul Korea, Republic of 03080
    17 Asan Medical Center Seoul Korea, Republic of 05505
    18 Severance Hospital, Yonsei University Health System Soeul Korea, Republic of 03722
    19 National University Hospital Singapore Singapore 119882
    20 National Cancer Centre Singapore Singapore Singapore 169610
    21 National Taiwan University Hospital Taipei Taiwan 10048
    22 Taipei Vetarans General Hospital Taipei Taiwan 11217
    23 Sun Yat-Sen Cancer Center Taipei Taiwan 11259

    Sponsors and Collaborators

    • National Cancer Center, Japan
    • Pfizer
    • Korean Cancer Study Group

    Investigators

    • Study Chair: Kan Yonemori, MD, PhD, Department of Breast and Medical Oncology, National Cancer Center Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Center, Japan
    ClinicalTrials.gov Identifier:
    NCT03423199
    Other Study ID Numbers:
    • NCCH1607
    • WI217662
    First Posted:
    Feb 6, 2018
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022
    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
    Keywords provided by National Cancer Center, Japan
    breast Cancer
    palbociclib (PD-0332991)
    tamoxifen
    goserelin
    any menopausal status
    hormone receptor positive
    HER2 negative
    locally advanced
    metastatic
    Additional relevant MeSH terms:
    Breast Neoplasms
    Tamoxifen
    Goserelin
    Palbociclib

    Study Results

    No Results Posted as of Apr 6, 2022