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

Breast Neoplasms Clinical Trial

— PATHWAY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03423199
• Other study ID #: NCCH1607
• Secondary ID: WI217662
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 9, 2018
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: National Cancer Center, Japan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 180
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Palbociclib
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
• Placebo
Placebo, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
• Tamoxifen
Tamoxifen, 20mg, orally once daily (continuously)
• Goserelin
For pre/perimenopausal patients only: Goserelin, 3.6 mg, subcutaneously every 4 weeks; or 10.8 mg, subcutaneously every 12 weeks

Locations

Country	Name	City	State
Japan	Hyogo Cancer Center	Akashi	Hyogo
Japan	Chiba Cancer Center	Chiba
Japan	Kyusyu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Toranomon Hospital	Minato-Ku	Tokyo
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Kindai University Hospital	Osaka-sayama	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	National Cancer Center Hospital	Tokyo
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Soeul
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Hospital	Singapore
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Sun Yat-Sen Cancer Center	Taipei
Taiwan	Taipei Vetarans General Hospital	Taipei

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Center, Japan	Korean Cancer Study Group, Pfizer

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	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.	Baseline up to 3.5 years
Secondary	Overall Survival (OS)	The time from date of randomization to date of death due to any cause.	From the randomization of the last patient up to 3 years
Secondary	Survival Probabilities at 1 year, 2 year, and 3 year	The probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate.	From the randomization of the last patient up to 3 years
Secondary	Objective Response (OR)	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.	Baseline up to 3.5 years
Secondary	Duration of Response (DR)	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.	Baseline up to 3.5 years
Secondary	Clinical Benefit Response (CBR)	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.	Baseline up to 3.5 years
Secondary	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	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.	Baseline up to 3.5 years
Secondary	Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores	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.	Baseline up to 3.5 years
Secondary	Trough plasma concentrations of palbociclib	Ctrough for palbociclib	Cycle 1/Day 15 and Cycle 2/Day 15
Secondary	Trough plasma concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen	Ctrough for tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen	Cycle 2/Day 15 and Cycle 3/Day 15
Secondary	Treatment-Emergent Adverse Events		From the first dose of the investigational product until 28 days after the last dose of study drugs