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

Phase 3

Active, not recruiting

• Conditions: Breast Neoplasms
• Interventions: Drug: Placebo; Drug: Palbociclib; Drug: Tamoxifen; Drug: Goserelin

• Registration Number: NCT03423199
• Lead Sponsor: National Cancer Center, Japan

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-09
• Study First Submitted QC: 2018-02-03
• Study First Posted: 2018-02-06
• Study Start: 2018-02-09
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-22
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 180

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Palbociclib + Tamoxifen ± Goserelin	Tamoxifen	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)
Placebo + Tamoxifen ± Goserelin	Placebo	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)
Palbociclib + Tamoxifen ± Goserelin	Palbociclib	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)
Palbociclib + Tamoxifen ± Goserelin	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)
Placebo + Tamoxifen ± Goserelin	Tamoxifen	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)
Placebo + Tamoxifen ± Goserelin	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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
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.
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.
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.
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.
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.
Trough plasma concentrations of palbociclib	Cycle 1/Day 15 and Cycle 2/Day 15	Ctrough for palbociclib
Treatment-Emergent Adverse Events	From the first dose of the investigational product until 28 days after the last dose of study drugs

Trial Locations

Locations (23)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Sun Yat-Sen Cancer Center; 🇨🇳 Taipei, Taiwan

Chiba Cancer Center; 🇯🇵 Chiba, Japan

National Cancer Center Hospital; 🇯🇵 Tokyo, Japan

Kanagawa Cancer Center; 🇯🇵 Yokohama, Kanagawa, Japan

Aichi Cancer Center Hospital; 🇯🇵 Nagoya, Aichi, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Chiba, Japan

National Hospital Organization Hokkaido Cancer Center; 🇯🇵 Sapporo, Hokkaido, Japan

National Hospital Organization Shikoku Cancer Center; 🇯🇵 Matsuyama, Ehime, Japan

Toranomon Hospital; 🇯🇵 Minato-Ku, Tokyo, Japan

Hyogo Cancer Center; 🇯🇵 Akashi, Hyogo, Japan

Kindai University Hospital; 🇯🇵 Ōsaka-sayama, Osaka, Japan

National Hospital Organization Osaka National Hospital; 🇯🇵 Osaka, Japan

Kyusyu Cancer Center; 🇯🇵 Fukuoka, Japan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

National Cancer Center; 🇰🇷 Gyeonggi-do, Korea, Republic of

Ajou University Hospital; 🇰🇷 Gyeonggi-do, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Gyeonggi-do, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

National University Hospital; 🇸🇬 Singapore, Singapore

Severance Hospital, Yonsei University Health System; 🇰🇷 Soeul, Korea, Republic of

National Cancer Centre Singapore; 🇸🇬 Singapore, Singapore

Taipei Vetarans General Hospital; 🇨🇳 Taipei, Taiwan