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

Phase 3Active Not RecruitingNCT03423199

National Cancer Center, Japan180 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

180

Conditions

Breast Neoplasms

Interventions

PalbociclibDRUG

Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

PlaceboDRUG

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

TamoxifenDRUG

Tamoxifen, 20mg, orally once daily (continuously)

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (23)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Outcomes

Primary Outcomes

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.

Time frame: Baseline up to 3.5 years

Secondary Outcomes

Overall Survival (OS)

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

Time frame: From the randomization of the last patient up to 3 years

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.

Time frame: From the randomization of the last patient up to 3 years

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.

Time frame: Baseline up to 3.5 years

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.

Time frame: Baseline up to 3.5 years

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.

Time frame: Baseline up to 3.5 years

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Hyogo Cancer Center

Akashi, Hyōgo, Japan

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Kindai University Hospital

Ōsaka-sayama, Osaka, Japan

Toranomon Hospital

Minato-Ku, Tokyo, Japan

Chiba Cancer Center

Chiba, Japan

Kyusyu Cancer Center

Fukuoka, Japan

...and 13 more locations

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.

Time frame: Baseline up to 3.5 years

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.

Time frame: Baseline up to 3.5 years

Trough plasma concentrations of palbociclib

Ctrough for palbociclib

Time frame: Cycle 1/Day 15 and Cycle 2/Day 15

Trough plasma concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen

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

Time frame: Cycle 2/Day 15 and Cycle 3/Day 15

Treatment-Emergent Adverse Events

Time frame: From the first dose of the investigational product until 28 days after the last dose of study drugs