Back to resultsPAlbociclib Plus Tamoxifen for the Treatment of Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Women - Asian studY (PATHWAY)
Primary Purpose
Breast Neoplasms
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Palbociclib
Placebo
Tamoxifen
Goserelin
Sponsored by
About this trial
This is an interventional treatment trial for Breast Neoplasms focused on measuring breast Cancer, palbociclib (PD-0332991), tamoxifen, goserelin, any menopausal status, hormone receptor positive, HER2 negative, locally advanced, metastatic
Eligibility Criteria
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
Sites / Locations
- Aichi Cancer Center Hospital
- National Cancer Center Hospital East
- National Hospital Organization Shikoku Cancer Center
- National Hospital Organization Hokkaido Cancer Center
- Hyogo Cancer Center
- Kanagawa Cancer Center
- Kindai University Hospital
- Toranomon Hospital
- Chiba Cancer Center
- Kyusyu Cancer Center
- National Hospital Organization Osaka National Hospital
- National Cancer Center Hospital
- National Cancer Center
- Ajou University Hospital
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- Asan Medical Center
- Severance Hospital, Yonsei University Health System
- National University Hospital
- National Cancer Centre Singapore
- National Taiwan University Hospital
- Taipei Vetarans General Hospital
- Sun Yat-Sen Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Palbociclib + Tamoxifen ± Goserelin
Placebo + Tamoxifen ± Goserelin
Arm Description
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 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)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Overall Survival (OS)
The time from date of randomization to date of death due to any cause.
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.
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.
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.
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.
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.
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.
Trough plasma concentrations of palbociclib
Ctrough for palbociclib
Trough plasma concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen
Ctrough for tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen
Treatment-Emergent Adverse Events
Full Information
NCT ID
NCT03423199
First Posted
January 9, 2018
Last Updated
March 21, 2023
Sponsor
National Cancer Center, Japan
Collaborators
Pfizer, Korean Cancer Study Group
1. Study Identification
Unique Protocol Identification Number
NCT03423199
Brief Title
PAlbociclib Plus Tamoxifen for the Treatment of Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Women - Asian studY
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 9, 2018 (Actual)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
April 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Center, Japan
Collaborators
Pfizer, Korean Cancer Study Group
4. Oversight
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
Data Monitoring Committee
Yes
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms
Keywords
breast Cancer, palbociclib (PD-0332991), tamoxifen, goserelin, any menopausal status, hormone receptor positive, HER2 negative, locally advanced, metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
180 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Palbociclib + Tamoxifen ± Goserelin
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo + Tamoxifen ± Goserelin
Arm Type
Active Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Other Intervention Name(s)
PD-0332991
Intervention Description
Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
Intervention Type
Drug
Intervention Name(s)
Tamoxifen
Intervention Description
Tamoxifen, 20mg, orally once daily (continuously)
Intervention Type
Drug
Intervention Name(s)
Goserelin
Intervention Description
For pre/perimenopausal patients only: Goserelin, 3.6 mg, subcutaneously every 4 weeks; or 10.8 mg, subcutaneously every 12 weeks
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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 Outcome Measure Information:
Title
Overall Survival (OS)
Description
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
Title
Survival Probabilities at 1 year, 2 year, and 3 year
Description
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
Title
Objective Response (OR)
Description
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
Title
Duration of Response (DR)
Description
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
Title
Clinical Benefit Response (CBR)
Description
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
Title
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
Description
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
Title
Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores
Description
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
Title
Trough plasma concentrations of palbociclib
Description
Ctrough for palbociclib
Time Frame
Cycle 1/Day 15 and Cycle 2/Day 15
Title
Trough plasma concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen
Description
Ctrough for tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and endoxifen
Time Frame
Cycle 2/Day 15 and Cycle 3/Day 15
Title
Treatment-Emergent Adverse Events
Time Frame
From the first dose of the investigational product until 28 days after the last dose of study drugs
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kan Yonemori, MD, PhD
Organizational Affiliation
Department of Breast and Medical Oncology, National Cancer Center Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Aichi Cancer Center Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
2778577
Country
Japan
Facility Name
National Hospital Organization Shikoku Cancer Center
City
Matsuyama
State/Province
Ehime
ZIP/Postal Code
7910280
Country
Japan
Facility Name
National Hospital Organization Hokkaido Cancer Center
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
0030804
Country
Japan
Facility Name
Hyogo Cancer Center
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
6738558
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
2418515
Country
Japan
Facility Name
Kindai University Hospital
City
Ōsaka-sayama
State/Province
Osaka
ZIP/Postal Code
5898511
Country
Japan
Facility Name
Toranomon Hospital
City
Minato-Ku
State/Province
Tokyo
ZIP/Postal Code
1058470
Country
Japan
Facility Name
Chiba Cancer Center
City
Chiba
ZIP/Postal Code
2608717
Country
Japan
Facility Name
Kyusyu Cancer Center
City
Fukuoka
ZIP/Postal Code
8111395
Country
Japan
Facility Name
National Hospital Organization Osaka National Hospital
City
Osaka
ZIP/Postal Code
5400006
Country
Japan
Facility Name
National Cancer Center Hospital
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
National Cancer Center
City
Gyeonggi-do
ZIP/Postal Code
10408
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Gyeonggi-do
ZIP/Postal Code
16499
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Gyeonggi-do
ZIP/Postal Code
463-707
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Soeul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119882
Country
Singapore
Facility Name
National Cancer Centre Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Taipei Vetarans General Hospital
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Sun Yat-Sen Cancer Center
City
Taipei
ZIP/Postal Code
11259
Country
Taiwan
12. IPD Sharing Statement
Learn more about this trial
PAlbociclib Plus Tamoxifen for the Treatment of Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Women - Asian studY
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