PALbociclib Endocrine Therapy Followed by Talazo vs. Talazoz-Atezo Study (Young-PALETTA)
Primary Purpose
Premenopausal HR+/HER2- Metastatic Breast Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Pabociclib, Endocrine, Talazoparib, Atezolizumab
Pabociclib, Endocrine, Talazoparib,
Sponsored by
About this trial
This is an interventional treatment trial for Premenopausal HR+/HER2- Metastatic Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed metastatic breast cancer with or without measurable disease
- Patients who have stage IV breast cancer at diagnosis (de novo) or have progressed on distant metastatic sites after curative surgery
- Confirmed germline pathogenic BRCA1 and/or 2 mutation or 35 HRD-related gene alterations
- age > 19 years
- ECOG performance status 0 - 2
- Patient has HER2-negative breast cancer with IHC and/or FISH (or SISH, CISH)
- Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
- Patient is premenopausal
- Patient with treatment history as bellows A. In patients with de novo metastatic breast cancer B. In patients with recurrent metastatic breast cancer, recurrence during or after completion or discontinuation of adjuvant endocrine therapy C. One line of prior cytotoxic chemotherapy in metastatic breast cancer is permitted.
- No possibility of pregnancy and urine or serum beta-HCG negative
- Adequate bone marrow function (≥ANC 1,500/ul, ≥platelet 100,000/ul, ≥Hemoglobin 9.0 g/dl)
- Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 650 ml/min)
- Adequate liver function (≤ serum bilirubin 2.0 mg/dl, ≤ AST/ALT x 3 upper normal limit)
- Patients who were already established on bisphosphonate therapy or denosumab may continue.
- Patient agreed to use effective contraception or not of childbearing potential.
- Written informed consent
- Patients agreed to offer tumor tissue and blood for biomarker analysis
Exclusion Criteria:
- Postmenopausal women
- Serious uncontrolled intercurrent infections within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment
- Serious intercurrent medical or psychiatric illness, including active cardiac disease
- Pregnancy or breast feeding within 5 months after the last dose of atezolizumab
- Second primary malignancy
- Patients has received previous endocrine treatments in the metastatic setting
- Patients has received previous aromatase inhibitor
- Patients has received previous treatment with CDK 4/6 inhibitors, PARP1 inhibitors, and immune check point inhibitors
- Symptomatic visceral metastases, which means lymphangitic lung metastasis and/or symptomatic hepatic metastases
- Known brain metastases, symptomatic or asymptomatic
- History of clinically significant liver disease, current alcohol abuse or known active infection
- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
- Prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computerised tomography (CT) scan
- Active tuberculosis
- Receipt of a live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment or anticipation that a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months after the last dose of atezolizumab
- Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug prior to Cycle 1 Day 1 of 1st Treatment
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1 of 1st Treatment, or anticipated requirement for systemic immunosuppressive medications during the trial
Sites / Locations
- Samsung mendical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Atezolizumab+Talazoparib
Talazoparib
Arm Description
st line treatment Palbociclib 125mg po D1-21 AI : Prescribed as per local guideline GnRH agonist: Prescribed as per local guideline nd line treatment Talazoparib 1mg po Atezolizumab 1200mg IV (3week)
st line treatment Palbociclib 125mg po D1-21 AI : Prescribed as per local guideline GnRH agonist: Prescribed as per local guideline nd line treatment - Talazoparib 1mg po
Outcomes
Primary Outcome Measures
2nd Progression free survival (PFS)
To assess measures of clinical efficacy. It is a measure of the period of survival without disease progression by Kaplan-Meier method.
Secondary Outcome Measures
Composite PFS (1st PFS + 2nd PFS)
To assess measures of clinical efficacy. It is a measure of the period of survival without disease progression by Kaplan-Meier method.
Overall survival (OS)
To assess secondary measures of clinical efficacy.
Toxicity assessment
Clinical and laboratory toxicity/symptomatology will be graded based on the NCIC CTG v5.0
Quality of Life (QoL)
The QoL will be evaluated using EQ5D
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04819243
Brief Title
PALbociclib Endocrine Therapy Followed by Talazo vs. Talazoz-Atezo Study
Acronym
Young-PALETTA
Official Title
Randomized Phase II Study of Talazoparib Versus Talazoparib Plus Atezolizumab After Palbociclib Combination Endocrine Therapy for Patients With Premenopausal HR+/HER2- Metastatic Breast Cancer Harboring HRD Scar
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 1, 2021 (Anticipated)
Primary Completion Date
September 30, 2021 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Samsung Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study is a prospective, two-arm, randomized phase II study of talazoparib versus talazoparib plus atezolizumab in ER+ premeonopausal women with metastatic breast cancer harboring HRD scar
1st line treatment: GnRH agonist + Aromatase Inhibitor(AI) + Palbociclib 28 days after the last treatment of 1st line treatment, randomization for 2nd line treatment is conducte to arm A(Talazoparib+Atezolizumab) and arm B(Talazoparib monotherapy)
Detailed Description
st line treatment
Palbociclib: A capsule will be administered once a day for 21 days and rest for 7 days (1cycle=28days)
AI treatment: D1~28 days. Take once a day. Prescribed according to local prescribe guideline.
GnRH agonist: At D1 for every cycle with 4 week (+3days) interval via subcutaneous injection.
nd line treatment
28 days after the last treatment of 1st line treatment, randomization for 2nd line treatment is conducte to arm A(Talazoparib+Atezolizumab) and arm B(Talazoparib monotherapy)
Talazoparib: Take orally once a day at the same time
Atezolizumab: 1,200mg, at D1 of each cycle. Applicable for arm A only.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Premenopausal HR+/HER2- Metastatic Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
178 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Atezolizumab+Talazoparib
Arm Type
Experimental
Arm Description
st line treatment
Palbociclib 125mg po D1-21
AI : Prescribed as per local guideline
GnRH agonist: Prescribed as per local guideline
nd line treatment
Talazoparib 1mg po
Atezolizumab 1200mg IV (3week)
Arm Title
Talazoparib
Arm Type
Experimental
Arm Description
st line treatment
Palbociclib 125mg po D1-21
AI : Prescribed as per local guideline
GnRH agonist: Prescribed as per local guideline
nd line treatment - Talazoparib 1mg po
Intervention Type
Drug
Intervention Name(s)
Pabociclib, Endocrine, Talazoparib, Atezolizumab
Intervention Description
Palbociclib 125mg
AI
GnRH agonist
Talazoparib
Atezolizumab
Intervention Type
Drug
Intervention Name(s)
Pabociclib, Endocrine, Talazoparib,
Intervention Description
Palbociclib 125mg
AI
GnRH agonist
Talazoparib
Primary Outcome Measure Information:
Title
2nd Progression free survival (PFS)
Description
To assess measures of clinical efficacy. It is a measure of the period of survival without disease progression by Kaplan-Meier method.
Time Frame
The time until the time of the first event(the progression of a recorded disease of breast cancer or death from all causes) in 2nd line treatment. Up to 72months
Secondary Outcome Measure Information:
Title
Composite PFS (1st PFS + 2nd PFS)
Description
To assess measures of clinical efficacy. It is a measure of the period of survival without disease progression by Kaplan-Meier method.
Time Frame
The time from the day 1 of first therapy to the time of first event (documented disease progression of breast cancer or death due to any cause) in 1st and 2nd line therapy. Up to 72months
Title
Overall survival (OS)
Description
To assess secondary measures of clinical efficacy.
Time Frame
Survival will be measured as the time from the randomization occurs after Progression of 1st line to the date of death. Up to 72months
Title
Toxicity assessment
Description
Clinical and laboratory toxicity/symptomatology will be graded based on the NCIC CTG v5.0
Time Frame
from the date of informed consent signature to 28 days after last drug administration
Title
Quality of Life (QoL)
Description
The QoL will be evaluated using EQ5D
Time Frame
from the date of informed consent signature to 28 days after last drug administration
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed metastatic breast cancer with or without measurable disease
Patients who have stage IV breast cancer at diagnosis (de novo) or have progressed on distant metastatic sites after curative surgery
Confirmed germline pathogenic BRCA1 and/or 2 mutation or 35 HRD-related gene alterations
age > 19 years
ECOG performance status 0 - 2
Patient has HER2-negative breast cancer with IHC and/or FISH (or SISH, CISH)
Patient has ER positive and/or PgR positive breast cancer by local laboratory testing
Patient is premenopausal
Patient with treatment history as bellows A. In patients with de novo metastatic breast cancer B. In patients with recurrent metastatic breast cancer, recurrence during or after completion or discontinuation of adjuvant endocrine therapy C. One line of prior cytotoxic chemotherapy in metastatic breast cancer is permitted.
No possibility of pregnancy and urine or serum beta-HCG negative
Adequate bone marrow function (≥ANC 1,500/ul, ≥platelet 100,000/ul, ≥Hemoglobin 9.0 g/dl)
Adequate renal function (≤ serum creatinine 1.5 mg/dl or CCr ≥ 650 ml/min)
Adequate liver function (≤ serum bilirubin 2.0 mg/dl, ≤ AST/ALT x 3 upper normal limit)
Patients who were already established on bisphosphonate therapy or denosumab may continue.
Patient agreed to use effective contraception or not of childbearing potential.
Written informed consent
Patients agreed to offer tumor tissue and blood for biomarker analysis
Exclusion Criteria:
Postmenopausal women
Serious uncontrolled intercurrent infections within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment
Serious intercurrent medical or psychiatric illness, including active cardiac disease
Pregnancy or breast feeding within 5 months after the last dose of atezolizumab
Second primary malignancy
Patients has received previous endocrine treatments in the metastatic setting
Patients has received previous aromatase inhibitor
Patients has received previous treatment with CDK 4/6 inhibitors, PARP1 inhibitors, and immune check point inhibitors
Symptomatic visceral metastases, which means lymphangitic lung metastasis and/or symptomatic hepatic metastases
Known brain metastases, symptomatic or asymptomatic
History of clinically significant liver disease, current alcohol abuse or known active infection
History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computerised tomography (CT) scan
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 of 1st Treatment or anticipation that a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months after the last dose of atezolizumab
Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug prior to Cycle 1 Day 1 of 1st Treatment
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1 of 1st Treatment, or anticipated requirement for systemic immunosuppressive medications during the trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yeon Hee Park, phD
Phone
82-2-3410-1780
Email
yeonh.park@samsung.com
First Name & Middle Initial & Last Name or Official Title & Degree
hyunjung shin, CRA
Phone
070-7014-4159
Email
hjds.shin@samsung.com
Facility Information:
Facility Name
Samsung mendical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yeon Hee Park, phD
Phone
82-2-3410-1780
Email
yeonh.park@samsung.com
12. IPD Sharing Statement
Plan to Share IPD
No
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PALbociclib Endocrine Therapy Followed by Talazo vs. Talazoz-Atezo Study
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