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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02947685




Registration number
NCT02947685
Ethics application status
Date submitted
26/10/2016
Date registered
28/10/2016

Titles & IDs
Public title
Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer
Scientific title
A Randomized, Open Label, Phase III Trial to Evaluate the Efficacy and Safety of Palbociclib + Anti-HER2 Therapy + Endocrine Therapy vs. Anti-HER2 Therapy + Endocrine Therapy After Induction Treatment for Hormone Receptor Positive (HR+)/HER2-Positive Metastatic Breast Cancer
Secondary ID [1] 0 0
AFT-38
Universal Trial Number (UTN)
Trial acronym
PATINA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER-2 Positive Breast Cancer 0 0
Estrogen Receptor Positive Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - palbociclib
Treatment: Drugs - trastuzumab
Treatment: Drugs - pertuzumab
Treatment: Drugs - letrozole
Treatment: Drugs - Anastrozole
Treatment: Drugs - Exemestane
Treatment: Drugs - Fulvestrant

Experimental: Arm A - Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression

Active comparator: Arm B - AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression


Treatment: Drugs: palbociclib
o Starting dose: 125 mg capsule taken orally once per day for 21 days followed by 7 days off to complete 28 day cycle. Dose reductions: 100 mg, 75 mg. allowed. Number of Cycles: until progression or unacceptable toxicity develops

Treatment: Drugs: trastuzumab
Patients must have received a minimum of 4 and maximum of 8 cycles of induction therapy prior to randomization to Arm A or B, at which point they will continue on antiHER2 therapy and endocrine therapy, with or without palbociclib. Trastuzumab dosing will be determined based on a loading dose of 8mg trastuzumab/kg body weight for Q3WK dosing schedules or a maintenance dose of 6mg/kg trastuzumab/kg dosing weight for Q3WK dosing schedules. Loading dose will be administered on Cycle 1, Day 1.

Treatment: Drugs: pertuzumab
Patients must have received a minimum of 4 and maximum of 8 cycles of induction therapy prior to randomization to Arm A or B, at which point they will continue on antiHER2 therapy and endocrine therapy, with or without palbociclib.Pertuzumab will be administered at a loading dose of 840 mg infusion and then at a maintenance dose of 420 mg q3wks. If patient is within 5 weeks of receiving loading dose at Cycle 1, Day 1, patient may start with maintenance dose of 420 mg.

Treatment: Drugs: letrozole
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for letrozole oral therapy is 2.5 mg orally, once a day.

Treatment: Drugs: Anastrozole
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for anastrozole is 1 mg orally, once a day.

Treatment: Drugs: Exemestane
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for exemestane is 25 mg orally, once a day.

Treatment: Drugs: Fulvestrant
There are several allowed endocrine treatment agents for Arm A and Arm B of this study. Administration is performed on an outpatient, self-administration basis according to local requirements and local standard practice. Endocrine treatment may have started before the patient enters the study. Agents will be administered at the discretion of principal investigator as well as according to standard institutional or regional practice. Recommended dosing regimen for Fulvestrant is 250 mg injections on Day 1 and Day 15 of Cycle 1, and q4weeks thereafter.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) as assessed by Investigator
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
3 and 5 year survival probabilities
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Objective Response Rate (OR: CR or PR)
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Duration of Response (DOR)
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Clinical Benefit Rate (CBR: CR or PR or SD = 24 weeks
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Safety: Type incidence and severity (as graded by NCI CTCAE v 4.0)
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Patient Reported Outcomes
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Incidence of CNS Metastasis
Timepoint [8] 0 0
24 months

Eligibility
Key inclusion criteria
Inclusion Criteria (Preliminary Screening)

1. Signed Preliminary Screening Informed Consent Form obtained prior to any study specific assessments and procedures
2. Age =18 years (or per national guidelines)
3. Patients must have histologically confirmed invasive breast cancer that is metastatic or not amenable for resection or radiation therapy with curative intent. Histological documentation of metastatic/recurrent breast cancer is not required if there is unequivocal evidence for recurrence of the breast cancer.
4. Patients must have histologically confirmed HER2+ and hormone receptor positive (ER+ and/or PR+), metastatic breast cancer. ER, PR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting in the US or certified laboratories for Non-US regions. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.
5. Patients must agree to provide a representative formalin-fixed paraffin-embedded (FFPE) tumor tissue block (preferred) from primary breast or metastatic site (archival) OR at least 15 freshly cut unstained slides from such a block, along with a pathology report documenting HER2 positivity and hormone receptor positivity.
6. Patients should be willing to provide a representative tumor specimen obtained from recently biopsied metastatic disease if clinically feasible. This is recommended but optional tissue.

Inclusion Criteria (Randomization Screening)
7. Signed Main Informed Consent Form obtained prior to any study specific assessments and procedures
8. Age = 18 years (or per national guidelines)
9. ECOG performance status 0-1
10. Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
11. Serum or urine pregnancy test must be negative within 7 days of randomization in women of childbearing potential. Pregnancy testing does not need to be pursued in patients who are judged as postmenopausal before randomization, as determined by local practice, or who have undergone bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation. Women of childbearing potential and male patients randomized into the study must use adequate contraception for the duration of protocol treatment which is 6 months after the last treatment with palbociclib if they are in Arm A and for 7 months after last treatment with trastuzumab if in either Arm A or Arm B Adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male sterilization OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream / suppository).
12. Resolution of all acute toxic effects of prior induction anti-HER2-based chemotherapy regimen to NCI CTCAE version 4.0 Grade =1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion) 12 weeks between last dose of chemotherapy-anti-HER2therapy and randomization are allowed. Endocrine therapy could start before study randomization.
13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Prior Treatment Specifics
14. Patients may or may not have received neo/adjuvant therapy, but must have a disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis =6 months.
15. Patients must have received an acceptable, standard, chemotherapy containing anti-HER2 based induction therapy for the treatment of metastatic breast cancer prior to study enrollment. For this study, chemotherapy is limited to a taxane or vinorelbine (only for trastuzumab-based regimen). Eligible patients are expected to have completed 6 cycles of chemotherapy containing anti-HER2-therapy treatment. A minimum of 4 cycles of treatment is acceptable for patients experiencing significant toxicity associated with treatment as long as they are without evidence of disease progression (i.e. CR, PR or SD). The maximum number of cycles is 8. Patients can randomize immediately following completion of their induction therapy, or for those who have already completed induction, a gap of 12 weeks between their last infusion/dose of induction therapy and the C1D1 visit is permitted. Patients are eligible provided they are without evidence of disease progression by local assessment (i.e. CR, PR or SD).
16. Patients with a history or presence of asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:

* Disease outside the CNS is present.
* No evidence of interim progression between the completion of induction therapy and the screening radiographic study
* No history of intracranial hemorrhage or spinal cord hemorrhage
* Not requiring anti-convulsants for symptomatic control
* Minimum of 3 weeks between completion of CNS radiotherapy and Cycle 1 Day 1 and recovery from significant (Grade = 3) acute toxicity with no ongoing requirement for corticosteroid

Baseline Body Function Specifics
17. Absolute neutrophil count = 1,000/mm3
18. Platelets = 100,000/mm3
19. Hemoglobin = 10g/dL
20. Total serum bilirubin = ULN; or total bilirubin = 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
21. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) = 3 × institutional ULN (=5 x ULN if liver metastases are present).
22. Serum creatinine below the upper limit of normal (ULN) of the institutional normal range or creatinine clearance = 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
23. Left ventricular ejection fraction (LVEF) = 50% at baseline as determined by either ECHO or MUGA
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (Randomization)

1. Concurrent therapy with other Investigational Products.
2. Prior therapy with any CDK 4/6 inhibitor.
3. History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
4. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization (see Section 8.6.3 for list of strong inhibitors or inducers of CYP3A isoenzymes).
5. Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation.
6. Pregnant women, or women of childbearing potential without a negative pregnancy test (serum or urine) within 7 days prior to randomization, irrespective of the method of contraception used, are excluded from this study because the effect of palbociclib on a developing fetus is unknown. Breastfeeding must be discontinued prior to study entry.
7. Patients on combination antiretroviral therapy, i.e. those who are HIV-positive, are ineligible because of the potential for pharmacokinetic interactions or increased immunosuppression with palbociclib.
8. QTc interval >480 msec, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
9. Patients with clinically significant history of liver disease, including viral or other known hepatitis, current alcohol abuse, or cirrhosis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2026
Actual
Sample size
Target
496
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Monash Health - Clayton
Recruitment hospital [2] 0 0
St. Vincent's Hospital, Sydney Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [3] 0 0
The Canberra Hospital - Garran
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre, Royal Melbourne Hospital - Melbourne
Recruitment hospital [5] 0 0
Breast Cancer Research Centre-WA - Nedlands
Recruitment hospital [6] 0 0
Icon Cancer Care - South Brisbane
Recruitment hospital [7] 0 0
Mater Cancer Care Centre - South Brisbane
Recruitment hospital [8] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [9] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Clayton
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Garran
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Nedlands
Recruitment postcode(s) [6] 0 0
- South Brisbane
Recruitment postcode(s) [7] 0 0
- Waratah
Recruitment postcode(s) [8] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
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Illinois
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Kansas
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Louisiana
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United States of America
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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New Jersey
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New Mexico
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Caen
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Cholet
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Dijon
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Lille
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Lyon
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Nice
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Paris
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Rouen
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Saint-Cloud
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Saint-Priest-en-Jarez
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Strasbourg
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France
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Toulouse
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Villejuif
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Germany
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Berlin
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Bielefeld
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Bottrop
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Düsseldorf
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Essen
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Frankfurt
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Hameln
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Hannover
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Karlsruhe
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Germany
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Kiel
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Köln
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Munster
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Germany
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Münster
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Germany
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Oldenburg
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Germany
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Schweinfurt
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Germany
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Wiesbaden
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Italy
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Bologna
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Italy
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Cona
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Italy
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Milano
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Italy
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Segrate
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Italy
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Udine
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New Zealand
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Auckland
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Portugal
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Lisboa
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Portugal
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Loures
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Portugal
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Porto
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Spain
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Barcelona
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Madrid
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Spain
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Murcia
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Spain
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Málaga
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Spain
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Navarro
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Spain
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Salamanca
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Spain
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Santiago
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Spain
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Seville
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Spain
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Tarragona
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Spain
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Valencia

Funding & Sponsors
Primary sponsor type
Other
Name
Alliance Foundation Trials, LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Pfizer
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
German Breast Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Fondazione Michelangelo
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
PrECOG, LLC.
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Breast Cancer Trials, Australia and New Zealand
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Syneos Health
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
SOLTI Breast Cancer Research Group
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
UNICANCER
Address [8] 0 0
Country [8] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results not provided in https://clinicaltrials.gov/study/NCT02947685