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Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer (PATINA)

This study is currently recruiting participants.
Verified July 2017 by Alliance Foundation Trials, LLC.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02947685
First Posted: October 28, 2016
Last Update Posted: July 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Pfizer
German Breast Group (GBG)
Fondazione Michelangelo
PrECOG, LLC.
Breast Cancer Trials, Australia and New Zealand
Alliance Foundation Trials Biorepository - Washington State University
Alliance Foundation Trials Central Imaging Core Lab - Ohio State University
Mastering Breast Cancer Initiative, LLC
Mayo Clinic Statistics and Data Center
INC Research
SOLTI Breast Cancer Research Group
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.
  Purpose
The primary objective of this study is to demonstrate that the combination of palbociclib with anti-HER2 therapy plus endocrine therapy is superior to anti-HER2-based therapy plus endocrine therapy alone in improving the outcomes of subjects with hormone receptor-positive, HER2+ metastatic breast cancer.

Condition Intervention Phase
HER-2 Positive Breast Cancer Estrogen Receptor Positive Breast Cancer Drug: palbociclib Drug: trastuzumab Drug: pertuzumab Drug: letrozole Drug: Anastrozole Drug: Exemestane Drug: Fulvestrant Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Alliance Foundation Trials, LLC.:

Primary Outcome Measures:
  • Progression-free survival (PFS) as assessed by Investigator [ Time Frame: 24 months ]

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 24 months ]
  • 3 and 5 year survival probabilities [ Time Frame: 24 months ]
  • Objective Response Rate (OR: CR or PRR) [ Time Frame: 24 months ]
  • Duration of Response (DOR) [ Time Frame: 24 months ]
  • Clinical Benefit Rate (CBR: CR or PR or SD ≥ 24 weeks [ Time Frame: 24 months ]
  • Safety: Type incidence and severity (as graded by NCI CTCAE v 4.0) [ Time Frame: 24 months ]
    seriousness and attribution to the study medications of AEs and any laboratory abnormalities

  • Patient Reported Outcomes [ Time Frame: 24 months ]
    Time to symptom progression (FACT-B PFB-TOI), breast cancer specific health treatment related quality of life and general health status


Other Outcome Measures:
  • Trough Plasma concentration of palbociclib, trastuzumab and pertuzumab [ Time Frame: Palbociclib PK assessment: Day 22, Cycle 1, No; Pertuzumab, Trastuzumab PK assessment: Day 1, Cycle 4 ]
    only for patients enrolled in the US

  • PIK3CA genotype assessed in circulating cfDNA [ Time Frame: Day 1, Cycle 1, Day 1, Cycle 4, End of Treatment, approx 24 months ]
  • Tumor tissue biomarkers including genes, proteins, and RNA expression [ Time Frame: Baseline ]

Estimated Enrollment: 496
Actual Study Start Date: June 21, 2017
Estimated Study Completion Date: August 31, 2024
Estimated Primary Completion Date: October 31, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Palbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression
Drug: 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
Other Name: Ibrance
Drug: 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.
Other Name: Herceptin
Drug: 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.
Other Name: Perjeta
Drug: 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.
Other Name: Femara
Drug: 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.
Other Name: Arimidex
Drug: 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.
Other Name: Aromasin
Drug: 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.
Other Name: Faslodex
Active Comparator: Arm B
AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression
Drug: 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.
Other Name: Perjeta
Drug: 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.
Other Name: Femara
Drug: 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.
Other Name: Arimidex
Drug: 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.
Other Name: Aromasin
Drug: 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.
Other Name: Faslodex

Detailed Description:
Subjects will be randomized into one of two treatment arms following minimum of 4 and maximum of 8 cycles of induction treatment with anti-HER2 therapy. Arm A subjects will receive the experimental therapy, palbociclib, in addition to their current anti-HER2 therapy and endocrine therapy. Arm B subjects will continue to receive the anti-HER2 therapy. It is expected that the addition of palbociclib to the first-line treatment of HER2 disease will delay the onset of therapeutic resistance and ultimately prolong the survival of patients with metastatic breast cancer. The study is designed to treat the subset of patients with HER2+ disease who are also hormone receptor positive (HR+). It is also expected that palbociclib will modulate the endocrine resistance in HER2+/HR+ disease and potentiate the benefits of anti-HER2 therapy. Lastly, the current study includes a comprehensive molecular characterization of the disease at study entrance which will allow us to investigate the benefits of palbociclib in subsets of HER2+/HR+ disease such as PIK3CA mutant.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (Screening)

  1. Signed informed consent obtained prior to any study specific assessments and procedures
  2. Age ≥18 years (or per national guidelines)
  3. Participants 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. Representative formalin-fixed paraffin-embedded (FFPE) tumor tissue block (preferred) or at least 15 unstained slides along with a pathology report documenting HER2 positivity and hormone receptor positivity
  6. Representative tumor specimen obtained from metastatic disease if clinically feasible. This could include tumor obtained from metastatic biopsies performed for diagnostic purpose or biopsies performed as part of the current study.

    Inclusion Criteria (Randomization)

  7. Signed informed consent 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 and for 6 months after the last treatment with palbociclib if they are in Arm A. 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) 3-6 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
  14. Evidence of (a) personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study before any study specific activity is performed Prior Treatment Specifics
  15. 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.
  16. 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 are eligible provided they are without evidence of disease progression by local assessment (i.e. CR, PR or SD).
  17. Participants with a history of treated 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 CNS directed 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
  18. Absolute neutrophil count ≥ 1,000/mm3
  19. Platelets ≥ 100,000/mm3
  20. Hemoglobin ≥ 10g/dL
  21. Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
  22. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 1.5 × institutional ULN.
  23. Serum creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
  24. Left ventricular ejection fraction (LVEF)≥ 50% at baseline (within 42 days of randomization) as determined by either ECHO or MUGA

Exclusion Criteria (Randomization)

  1. Concurrent therapy with other Investigational Products.
  2. Prior therapy with any CDK 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.
  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 >480msec, 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02947685


Contacts
Contact: Jane S Lanzillotti, MS 617-735-7511 jlanzillotti@alliancefoundationtrials.org
Contact: Meryl M Pereji, MS 617-732-7380 mpereji@alliancefoundationtrials.org

Locations
United States, Alabama
Southern Cancer Center Recruiting
Mobile, Alabama, United States, 36608
Contact: Karla Childers    251-433-9899    karla.childers@southerncancercenter.com   
Contact: Kristi Weir    251-433-9899    kristi.weir@southerncancercenter.com   
Principal Investigator: Brian Heller, MD         
United States, Illinois
Ingalls Memorial Hospital Recruiting
Harvey, Illinois, United States, 60426
Contact: Margaret Marriott    708-915-6119    mmarriott@ingalls.org   
Principal Investigator: Kimberly Kruczek, MD         
Illinois CancerCare, P.C. Recruiting
Peoria, Illinois, United States, 61615
Contact: Ashton Todd-Hitchcock    309-243-3000      
Contact: Trupti Sherbet    309-243-3000    tsherbet@illinoiscancercare.com   
Principal Investigator: Nguyet Le-Lindqwister, MD         
OSF Saint Anthony Medical Center Recruiting
Rockford, Illinois, United States, 61108
Contact: Mark Rogers    815-227-2674    mark.w.rogers@osfhealthcare.org   
Principal Investigator: Shylenda Sreenivasappa, MD         
United States, Iowa
Medical Oncology & Hematology Associates Recruiting
Des Moines, Iowa, United States, 50309
Contact: Peggy Wilson    515-241-3305    pwilson@iora.org   
Contact: Missy Stravers    515-241-3305    mstravers@iora.org   
Principal Investigator: Robert Behrens, MD         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Kimberly Mueller    402-354-7938    kimberly.mueller@nmhs.com   
Principal Investigator: Kirsten Leu, MD         
United States, Oklahoma
Cancer Centers of Southwest Oklahoma Recruiting
Lawton, Oklahoma, United States, 73505
Contact: Susie McCoy    580-536-2121    susie.mccoy@ccswok.org   
Principal Investigator: Jose Eugenio Najera, MD         
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Pfizer
German Breast Group (GBG)
Fondazione Michelangelo
PrECOG, LLC.
Breast Cancer Trials, Australia and New Zealand
Alliance Foundation Trials Biorepository - Washington State University
Alliance Foundation Trials Central Imaging Core Lab - Ohio State University
Mastering Breast Cancer Initiative, LLC
Mayo Clinic Statistics and Data Center
INC Research
SOLTI Breast Cancer Research Group
Investigators
Study Chair: Otto Metzger, MD Alliance Foundation Trials, LLC.
  More Information

Publications:
Finn, R.S., et al., PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2- advanced breast cancer (ABC). ASCO Meeting Abstracts, 2016. 34(15_suppl): p. 507.
Pfizer, Inc. Palbociclib (PD-0332991): Investigator's Brochure. N.p.: Pfizer, 2015. Print.

Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT02947685     History of Changes
Other Study ID Numbers: AFT-38
First Submitted: October 26, 2016
First Posted: October 28, 2016
Last Update Posted: July 18, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alliance Foundation Trials, LLC.:
breast cancer
malignant tumor of the breast
HER2+
HR+
metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Exemestane
Anastrozole
Palbociclib
Pertuzumab
Trastuzumab
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Protein Kinase Inhibitors