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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

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.

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

Details

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.

Keywords

HER-2 Positive Breast Cancer Estrogen Receptor Positive Breast Cancer breast cancer malignant tumor of the breast HER2+ HR+ metastatic breast cancer Breast Neoplasms Letrozole Fulvestrant Exemestane Palbociclib Anastrozole Pertuzumab Trastuzumab

Eligibility

You can join if…

Open to people ages 18 years and up

(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. 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. 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 metastatic disease if clinically feasible. This is a recommended but optional research biopsy.

Inclusion Criteria (Randomization Screening)

  1. Signed Main Informed Consent Form obtained prior to any study specific assessments and procedures
  2. Age ≥ 18 years (or per national guidelines)
  3. ECOG performance status 0-1
  4. . Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
  5. . 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 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).
  6. . 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.
  7. . Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Prior Treatment Specifics

  1. . 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.
  2. . 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).
  3. . Participants with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
  4. Disease outside the CNS is present.
  5. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
  6. No history of intracranial hemorrhage or spinal cord hemorrhage
  7. Not requiring anti-convulsants for symptomatic control
  8. 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

  1. . Absolute neutrophil count ≥ 1,000/mm3
  2. . Platelets ≥ 100,000/mm3
  3. . Hemoglobin ≥ 10g/dL
  4. . Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
  5. . Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤3 × institutional ULN (≤5 x ULN if liver metastases are present).
  6. . Serum creatinine within normal institutional limits or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.
  7. . Left ventricular ejection fraction (LVEF) ≥ 50% at baseline as determined by either ECHO or MUGA

You CAN'T join if...

(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

Locations

  • UCSF not yet accepting patients
    San Francisco, California, 94115, United States
  • Mayo Clinic, AZ not yet accepting patients
    Phoenix, Arizona, 85054, United States
  • Huntsman Cancer Institute, University of Utah accepting new patients by invitation only
    Salt Lake City, Utah, 84112, United States
  • Legacy Good Samaritan Hospital accepting new patients by invitation only
    Portland, Oregon, 97210, United States
  • Providence Portland Medical Center accepting new patients
    Portland, Oregon, 97213, United States
  • Multicare Institute for Research and Innovation accepting new patients
    Puyallup, Washington, 98372, United States
  • New Mexico Cancer Care Alliance accepting new patients by invitation only
    Albuquerque, New Mexico, 87131, United States
  • Cancer Centers of Southwest Oklahoma accepting new patients
    Lawton, Oklahoma, 73505, United States
  • Cancer Center of Kansas accepting new patients
    Wichita, Kansas, 67214, United States
  • Nebraska Methodist Hospital accepting new patients by invitation only
    Omaha, Nebraska, 68114, United States
  • University of Nebraska Medical Center accepting new patients by invitation only
    Omaha, Nebraska, 68198, United States
  • Medical Oncology & Hematology Associates accepting new patients
    Des Moines, Iowa, 50309, United States
  • Metro-Minnesota NCI Community Oncology Research Program not yet accepting patients
    Minneapolis, Minnesota, 55416, United States
  • Mayo Clinic, Rochester, MN not yet accepting patients
    Rochester, Minnesota, 55905, United States
  • Washington University School of Medicine accepting new patients
    Saint Louis, Missouri, 63110, United States
  • Illinois CancerCare, P.C. accepting new patients
    Peoria, Illinois, 61615, United States
  • OSF Saint Anthony Medical Center accepting new patients
    Rockford, Illinois, 61108, United States
  • University of Illinois at Chicago accepting new patients
    Chicago, Illinois, 60612, United States
  • Loyola University Chicago not yet accepting patients
    Chicago, Illinois, 60660, United States
  • Ingalls Memorial Hospital accepting new patients by invitation only
    Harvey, Illinois, 60426, United States
  • The University of Chicago Medical Center not yet accepting patients
    Chicago, Illinois, 60637, United States
  • Ochsner Medical Center Jefferson not yet accepting patients
    New Orleans, Louisiana, 70121, United States
  • Vanderbilt University Medical Center not yet accepting patients
    Nashville, Tennessee, 37204, United States
  • West Michigan Cancer Center not yet accepting patients
    Grand Rapids, Michigan, 49503, United States
  • Southern Cancer Center withdrawn
    Mobile, Alabama, 36608, United States
  • St. Elizabeth Healthcare /Edgewood accepting new patients
    Edgewood, Kentucky, 41017, United States
  • Michigan Cancer Research Consortium (St. Joseph Mercy Hospital accepting new patients
    Ann Arbor, Michigan, 48106, United States
  • Ohio State University not yet accepting patients
    Columbus, Ohio, 43210, United States
  • Emory University accepting new patients by invitation only
    Atlanta, Georgia, 30322, United States
  • UPMC (University of Pittsburgh Medical Center) accepting new patients
    Pittsburgh, Pennsylvania, 15213, United States
  • Novant Health Presbyterian Medical Center accepting new patients
    Charlotte, North Carolina, 28204, United States
  • Lexington Medical Center accepting new patients
    West Columbia, South Carolina, 29169, United States
  • Baycare Healthcare (Morton Plant Mease) accepting new patients
    Clearwater, Florida, 33756, United States
  • First Health of the Carolinas Cancer Center not yet accepting patients
    Pinehurst, North Carolina, 28374, United States
  • McLeod Regional Medical Center accepting new patients by invitation only
    Florence, South Carolina, 29506, United States
  • Duke Cancer Institute not yet accepting patients
    Durham, North Carolina, 27710, United States
  • Florida Hospital accepting new patients
    Orlando, Florida, 32804, United States
  • Inova Fairfax Hospital accepting new patients
    Falls Church, Virginia, 22042, United States
  • Georgetown University Medical Center accepting new patients by invitation only
    Washington, District of Columbia, 20007, United States
  • University of Maryland (St. Joseph's Medical Center not yet accepting patients
    Towson, Maryland, 21204, United States
  • University of Maryland, Greenebaum Cancer Center accepting new patients
    Baltimore, Maryland, 21201, United States
  • Johns Hopkins University/Sidney Kimmel Cancer Center not yet accepting patients
    Baltimore, Maryland, 21287, United States
  • Anne Arundel Medical Center accepting new patients by invitation only
    Annapolis, Maryland, 21401, United States
  • Kinston Medical Specialists withdrawn
    Kinston, North Carolina, 28501, United States
  • University of Pennsylvania not yet accepting patients
    Philadelphia, Pennsylvania, 19106, United States
  • Memorial Healthcare System accepting new patients by invitation only
    Hollywood, Florida, 33021, United States
  • University of Miami not yet accepting patients
    Miami, Florida, 33136, United States
  • Mount Sinai Medical Center - FL accepting new patients
    Miami Beach, Florida, 33140, United States
  • St. Joseph's Regional Medical Center accepting new patients
    Paterson, New Jersey, 07503, United States
  • The Valley Hospital, Okonite Research Center not yet accepting patients
    Paramus, New Jersey, 07652, United States
  • Hackensack Medical Center accepting new patients by invitation only
    Hackensack, New Jersey, 07601, United States
  • Dartmouth Hitchcock Medical Center not yet accepting patients
    Lebanon, New Hampshire, 03756, United States
  • Lowell General Hospital accepting new patients by invitation only
    Lowell, Massachusetts, 01854, United States
  • Dana-Farber Cancer Institute accepting new patients by invitation only
    Boston, Massachusetts, 02215, United States
  • New England Cancer Specialists accepting new patients by invitation only
    Scarborough, Maine, 04074, United States
  • EMMC Cancer Care accepting new patients
    Brewer, Maine, 04412, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Alliance Foundation Trials, LLC.
ID
NCT02947685
Phase
Phase 3
Study Type
Interventional
Last Updated
April 26, 2018
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