Clinical Trials /

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



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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:



Phase 3

Trial Eligibility



  • Brief Title: Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat 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

Clinical Trial IDs

  • NCT ID: NCT02947685


  • HER-2 Positive Breast Cancer
  • Estrogen Receptor Positive Breast Cancer


palbociclibIbranceArm A
trastuzumabHerceptinArm A
pertuzumabPerjetaArm A
letrozoleFemaraArm A
AnastrozoleArimidexArm A
ExemestaneAromasinArm A
FulvestrantFaslodexArm A


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.

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

Trial Arms

Arm AExperimentalPalbociclib 125 mg daily + AntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestratnt) until confirmed disease progression
  • palbociclib
  • trastuzumab
  • pertuzumab
  • letrozole
  • Anastrozole
  • Exemestane
  • Fulvestrant
Arm BActive ComparatorAntiHER2 Therapy (trastuzumab/pertuzumab) q3wks + Endocrine Therapy (letrozole, anastrozole, exemstane OR fulvestrant) until confirmed disease progression
  • pertuzumab
  • letrozole
  • Anastrozole
  • Exemestane
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria (Screening)

          1. Signed informed consent obtained prior to any study specific assessments and

          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

          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

         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

          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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) as assessed by Investigator
Time Frame:24 months
Safety Issue:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:24 months
Safety Issue:
Measure:3 and 5 year survival probabilities
Time Frame:24 months
Safety Issue:
Measure:Objective Response Rate (OR: CR or PRR)
Time Frame:24 months
Safety Issue:
Measure:Duration of Response (DOR)
Time Frame:24 months
Safety Issue:
Measure:Clinical Benefit Rate (CBR: CR or PR or SD ≥ 24 weeks
Time Frame:24 months
Safety Issue:
Measure:Safety: Type incidence and severity (as graded by NCI CTCAE v 4.0)
Time Frame:24 months
Safety Issue:
Description:seriousness and attribution to the study medications of AEs and any laboratory abnormalities
Measure:Patient Reported Outcomes
Time Frame:24 months
Safety Issue:
Description:Time to symptom progression (FACT-B PFB-TOI), breast cancer specific health treatment related quality of life and general health status


Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance Foundation Trials, LLC.

Trial Keywords

  • breast cancer
  • malignant tumor of the breast
  • HER2+
  • HR+
  • metastatic breast cancer

Last Updated

May 30, 2017