Clinical Trials /

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

NCT02947685

Description:

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:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • 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

  • ORG STUDY ID: AFT-38
  • NCT ID: NCT02947685

Conditions

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

Interventions

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

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
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 (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

        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
      
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:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:24 months
Safety Issue:
Description:Defined as time from date of randomization to date of death due to any cause
Measure:3 and 5 year survival probabilities
Time Frame:24 months
Safety Issue:
Description:Survival probabilities will be estimated using the Kaplan-Meier method
Measure:Objective Response Rate (OR: CR or PRR)
Time Frame:24 months
Safety Issue:
Description:Defined as complete response (CR) or partial response (PR) according to RECIST v1.1
Measure:Duration of Response (DOR)
Time Frame:24 months
Safety Issue:
Description:Defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death from any cause, whichever occurs first
Measure:Clinical Benefit Rate (CBR: CR or PR or SD ≥ 24 weeks
Time Frame:24 months
Safety Issue:
Description:The Clinical Benefit Rate (CBR) on each treatment arm will be estimated by dividing the number of patients with CR, PR, or SD/Non-CR and Non-PD (for patients with measurable disease) ≥ 24 weeks by the number of patients randomized to the treatment arm.
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

Details

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

November 24, 2020