Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Palbociclib; Aromatase Inhibitor
Intervention description: CDK 4/6 inhibitor; Endocrine Therapy
Intervention MeSH terms: Tamoxifen; Letrozole; Palbociclib; Anastrozole; Exemestane; Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 162.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer

Summary:

      This research study is evaluating a drug called Palbociclib in combination with endocrine
      therapy as a possible treatment for hormone receptor positive breast cancer.

        -  Palbociclib is a drug that may stop cancer cells from growing. Palbociclib blocks
           activity of two closely related enzymes (proteins that help chemical reactions in the
           body occur), called Cyclin D Kinases 4 and 6 (CDK 4/6). These proteins are part of a
           pathway, or a sequence of steps which is known to regulate cell growth. Laboratory
           testing has suggested palbociclib may stop the growth of hormone receptor positive
           breast cancer.

        -  Endocrine therapy prevents breast cancer cell growth by blocking estrogen stimulation.
           During this study endocrine therapy will either be tamoxifen or an aromatase inhibitor.
           It is standard of care for premenopausal women to take tamoxifen and for postmenopausal
           women to take either an aromatase inhibitor or tamoxifen after a diagnosis of hormone
           receptor positive breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have histologically confirmed hormone receptor positive (HR+) HER2
             negative stage II (except T2N0) or stage III invasive breast cancer. Evaluation for
             metastatic disease is not required in the absence of symptoms.

          -  Men and both pre- and postmenopausal women are eligible.

          -  Prior Treatment:

               -  Participants may have received (neo)adjuvant chemotherapy, but must be at least
                  30 days after last dose, with no more than grade 1 residual toxicity at time of
                  screening.

               -  Participants may have received adjuvant radiotherapy, but must be at least 30
                  days after last dose , with no more than grade 1 residual toxicity at the time of
                  screening.

               -  If most recent therapy was surgery, participants must be at least 30 days out
                  from definitive surgery with no active wound healing complications.

          -  Participants must have demonstrated ability to tolerate endocrine therapy by prior
             successful completion of at least 1 month of tamoxifen or aromatase inhibitor (AI)
             therapy without significant adverse events, and in the opinion of the treating
             physician any ongoing toxicity does not preclude ability to continue on tamoxifen or
             AI for at least a projected 2 year continuous duration. Ongoing use of any endocrine
             therapy, including tamoxifen, letrozole, anastrozole, or exemestane, is allowed.
             Patients may enroll within 2 years of beginning endocrine therapy, as long as there is
             a plan for at least 2 more years of adjuvant endocrine therapy.

          -  ECOG performance status 0-1

          -  Age ≥18 years.

          -  Normal organ and marrow function

          -  Baseline QTc ≤ 480 ms

          -  The effects of palbociclib on the developing human fetus are unknown. Women who might
             become pregnant must use adequate contraception

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Concurrent therapy with other investigational agents.

          -  Prior therapy with any CDK4/6 inhibitor.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to palbociclib.

          -  Participants receiving any medications or substances that are strong inhibitors or
             inducers of CYP3A isoenzymes are ineligible.

          -  Current use of drugs that are known to prolong the QT interval

          -  Subjects with organ allograft requiring immunosuppression.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study. Breastfeeding should be discontinued
             prior to entry onto the study.

          -  Individuals with a history of a different malignancy are ineligible except for the
             following circumstances. Individuals with a history of other malignancies are eligible
             if they have been disease-free for at least 5 years and are deemed by the investigator
             to be at low risk for recurrence of that malignancy. Individuals with the following
             cancers are eligible if diagnosed and treated within the past 5 years: ductal
             carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous
             cell carcinoma of the skin.

          -  No ongoing combination antiretroviral therapy