Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer

A Phase 2 Pilot Feasibility Study of Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive Invasive Breast Carcinoma

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.

After the screening procedures confirms that the participant is able to participate in the study. The participant will be given a dosing diary for each treatment cycle. Each treatment cycle lasts 28 days, during which time the participant will take Palbociclib once a day on days 1-21 of each 28 day cycle and the aromatase inhibitor that the participant is already taking once a day every day. The diary will also include special instructions for taking the study drug(s).

All participants participating in the research study will receive the same dose of Palbociclib.

While participating in the research study the participant will have the following tests and procedures:

• Clinical Exams: The participant will have a physical exam on the first day of the month for first three months of therapy. After that, the participant will have a physical exam every other month until the end of the first year of therapy. After the first year, the participant will have a physical exam every 3 months during the second year of therapy. During the physical exam, the participant will be asked questions about their general health, questions about any problems that they may be experiencing, and any medications they are taking.
• Blood tests: The participant will have blood drawn on the first and fifteenth days of the first three months of therapy. After that, the participant will have blood drawn every month for the remainder of the first year of treatment and the every other month until the end of therapy. These tests will be used to determine if the participant is having any side effects related to the study drug.
• Electrocardiograms (EKG): The participant will have an EKG performed on the first day of the first three months of therapy. After that, the participant will have an EKG every other month until the end of the first year of therapy. After the first year of therapy, the participant will have an EKG every 3 months during the second year of therapy.

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