Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer

Status:	Active, not recruiting
Conditions:	Breast Cancer, Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	3/15/2019
Start Date:	June 15, 2017
End Date:	February 5, 2021

A Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer

The investigators propose to conduct a study to test an alternative dosing schedule of
palbociclib. With the current three-week on and one week off schedule, a significant number
of patients develop grade 3 or higher degree of neutropenia and require dose reduction and
sometimes discontinuation. This potentially compromises the efficacy of the drug. In
addition, as the half-life of palbociclib is 27 hours, 1 week break with the standard 3 weeks
on and 1 week off dosing schedule could potentially lead to recovery of Rb phosphorylation
during the off week. Hence, the investigators propose a 5 days on and 2 days off schedule
each week without any weeks off drug. Although the cumulative doses each 28-day cycle is
roughly the same with this schedule compared to conventional dosing, the bone marrow is not
exposed to the drug continuously for 21 days and rather gets frequent breaks from therapy.
The investigators hypothesize that the 5 days on and 2 days off schedule is more tolerable
with less frequent high grade neutropenia and dose interruption/reduction. In addition, this
schedule also provides for a more continuous drug delivery to the patient since there is not
a week's break in therapy, which could ultimately prove to be more efficacious.

Inclusion Criteria:

- Histologically confirmed metastatic ER+ and/or PR+ and HER2- breast cancer who are
candidates for palbociclib in combination with either letrozole or fulvestrant per
treating physician.

- Presence of measurable or non-measurable disease by RECIST 1.1 criteria.

- One prior systemic therapy in the metastatic setting is allowed, but patients who have
not had any prior systemic therapies in the metastatic setting are also eligible.

*Note: patients who were started on endocrine therapy monotherapy as their 1st line or
2nd line systemic therapy in the metastatic setting for no more than 28 days and
without clinical progression prior to the initiation of the study drug therapy are
allowed to enroll on the study as their 1st line or 2nd line therapy, respectively.

- At least 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Total bilirubin ≤ institutional upper limit of normal (IULN) or total bilirubin ≤ 3.0
x IULN with direct bilirubin within normal range in patients with documented Gilbert's
syndrome

- AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN (up to 5 x IULN in patients with liver disease)

- Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum
creatinine levels above institutional normal (calculated by Creatinine Clearance
Estimate by Cockcroft-Gault Equation)

- Pre- or post-menopausal women are allowed. If pre- or peri-menopausal, concurrent
ovarian suppression for pre- or peri-menopausal women is required.

- Women of childbearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control, abstinence) prior to study entry and for the duration
of study participation. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she must inform her treating physician immediately.

- Able to swallow and retain oral medication.

- Washout of at least 3 weeks from prior chemotherapy or targeted therapy that induces
myelosuppression and recovery of treatment related adverse events to grade 1 or less,
with the exception of alopecia, is required prior to the start of palbociclib.

- Ability to understand and willingness to sign an Institutional Review Board (IRB)
approved written informed consent document (or that of legally authorized
representative, if applicable).

Exclusion Criteria:

- Prior therapy with any CDK inhibitor.

- Currently receiving any other investigational agents.

- Currently receiving exogenous estrogen replacement (topical vaginal estrogen therapy
is allowed).

- Known brain metastases. Patients with known brain metastases must be excluded from
this clinical trial because of their poor prognosis which could affect the evaluation
of all-cycle adverse events.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to palbociclib or other agents used in the study.

- Receiving any medications or substances that are potent inhibitors or inducers of
CYP3A isoenzymes within 7 days prior to registration.

- Clinically significant history of liver disease.

- A condition that would interfere with enteric absorption.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia.

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 7 days of study entry.

- Known HIV-positivity on combination antiretroviral therapy because of the potential
for pharmacokinetic interactions with palbociclib. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.

We found this trial at

sites

Washington University School of Medicine

660 S Euclid Ave
Saint Louis, Missouri 63110

(314) 362-5000