Alternative Dosing Schedule of Palbociclib and Letrozole or Fulvestrant with or without Goserelin Acetate in Treating Patients with Metastatic Hormone Receptor Positive Breast Cancer

Status: Active

Description

This phase II trial studies the side effects of an alternative dosing schedule of palbociclib and letrozole or fulvestrant with or without goserelin acetate in treating patients with hormone receptor positive breast cancer that has spread to other places in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone can cause the growth of breast tumor cells. Hormone therapy using letrozole, fulvestrant, and goserelin acetate may fight hormone receptor positive breast cancer by blocking the use of estrogen and progesterone by the tumor cells. Giving an alternative dosing schedule of palbociclib and letrozole or fulvestrant with or without goserelin acetate may work better in treating patients with hormone receptor positive breast cancer.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed metastatic ER positive (+) and/or PR+ and HER2 negative (-) 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 Response Evaluation Criteria in Solid Tumors (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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • 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
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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 m^2 for patients with serum creatinine levels above institutional normal (IULN) (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 therapy (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 human immunodeficiency virus (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

Locations & Contacts

Missouri

Saint Louis
Siteman Cancer Center at Christian Hospital
Status: Active
Contact: Cynthia Xiuguang Ma
Phone: 314-362-9383
Email: cynthiaxma@wustl.edu
Siteman Cancer Center at Washington University
Status: Active
Contact: Cynthia Xiuguang Ma
Phone: 314-362-9383
Email: cynthiaxma@wustl.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the rate of grade 3 or higher neutropenia in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule within the first 29 days of treatment.

SECONDARY OBJECTIVES:

I. To determine the rate of grade 3 or higher neutropenia in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule during all cycles.

II. To determine the rate of palbociclib dose reduction, interruption, or discontinuation.

III. To determine the adverse events profile of palbociclib given on a 5 days on/2 days off schedule.

IV. To determine the progression free survival in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule.

V. To determine the overall response rate (complete response [CR]+partial response [PR]) in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule.

VI. To determine the clinical benefit rate (CR+PR+stable disease [SD] for at least 6 months) in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule.

EXPLORATORY OBJECTIVES:

I. To assess changes in cell free deoxyribonucleic acid (DNA) mutation profile, including mutations in TP53, PIK3CA, ESR1, and RB1 and their correlation with treatment response.

II. To correlate archival tumor mutation profile and retinoblastoma (RB) protein status with treatment response.

III. To assess intrinsic and acquired resistance mechanisms to palbociclib in tumor samples collected at baseline and at progression.

IV. To assess changes in serum thymidine kinase activity and correlate with treatment response and absolute neutrophil count.

V. To establish patient derived xenograft (PDX) models from tumor biopsies before treatment and at progression for future studies.

VI. To assess baseline and changes in circulating tumor cell (CTC) gene expression profiles and to correlate with treatment response.

OUTLINE:

Patients receive palbociclib orally (PO) on days 1-5, 8-12, 15-19, and 22-26. Patients also receive letrozole PO daily on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and day 1 only of each course thereafter per physician choice. Patients who are pre- and peri-menopausal also receive goserelin acetate subcutaneously (SC) on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Cynthia Xiuguang Ma

Trial IDs

Primary ID 201612098
Secondary IDs NCI-2016-02008
Clinicaltrials.gov ID NCT03007979