Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Fulvestrant

Letrozole

Palbociclib

Goserelin

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Protein Kinase Inhibitors

* Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle).
* Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle.
* Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter.
* Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only.
* Optional research biopsy at baseline and progression
* Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression

Palbociclib at a dose of 125 mg should be taken by mouth with food on a 5 days on/2 days off schedule

Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle, at a dose of 2.5 mg.

Patients who are receiving fulvestrant will receive it at a dose of 500 mg as two 5 mL intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter.

Patients may consent to paired tumor biopsies at baseline and time of progression.

Optional research biopsy

Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- and peri-menopausal women only.

-Blood will be drawn at the following time points for serum, plasma, cfDNA, and germline DNA (only at baseline):

* Baseline
* C1D15
* C2D1
* Every 2-3 months thereafter (to coincide with imaging studies)
* Time of progression

Research blood draw

-Baseline, cycle 2 day 1, post 2 or 3 months of therapy (to coincide with first tumor imaging), and progression

Circulating tumor cell blood draw

Tumor biopsy (optional)

Cynthia X Ma, M.D., Ph.D.

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.

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

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

* The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
* Grade 3 neutropenia: \<1000-500/mm\^3; \<1.0-0.5 x 10e9/L
* Grade 4 neutropenia: \<500/mm\^3; \<0.5 x 10e9/L

-Percentage of participants who have a palbociclib dose reduction during treatment

-Percentage of participants who have a palbociclib dose interruption during treatment

-Percentage of participants who discontinue palbociclib due to adverse event

* The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
* Relationship of possible, probably, or definitely related.

* PFS will be followed from start of treatment to time of progression or death, whichever occurs first.
* Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis).
* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

* Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis).
* Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
* Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Pfizer

Washington University School of Medicine

Palbociclib + Letrozole or + Fulvestrant

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Cynthia X. Ma, M.D., Ph.D.

The following participants were not evaluable for this outcome measure: 4 participants did not take palbociclib dose as per protocol and were without dose-limiting toxicity; 2 participants withdrew in cycle 1, and 1 participant went off treatment in cycle 1 due to adverse events unrelated to the study.

Rate of Grade 3 or Higher Neutropenia

Rate of Palbociclib Dose Reduction

Rate of Palbociclib Dose Interruption

Rate of Palbociclib Discontinuation

Grade 1-2 anemia

Grade 3-4 anemia

Grade 1-2 blurred vision

Grade 1/2 constipation

Grade 1-2 diarrhea

Grade 1-2 dyspepsia

Grade 1-2 gastric ulcer

Grade 1-2 mucositis oral

Grade 1-2 nausea

Grade 1-2 oral dysesthesia

Grade 1-2 vomiting

Grade 1-2 chills

Grade 1-2 fatigue

Grade 1-2 fever

Grade 1-2 diverticulitis

Grade 3-4 sepsis

Grade 1-2 urinary tract infection

Grade 1-2 bruising

Grade 1-2 radiation recall reaction (dermatologic)

Grade 1-2 alanine aminotransferase increased

Grade 3-4 alanine aminotransferase increased

Grade 1-2 alkaline phosphatase increased

Grade 1-2 aspartate aminotransferase increased

Grade 3-4 aspartate aminotransferase increased

Grade 1-2 blood bilirubin increased

Grade 1-2 creatinine increased

Grade 1-2 hemoglobin increased

Grade 1-2 lymphocyte count decreased

Grade 3-4 lymphocyte count decreased

Grade 1-2 neutrophil count decreased

Grade 3-4 neutrophil count decreased

Grade 1-2 platelet count decreased

Grade 3-4 platelet count decreased

Grade 1-2 weight loss

Grade 3-4 weight loss

Grade 1-2 white blood cell decreased

Grade 3-4 white blood cell decreased

Grade 1-2 anorexia

Grade 3-4 hyperglycemia

Grade 1-2 hypermagnesemia

Grade 1-2 hypoalbuminemia

Grade 1-2 hypocalcemia

Grade 1-2 hypokalemia

Grade 1-2 hyponatremia

Grade 1-2 arthralgia

Grade 1-2 arthritis

Grade 1-2 back pain

Grade 1-2 bone pain

Grade 1-2 leg stiffness

Grade 1-2 muscle cramps

Grade 1-2 myalgia

Grade 1-2 neck pain

Grade 1-2 osteonecrosis of jaw

Grade 1-2 pain in extremity

Grade 1-2 dizziness

Grade 3-4 dizziness

Grade 1-2 dysgeusia

Grade 1-2 headache

Grade 1-2 spasticity

Grade 1-2 depression

Grade 1-2 insomnia

Grade 1-2 mood swings

Grade 1-2 breast pain

Grade 1-2 vaginal dryness

Grade 1-2 epistaxis

Grade 1-2 sore throat

Grade 1-2 voice alteration

Grade 1-2 alopecia

Grade 1-2 brittle nails

Grade 1-2 dry skin

Grade 1-2 hyperhidrosis

Grade 1-2 itchy skin

Grade 1-2 nail loss

Grade 1-2 oral fissure

Grade 1-2 rash acneiform

Grade 1-2 rash maculo-papular

Grade 1-2 hot flashes

Grade 1-2 hypertension

Grade 3-4 thromboembolic event

Adverse Event Profile of Palbociclib

Kaplan-Meier Estimate of Progression-free Survival (PFS)

Overall Response Rate (Complete Response + Partial Response)

Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months)

Overall Study

Spots Global Cancer Trial Database for tumor biopsy (optional)