A Phase 2 interventional study of Palbociclib and Letrozole in Breast Cancer, Breast Carcinoma and Cancer of Breast, sponsored by Washington University School of Medicine. Completed at 2 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-20.
Sponsored by Washington University School of Medicine · Phase 2, Interventional, and Treatment
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 55 is below the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.
Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
Normal bone marrow and organ function as defined below:
Exclusion Criteria:
* 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
Drug: Palbociclib · Drug: Letrozole · Drug: Fulvestrant · Procedure: Optional research biopsy · Drug: Goserelin · Procedure: Research blood draw · Procedure: Circulating tumor cell blood draw · Procedure: Tumor biopsy (optional)
Palbociclib at a dose of 125 mg should be taken by mouth with food on a 5 days on/2 days off schedule
Also known as: Ibrance
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.
Also known as: Femara
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.
Also known as: Faslodex
Patients may consent to paired tumor biopsies at baseline and time of progression.
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.
Also known as: Zoladex
-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
-Baseline, cycle 2 day 1, post 2 or 3 months of therapy (to coincide with first tumor imaging), and progression
-Baseline and progression
Rate of Grade 3 or Higher Neutropenia
* 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
Time frame: Through the first 29 days of treatment
Rate of Grade 3 or Higher Neutropenia
* 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
Time frame: Through 30 day follow-up (estimated to be 25 months)
Rate of Palbociclib Dose Reduction
-Percentage of participants who have a palbociclib dose reduction during treatment
Time frame: Through the completion of treatment (estimated to be 24 months)
Rate of Palbociclib Dose Interruption
-Percentage of participants who have a palbociclib dose interruption during treatment
Time frame: Through the completion of treatment (estimated to be 24 months)
Rate of Palbociclib Discontinuation
-Percentage of participants who discontinue palbociclib due to adverse event
Time frame: Through the completion of treatment (estimated to be 24 months)
Adverse Event Profile of Palbociclib
* 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.
Time frame: Through the 30 day follow-up (estimated to be 25 months)
Kaplan-Meier Estimate of Progression-free Survival (PFS)
* 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).
Time frame: 1 year
Overall Response Rate (Complete Response + Partial Response)
* 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
Time frame: Time of progression (estimated to be 24 months)
Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months)
* 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.
Time frame: Time of progression (estimated to be 24 months)
| Milestone | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Started | 55 |
| Completed | 54 |
| Not completed | 1 |
| Withdrew: Deemed not eligible prior to starting palbociclib | 1 |
* 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
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Rate of Grade 3 or Higher Neutropenia | 10 |
* 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
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Rate of Grade 3 or Higher Neutropenia | 23 |
-Percentage of participants who have a palbociclib dose reduction during treatment
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Rate of Palbociclib Dose Reduction | 13 |
-Percentage of participants who have a palbociclib dose interruption during treatment
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Rate of Palbociclib Dose Interruption | 39 |
-Percentage of participants who discontinue palbociclib due to adverse event
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Rate of Palbociclib Discontinuation | 2 |
* 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.
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Grade 1-2 anemia | 31 |
| Grade 3-4 anemia | 4 |
| Grade 1-2 blurred vision | 1 |
| Grade 1/2 constipation | 5 |
| Grade 1-2 diarrhea | 8 |
| Grade 1-2 dyspepsia | 1 |
| Grade 1-2 gastric ulcer | 1 |
| Grade 1-2 mucositis oral | 11 |
| Grade 1-2 nausea | 16 |
| Grade 1-2 oral dysesthesia | 1 |
| Grade 1-2 vomiting | 7 |
| Grade 1-2 chills | 3 |
| Grade 1-2 fatigue | 22 |
| Grade 1-2 fever | 3 |
| Grade 1-2 diverticulitis | 1 |
| Grade 3-4 sepsis | 1 |
| Grade 1-2 urinary tract infection | 1 |
| Grade 1-2 bruising | 1 |
| Grade 1-2 radiation recall reaction (dermatologic) | 1 |
| Grade 1-2 alanine aminotransferase increased | 4 |
| Grade 3-4 alanine aminotransferase increased | 2 |
| Grade 1-2 alkaline phosphatase increased | 4 |
| Grade 1-2 aspartate aminotransferase increased | 4 |
| Grade 3-4 aspartate aminotransferase increased | 1 |
| Grade 1-2 blood bilirubin increased | 1 |
| Grade 1-2 creatinine increased | 2 |
| Grade 1-2 hemoglobin increased | 1 |
| Grade 1-2 lymphocyte count decreased | 23 |
| Grade 3-4 lymphocyte count decreased | 13 |
| Grade 1-2 neutrophil count decreased | 22 |
| Grade 3-4 neutrophil count decreased | 24 |
| Grade 1-2 platelet count decreased | 21 |
| Grade 3-4 platelet count decreased | 1 |
| Grade 1-2 weight loss | 1 |
| Grade 3-4 weight loss | 1 |
| Grade 1-2 white blood cell decreased | 26 |
| Grade 3-4 white blood cell decreased | 26 |
| Grade 1-2 anorexia | 4 |
| Grade 3-4 hyperglycemia | 1 |
| Grade 1-2 hypermagnesemia | 1 |
| Grade 1-2 hypoalbuminemia | 1 |
| Grade 1-2 hypocalcemia | 1 |
| Grade 1-2 hypokalemia | 2 |
| Grade 1-2 hyponatremia | 1 |
| Grade 1-2 arthralgia | 6 |
| Grade 1-2 arthritis | 1 |
| Grade 1-2 back pain | 1 |
| Grade 1-2 bone pain | 1 |
| Grade 1-2 leg stiffness | 1 |
| Grade 1-2 muscle cramps | 1 |
| Grade 1-2 myalgia | 3 |
| Grade 1-2 neck pain | 1 |
| Grade 1-2 osteonecrosis of jaw | 1 |
| Grade 1-2 pain in extremity | 1 |
| Grade 1-2 dizziness | 4 |
| Grade 3-4 dizziness | 1 |
| Grade 1-2 dysgeusia | 5 |
| Grade 1-2 headache | 2 |
| Grade 1-2 spasticity | 1 |
| Grade 1-2 depression | 1 |
| Grade 1-2 insomnia | 3 |
| Grade 1-2 mood swings | 1 |
| Grade 1-2 breast pain | 1 |
| Grade 1-2 vaginal dryness | 1 |
| Grade 1-2 epistaxis | 2 |
| Grade 1-2 sore throat | 1 |
| Grade 1-2 voice alteration | 1 |
| Grade 1-2 alopecia | 19 |
| Grade 1-2 brittle nails | 1 |
| Grade 1-2 dry skin | 2 |
| Grade 1-2 hyperhidrosis | 3 |
| Grade 1-2 itchy skin | 3 |
| Grade 1-2 nail loss | 1 |
| Grade 1-2 oral fissure | 1 |
| Grade 1-2 rash acneiform | 1 |
| Grade 1-2 rash maculo-papular | 1 |
| Grade 1-2 hot flashes | 12 |
| Grade 1-2 hypertension | 2 |
| Grade 3-4 thromboembolic event | 1 |
* 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).
| percentage of participants-Kaplan Meier | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Kaplan-Meier Estimate of Progression-free Survival (PFS) | 67.911 (52.934 to 79.025) |
* 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
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Overall Response Rate (Complete Response + Partial Response) | 18 |
* 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.
| Participants | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months) | 45 |
Collected over Adverse events were collected from start of treatment through 30 days following completion of treatment.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Palbociclib + Letrozole or + Fulvestrant | 3/54 (5.6%) | 15/54 (27.8%) | 54/54 (100%) |
| Event | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| DeathGeneral disorders | 3/54 |
| CellulitisInfections and infestations | 3/54 |
| NauseaGastrointestinal disorders | 2/54 |
| VomitingGastrointestinal disorders | 2/54 |
| Urinary tract infectionInfections and infestations | 2/54 |
| Acute kidney injuryRenal and urinary disorders | 2/54 |
| Thromboembolic eventVascular disorders | 2/54 |
| Chest pain - cardiacCardiac disorders | 1/54 |
| Myocardial infarctionCardiac disorders | 1/54 |
| ConstipationGastrointestinal disorders | 1/54 |
| Event | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| White blood cell count decreasedInvestigations | 52/54 |
| Neutrophil count decreasedInvestigations | 47/54 |
| AnemiaBlood and lymphatic system disorders | 43/54 |
| Lymphocyte count decreasedInvestigations | 40/54 |
| HypertensionVascular disorders | 36/54 |
| FatigueGeneral disorders | 33/54 |
| DiarrheaGastrointestinal disorders | 30/54 |
| NauseaGastrointestinal disorders | 29/54 |
| Platelet count decreasedInvestigations | 23/54 |
| AlopeciaSkin and subcutaneous tissue disorders | 22/54 |
| Age, Continuous(years) | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Median | 61 (34 to 86) |
| Sex: Female, Male(Participants) | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Female | 55 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 55 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 10 |
| White | 45 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Palbociclib + Letrozole or + Fulvestrant |
|---|---|
| United States | 55 |
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Washington University School of Medicine