Brief Summary
This phase II trial studies the side effects and how well palbociclib and letrozole or fulvestrant works in treating patients aged 70 years and older with estrogen receptor positive, HER2 negative 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. Drugs used in chemotherapy, such as letrozole or fulvestrant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib and letrozole or fulvestrant may work better in treating patients with breast cancer. The trial will explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.
Brief Title
Palbociclib and Letrozole or Fulvestrant in Treating Patients With Estrogen Receptor Positive, HER2 Negative Metastatic Breast Cancer
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the safety and tolerability (adverse event rate) of the combination of palbociclib and letrozole or fulvestrant in adults age 70 or older with estrogen receptor-positive, HER2-negative metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To describe the full toxicity profile including all grade 2 and higher adverse events (per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0), specifically estimating the rate of grade 2 and higher myelosuppression (neutropenia, leukopenia, thrombocytopenia, and anemia), neutropenic fever, gastrointestinal (GI) side effects (nausea, diarrhea, decreased appetite, vomiting, mucositis-oral), fatigue, neuropathy, and thromboembolism.
II. To describe rates of dose reductions, dose holds, and hospitalizations. III. To estimate median time to treatment failure, including progression free survival and overall survival.
IV. To estimate the rate of adherence to palbociclib, letrozole and fulvestrant.
V. To explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.
VI. To describe the results of the Overall Treatment Utility (OTU). VII. To determine the degree of agreement between patient-reported adverse events (AEs) using Patient Reported Outcomes (PRO)-CTCAE measures and those reported using traditional collections for AEs.
VIII. To examine the association between sarcopenia and the development of toxicity and adverse events.
OUTLINE:
Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of subsequent courses per Doctor of Medicine (MD) discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 5 years.
I. To estimate the safety and tolerability (adverse event rate) of the combination of palbociclib and letrozole or fulvestrant in adults age 70 or older with estrogen receptor-positive, HER2-negative metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To describe the full toxicity profile including all grade 2 and higher adverse events (per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0), specifically estimating the rate of grade 2 and higher myelosuppression (neutropenia, leukopenia, thrombocytopenia, and anemia), neutropenic fever, gastrointestinal (GI) side effects (nausea, diarrhea, decreased appetite, vomiting, mucositis-oral), fatigue, neuropathy, and thromboembolism.
II. To describe rates of dose reductions, dose holds, and hospitalizations. III. To estimate median time to treatment failure, including progression free survival and overall survival.
IV. To estimate the rate of adherence to palbociclib, letrozole and fulvestrant.
V. To explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.
VI. To describe the results of the Overall Treatment Utility (OTU). VII. To determine the degree of agreement between patient-reported adverse events (AEs) using Patient Reported Outcomes (PRO)-CTCAE measures and those reported using traditional collections for AEs.
VIII. To examine the association between sarcopenia and the development of toxicity and adverse events.
OUTLINE:
Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of subsequent courses per Doctor of Medicine (MD) discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 5 years.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Estrogen Receptor-positive Breast Cancer
HER2/Neu Negative
Stage IV Breast Cancer AJCC v6 and v7
Eligibility Criteria
Inclusion Criteria:
* Documentation of disease: estrogen receptor positive and/or progesterone receptor (PR) positive, HER2 negative metastatic breast cancer; histologic confirmation is required
* Measurable disease or non-measurable disease
* Planning to begin palbociclib for metastatic disease; one prior line of endocrine therapy and/or chemotherapy for metastatic disease is allowed; patients may begin or have already begun endocrine therapy before they start palbociclib treatment, but no more than two weeks prior to registration
* No prior therapy with a CDK inhibitor
* Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade =\< 1 (except alopecia) or to baseline toxicities prior to previous therapy or surgical procedures, prior to registration
* No untreated brain metastases; patients with treated brain metastases must have completed treatment with steroids to be eligible
* No known interstitial lung disease
* No second malignancies other than non-melanoma skin cancers or cervical carcinoma in situ; however, patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for \>= 3 years
* No active infection requiring treatment with antibiotics
* Patients must be able to swallow and retain oral medication
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Patients must be able to read and comprehend English or Spanish
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (1.5 x 10\^9/L)
* Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L)
* Creatinine clearance \>= 30 ml/min calculated using the Cockcroft-Gault formula
* Total serum bilirubin =\< 1.5 upper limit of normal (ULN) (\< 3 ULN if Gilbert's disease)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5.0 x ULN if liver metastases present)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if bone or liver metastases present)
* Documentation of disease: estrogen receptor positive and/or progesterone receptor (PR) positive, HER2 negative metastatic breast cancer; histologic confirmation is required
* Measurable disease or non-measurable disease
* Planning to begin palbociclib for metastatic disease; one prior line of endocrine therapy and/or chemotherapy for metastatic disease is allowed; patients may begin or have already begun endocrine therapy before they start palbociclib treatment, but no more than two weeks prior to registration
* No prior therapy with a CDK inhibitor
* Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade =\< 1 (except alopecia) or to baseline toxicities prior to previous therapy or surgical procedures, prior to registration
* No untreated brain metastases; patients with treated brain metastases must have completed treatment with steroids to be eligible
* No known interstitial lung disease
* No second malignancies other than non-melanoma skin cancers or cervical carcinoma in situ; however, patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for \>= 3 years
* No active infection requiring treatment with antibiotics
* Patients must be able to swallow and retain oral medication
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Patients must be able to read and comprehend English or Spanish
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (1.5 x 10\^9/L)
* Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L)
* Creatinine clearance \>= 30 ml/min calculated using the Cockcroft-Gault formula
* Total serum bilirubin =\< 1.5 upper limit of normal (ULN) (\< 3 ULN if Gilbert's disease)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5.0 x ULN if liver metastases present)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if bone or liver metastases present)
Inclusion Criteria
Inclusion Criteria:
* Documentation of disease: estrogen receptor positive and/or progesterone receptor (PR) positive, HER2 negative metastatic breast cancer; histologic confirmation is required
* Measurable disease or non-measurable disease
* Planning to begin palbociclib for metastatic disease; one prior line of endocrine therapy and/or chemotherapy for metastatic disease is allowed; patients may begin or have already begun endocrine therapy before they start palbociclib treatment, but no more than two weeks prior to registration
* No prior therapy with a CDK inhibitor
* Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade =\< 1 (except alopecia) or to baseline toxicities prior to previous therapy or surgical procedures, prior to registration
* No untreated brain metastases; patients with treated brain metastases must have completed treatment with steroids to be eligible
* No known interstitial lung disease
* No second malignancies other than non-melanoma skin cancers or cervical carcinoma in situ; however, patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for \>= 3 years
* No active infection requiring treatment with antibiotics
* Patients must be able to swallow and retain oral medication
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Patients must be able to read and comprehend English or Spanish
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (1.5 x 10\^9/L)
* Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L)
* Creatinine clearance \>= 30 ml/min calculated using the Cockcroft-Gault formula
* Total serum bilirubin =\< 1.5 upper limit of normal (ULN) (\< 3 ULN if Gilbert's disease)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5.0 x ULN if liver metastases present)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if bone or liver metastases present)
* Documentation of disease: estrogen receptor positive and/or progesterone receptor (PR) positive, HER2 negative metastatic breast cancer; histologic confirmation is required
* Measurable disease or non-measurable disease
* Planning to begin palbociclib for metastatic disease; one prior line of endocrine therapy and/or chemotherapy for metastatic disease is allowed; patients may begin or have already begun endocrine therapy before they start palbociclib treatment, but no more than two weeks prior to registration
* No prior therapy with a CDK inhibitor
* Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade =\< 1 (except alopecia) or to baseline toxicities prior to previous therapy or surgical procedures, prior to registration
* No untreated brain metastases; patients with treated brain metastases must have completed treatment with steroids to be eligible
* No known interstitial lung disease
* No second malignancies other than non-melanoma skin cancers or cervical carcinoma in situ; however, patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for \>= 3 years
* No active infection requiring treatment with antibiotics
* Patients must be able to swallow and retain oral medication
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Patients must be able to read and comprehend English or Spanish
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (1.5 x 10\^9/L)
* Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L)
* Creatinine clearance \>= 30 ml/min calculated using the Cockcroft-Gault formula
* Total serum bilirubin =\< 1.5 upper limit of normal (ULN) (\< 3 ULN if Gilbert's disease)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5.0 x ULN if liver metastases present)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if bone or liver metastases present)
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
70 Years
NCT Id
NCT03633331
Org Class
Other
Org Full Name
Alliance for Clinical Trials in Oncology
Org Study Id
A171601
Overall Status
Unknown status
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II Trial Assessing the Tolerability of Palbociclib in Combination With Letrozole or Fulvestrant in Patients Aged 70 and Older With Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer
Primary Outcomes
Outcome Description
Defined as the proportion of patients with documentation of grade 3 - 5 toxicity (regardless of attribution using the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0 criteria). A 95% binomial confidence interval for single proportions will be constructed for the severe toxicity rate during treatment. Univariate relationships between the primary endpoint and various pre-treatment patient characteristics such as anemia, self-assessed functional status, or social support will be described via cross-tabulation and Fisher's exact testing. Exploratory logistic regression modeling, with limited generalizability due to the modest sample size, will be used to assess the relative contributions of these variables impact the likelihood of developing a severe toxicity during treatment. The strength of this association will be expressed in terms of an odds ratio and its associated 95% confidence interval.
Outcome Measure
Incidence of Adverse Events
Outcome Time Frame
6 months
Secondary Ids
Secondary Id
NCI-2017-01596
Secondary Outcomes
Outcome Description
Measured by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v. 5.0
Outcome Time Frame
Up to 1 year
Outcome Measure
Incidence of Drug Toxicities - Measured by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v. 5.0
Outcome Description
A 95% binomial confidence interval for single proportions will be constructed for the percentage of patients that had at least one dose reduction, dose hold, or hospitalization within the first year of treatment.
Outcome Time Frame
Up to 1 year
Outcome Measure
Dose Reduction, Dose Hold, and Hospitalization Reasons
Outcome Description
Distributions time to treatment failure will be estimated using Kaplan-Meier methodology. Treatment failure is defined as a severe adverse event, disease progression or patient refusal to continue assigned treatment. Any reason that treatment is discontinued to time to treatment failure and not censor patients will be included. The reason for treatment discontinuation will be captured.
Outcome Time Frame
Up to 5 years
Outcome Measure
Time to Treatment Failure (and Reason for Coming Off Study - Toxicity, Patient Preference, Progression)
Outcome Description
Patients to be included in the analysis cohort will be those patients who have taken one or more doses of the study treatment. Those patients will be considered adherent to study treatment. For each of the first 3 cycles, an estimate of the proportion of patients who meet the criteria for adherence and its corresponding 95% confidence interval will be determined.
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Palbociclib Adherence Rate
Outcome Description
The response rate is defined as the proportion of patients whose disease status met Response Evaluation Criteria in Solid Tumors (RECIST) criteria for complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 8 weeks apart. A 95% binomial confidence interval for the response rate will be constructed.
Outcome Time Frame
Up to 1 year
Outcome Measure
Response Rate as Determined by Response Evaluation Criteria in Solid Tumors (RECIST)
Outcome Description
Distributions of progression free survival (PFS) times will be estimated using Kaplan-Meier methodology.
Outcome Time Frame
From start of treatment to the first of the following disease events: local/regional/distant recurrence, invasive contralateral breast disease, second primary or death due to any cause, assessed up to 5 years
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
Distributions of overall survival (OS) times will be estimated using Kaplan-Meier methodology.
Outcome Time Frame
Up to 5 years
Outcome Measure
Overall Survival (OS)
Outcome Description
OTU is a novel composite endpoint developed by investigators of the FOCUS2 trial to assess the outcome of palliative chemotherapy. The patient will be given either an overall score of "good", "intermediate", or "poor". A 95% binomial confidence interval will be constructed for the percentage of patients that scored "good" on the OTU.
Outcome Time Frame
Up to 1 year
Outcome Measure
Overall Treatment Utility (OTU) Results
Outcome Description
Will examine variables associated with skeletal muscle loss during treatment and whether skeletal muscle loss during treatment is associated with the presence of grade 3-5 toxicity and adverse events. Sarcopenia will be treated as a binary variable using the Skeletal Muscle Index (SMI) (SMI \< 41 cm\^2/m\^2 vs. SMI \> 41 cm\^2/m\^2) and differences in grades chemotherapy toxicity and adverse events will be analyzed using two group t-tests and fisher's exact test. The number of patients with and without sarcopenia grouped by patients with or without grade 3+ Adverse Events (AE's) will be also be reported.
Outcome Time Frame
Up to 1 year
Outcome Measure
Sarcopenia Analysis
Outcome Description
European Quality of Life Five Dimension Three Level Questionnaire (EQ-5D-3L) is comprised of 5 dimensions. Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, no problems, some problems, extreme problems. The EQ-5D-3L can be converted to a single summary index. The median and range of this total score will be reported.
Outcome Time Frame
Up to 1 year
Outcome Measure
Quality of Life as Measured by the European Quality of Life Five Dimension Three Level Questionnaire (EQ-5D-3L)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
70
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jesus Anampa Mesias
Investigator Email
janampa@montefiore.org
Investigator Phone
718-920-4826 / 718-405-8505