Clinical Trials /

Palbociclib and Letrozole or Fulvestrant in Treating Patients With Estrogen Receptor Positive, HER2 Negative Metastatic Breast Cancer

NCT03633331

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib and Letrozole or Fulvestrant in Treating Patients With Estrogen Receptor Positive, HER2 Negative Metastatic Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: A171601
  • SECONDARY ID: NCI-2017-01596
  • NCT ID: NCT03633331

Conditions

  • Estrogen Receptor-positive Breast Cancer
  • HER2/Neu Negative
  • Stage IV Breast Cancer AJCC v6 and v7

Interventions

DrugSynonymsArms
PalbociclibTreatment (palbociclib, letrozole or fulvestrant)
LetrozoleTreatment (palbociclib, letrozole or fulvestrant)
FulvestrantTreatment (palbociclib, letrozole or fulvestrant)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (palbociclib, letrozole or fulvestrant)ExperimentalPatients receive palbociclib PO QD on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant IM on days 1 and 15 of course 1 and on day 1 of subsequent courses per MD discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Palbociclib
  • Letrozole
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          -  Documentation of disease: estrogen receptor positive, HER2 negative metastatic breast
             cancer; histologic confirmation is required

          -  Measurable disease or non-measurable disease

          -  Planning to begin endocrine therapy for metastatic disease; one prior line of
             endocrine therapy or chemotherapy for metastatic disease is allowed

          -  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) prior to registration

          -  No untreated brain metastases; patients with treated brain metastases must have
             completed treatment with steroids to be eligible

          -  No second malignancies other than non-melanoma skin cancers or cervical carcinoma in
             situ

          -  No active infection requiring treatment with antibiotics

          -  Patients must be able to swallow and retain oral medication

          -  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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 1 year
Safety Issue:
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.

Secondary Outcome Measures

Measure:Incidence of drug toxicities - Measured by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v. 5.0
Time Frame:Up to 1 year
Safety Issue:
Description:Measured by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v. 5.0
Measure:Dose reduction, dose hold, and hospitalization reasons
Time Frame:Up to 1 year
Safety Issue:
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.
Measure:Time to treatment failure (and reason for coming off study - toxicity, patient preference, progression)
Time Frame:Up to 5 years
Safety Issue:
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.
Measure:Palbociclib adherence rate
Time Frame:Up to 12 weeks
Safety Issue:
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.
Measure:Response rate as determined by Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame:Up to 1 year
Safety Issue:
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.
Measure:Progression free survival (PFS)
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
Safety Issue:
Description:Distributions of progression free survival (PFS) times will be estimated using Kaplan-Meier methodology.
Measure:Overall survival (OS)
Time Frame:Up to 5 years
Safety Issue:
Description:Distributions of overall survival (OS) times will be estimated using Kaplan-Meier methodology.
Measure:Overall Treatment Utility (OTU) results
Time Frame:Up to 1 year
Safety Issue:
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.
Measure:Sarcopenia analysis
Time Frame:Up to 1 year
Safety Issue:
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.
Measure:Quality of life as measured by the European Quality of Life Five Dimension Three Level Questionnaire (EQ-5D-3L)
Time Frame:Up to 1 year
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance for Clinical Trials in Oncology

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