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

NCT03007979

Last updated date
Study Location
Washington University School of Medicine
Saint Louis, Missouri, 63110, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Breast Cancer, Breast Carcinoma, Cancer of Breast, Malignant Tumor of Breast
Sex
Female
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Histologically confirmed metastatic ER+ and/or PR+ and HER2- 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 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.

- At least 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- 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

- AST(SGOT)/ALT(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 m2 for patients with serum creatinine levels above institutional normal (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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Prior therapy with any CDK inhibitor.


- Currently receiving any other investigational agents.


- Currently receiving exogenous estrogen replacement (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 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.

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Breast Cancer, Breast Carcinoma, Cancer of Breast, Malignant Tumor of BreastAlternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer
NCT03007979
  1. Saint Louis, Missouri
  2. Lincoln, Nebraska
Female
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer
Official Title  ICMJE A Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Breast Carcinoma
  • Cancer of Breast
  • Malignant Tumor of Breast
Intervention  ICMJE
  • Drug: Palbociclib
    Palbociclib at a dose of 125 mg should be taken by mouth with food on a 5 days on/2 days off schedule
    Other Name: Ibrance
  • Drug: Letrozole
    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.
    Other Name: Femara
  • Drug: Fulvestrant
    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.
    Other Name: Faslodex
  • Procedure: Optional research biopsy
    Patients may consent to paired tumor biopsies at baseline and time of progression.
  • Drug: Goserelin
    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.
    Other Name: Zoladex
  • Procedure: Research blood draw

    -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
  • Procedure: Circulating tumor cell blood draw
    -Baseline, cycle 2 day 1, post 2 or 3 months of therapy (to coincide with first tumor imaging), and progression
  • Procedure: Tumor biopsy (optional)
    -Baseline and progression
Study Arms  ICMJE Experimental: Palbociclib + letrozole or + fulvestrant
  • 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
Interventions:
  • 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)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 30, 2019)
55
Original Estimated Enrollment  ICMJE
 (submitted: December 28, 2016)
35
Estimated Study Completion Date  ICMJE February 14, 2022
Actual Primary Completion Date March 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed metastatic ER+ and/or PR+ and HER2- 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 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.

  • At least 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status ? 2
  • Normal bone marrow and organ function as defined below:

    • 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
  • AST(SGOT)/ALT(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 m2 for patients with serum creatinine levels above institutional normal (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 (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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study:Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03007979
Other Study ID Numbers  ICMJE 201612098
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Cynthia X Ma, M.D., Ph.D.Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP