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Breast CancerPhase 2NCT03007979

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

A Phase 2 study testing Palbociclib, Letrozole and Fulvestrant in people with Breast Cancer and Breast Carcinoma, run by Washington University School of Medicine at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer, Breast Carcinoma, Cancer of Breast
What is being tested?
Palbociclib, Letrozole and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
2 sitesUnited States
Study dates
15 Jun 2017to 31 Mar 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Nebraska

    Lincoln, Nebraska, 68588

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

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.

Being tested
Palbociclib, Letrozole, Fulvestrant, Optional research biopsy, Goserelin
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalbociclibDrug

    Also called Ibrance

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

  • LetrozoleDrug

    Also called Femara

    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.

  • FulvestrantDrug

    Also called Faslodex

    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.

  • Optional research biopsyProcedure or surgery

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

  • GoserelinDrug

    Also called Zoladex

    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.

  • Research blood drawProcedure or surgery

    -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

  • Circulating tumor cell blood drawProcedure or surgery

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

  • Tumor biopsy (optional)Procedure or surgery

    -Baseline and progression

Study groups in NCT03007979
Study groupRoleWhat they receive
Palbociclib + letrozole or + fulvestrantExperimental* 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
Receives: 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)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Through the first 29 days of treatment

Secondary outcomes (8)

  1. 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

    Measured: Through 30 day follow-up (estimated to be 25 months)

  2. Rate of Palbociclib Dose Reduction

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

    Measured: Through the completion of treatment (estimated to be 24 months)

  3. Rate of Palbociclib Dose Interruption

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

    Measured: Through the completion of treatment (estimated to be 24 months)

  4. Rate of Palbociclib Discontinuation

    -Percentage of participants who discontinue palbociclib due to adverse event

    Measured: Through the completion of treatment (estimated to be 24 months)

  5. 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.

    Measured: Through the 30 day follow-up (estimated to be 25 months)

  6. 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).

    Measured: 1 year

  7. 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

    Measured: Time of progression (estimated to be 24 months)

  8. 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.

    Measured: Time of progression (estimated to be 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2017 (estimated)
  2. Study start15 Jun 2017
  3. Primary completion13 Mar 2020
  4. Study completion31 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03007979
Sponsor's protocol ID
201612098
Status last verified
Feb 2024
First submitted
19 Dec 2016
Last updated
20 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Krishnamurthy J, Luo J, Suresh R, Ademuyiwa F, Rigden C, Rearden T, Clifton K, Weilbaecher K, Frith A, Roshal A, Tandra PK, Cherian M, Summa T, Haas B, Thomas S, Hernandez-Aya L, Bergqvist M, Peterson L, Ma CX. A phase II trial of an alternative schedule of palbociclib and embedded serum TK1 analysis. NPJ Breast Cancer. 2022 Mar 21;8(1):35. doi: 10.1038/s41523-022-00399-w.

    PubMed 35314693

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palbociclib, Letrozole and Fulvestrant in people with Breast Cancer and Breast Carcinoma, run by Washington University School of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Grade 3 or Higher Neutropenia (time frame: Through the first 29 days of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03007979, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.

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