Palbociclib in Molecularly Characterized ER-positive/HER2-negative Metastatic Breast Cancer (PYTHIA)

July 24, 2023 updated by: ETOP IBCSG Partners Foundation

A Phase II Study of Palbociclib Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast Cancer

This international, multicenter, prospective single arm Phase II biomarker discovery clinical trial with the primary objective of assessing the association of PFS with gene mutations, gene copy number aberrations and gene signatures in post-menopausal women with hormone receptor positive, HER2-negative metastatic or locally relapsed breast cancer whose disease has progressed after prior adjuvant endocrine therapy or one line systemic treatment, i.e., endocrine treatment or chemotherapy, administered for metastatic disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients will be treated with the combination of palbociclib and fulvestrant. The primary objective is to assess the association of the primary endpoint progression-free survival (PFS) with potential markers.

The trial is included in the AURORA program conducted by the Breast International Group (BIG), an international study aiming to collect and characterize biological samples, including metastatic tissue, from patients with advanced breast cancer.

The primary aim of the PYTHIA study is to discover potentially innovative biomarkers for the selection of patients to Palbociclib/Fulvestrant treatment. The strength of the trial lies in its conduct in conjunction with the AURORA study, which systematically evaluates a panel of biomarkers in tissue and blood, in a certified central lab. Stemming from this association, an abundance of molecular profiling information will become available for different biological samples. Additional molecular and functional imaging assessments performed within the context of the PYTHIA study increase its scientific merit, since it will represent a prospective, systematic effort to identify biomarkers for patient stratification, integrating several molecular profiling assessments.

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium, 2610
        • Sint-Augustinus
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-luc
      • Brussels, Belgium, 1000
        • Institut Jules Bodet
      • Edegem, Belgium, 2650
        • Antwerp University Hospital
      • Leuven, Belgium
        • UZ Leuven
      • Liège, Belgium
        • Chu Liege
      • Namur, Belgium, 5000
        • Clinique St. Elizabeth
  • Italy
      • Biella, Italy, 13879
        • Ospedali degli Infermi, S.O.C. Oncologia
      • Bolzano, Italy
        • Ospedale Centrale Bolzano, Medical Oncology
      • Genova, Italy
        • IRCCS San Martino University Hospital
      • Legnago, Italy
        • Mater Salutis Hospital AULSS 21 della Regione Veneto
      • Milano, Italy
        • Istituto Europeo Di Oncologia
      • Pavia, Italy, 27100
        • Istituti Clinici Scientifici Maugeri, Medical Oncology Unit
      • Prato, Italy
        • Azienda USL4 Prato
  • United Kingdom
      • Cardiff, United Kingdom
        • Velindre NHS Trust
      • Edinburgh, United Kingdom
        • Western General Hospital
      • Glasgow, United Kingdom
        • Beatson West of Scotland Cancer Centre
      • Swansea, United Kingdom
        • Singleton Hospital
      • Truro, United Kingdom
        • Royal Cornwall

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female gender
  • Age ≥ 18 years

  • Postmenopausal, defined as women with:

    • Prior bilateral surgical oophorectomy; or
    • Amenorrhea and age ≥ 60 years; or
    • Age < 60 years and amenorrhea for 12 or more consecutive months in the absence of alternative pathological or physiological cause and FSH and serum estradiol levels within the laboratory's reference ranges for postmenopausal women.

  • Endocrine resistant disease, defined as one of:

    • Relapse while on adjuvant endocrine therapy;
    • Relapse within 12 months after completion of adjuvant endocrine therapy;
    • Progression of disease under first line endocrine therapy for metastatic and/or loco-regionally advanced breast cancer.

Note: Patient may have received one prior chemotherapy for advanced or metastatic breast cancer.

  • ER positive tumor and HER2-negative tumor, as assessed locally
  • ECOG Performance Status 0-1.
  • Measurable or non-measurable but evaluable disease according to RECIST 1.1.
  • Written Informed Consent (IC) for screening procedures.
  • Written informed consent to participate in the AURORA program of BIG.
  • The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
  • Life expectancy >3 months.

  • Hematological status:

    • Absolute neutrophil count ≥ 1.5 × 109/L
    • Platelet count ≥ 100 × 109/L
    • Hemoglobin ≥ 9 g/dL

  • Hepatic status:

    • Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN).
    • AST and ALT ≤ 2.5 × ULN; if the patient has liver metastases, ALT and AST must be ≤ 5 × ULN.
  • Glucose in normal range, or well-controlled diabetes defined as an HbA1c level ≤ 7.5%.

  • Renal status:

    - Creatinine ≤ 1.5 ×ULN or creatinine clearance > 60 ml/min.

  • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulant.
  • Ability to swallow oral medication.

Exclusion Criteria:

  • Prior use of fulvestrant or any CDK inhibitor.
  • More than one prior line of chemotherapy for metastatic or locally relapsed disease.
  • Previous or current non-breast malignancies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
  • Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina pectoris, ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA functional classification ≥3), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
  • QTc exceeding 480msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
  • Uncontrolled electrolyte disorders that can reinforce the QT-prolonging effect of the drug (e.g., hypocalcemia, hypokalemia, hypomag¬nesemia).
  • Known history of HIV seropositivity. HIV screening is not required at baseline.
  • Uncontrolled diabetes defined as HbA1c level > 7.5%.
  • Concurrent disease or familial, sociological or geographical condition that would make the patient inappropriate for trial participation or any serious medical disorder that would interfere with the patient's safety.
  • Dementia, altered mental status, or any psychiatric condition that would prevent the understanding or rendering of Informed Consent.
  • Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant.
  • Treatment with an investigational agent in the 4 weeks before enrollment.
  • Concurrent treatment with any of the drugs not permitted
  • Adverse events (except alopecia) from previous systemic cancer therapy, radiotherapy or surgery have not recovered to CTCAE v4.0 grade 1 or resolved prior to enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental
Palbociclib plus Fulvestrant
Drug: Palbociclib
125 mg, orally, daily for 3 weeks followed by 1 week off; repeated at every 28 days cycle until progression, lack of tolerability, or patient declines further protocol treatment.
Other Names:
  • Ibrance
  • PD-0332991
Drug: Fulvestrant
500mg, intramuscularly on days 1 and 15 of cycle 1, then on day 1 (+/- 3 days) of every 28 days cycle until progression, lack of tolerability, or patient declines further protocol treatment.
Other Names:
  • Faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With and Without Progression Free Survival (PFS) Events
Time Frame: Maximum 36 months
Time from treatment initiation until documented disease progression according to RECIST 1.1 or death, whichever occurs first
Maximum 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response
Time Frame: From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.
Best overall response is based on RECIST (Response evaluation criteria in solid tumors) 1.1 criteria and is defined as best response recorded from enrollment across all time points until disease progression. Confirmation of partial response (PR) or complete response (CR) by an additional scan was not requested in this trial (rationale: initially because of randomized placebo-controlled design; subsequently because no hypothesis testing of progression-free survival, PFS, distribution relative to an historical control).
From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.
Best Overall Response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD)
Time Frame: From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.
Disease control is defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) (or non-CR/non-PD, progressive disease, in the case of non-measurable disease only) lasting for at least 24 weeks, measured from enrollment until first documentation of progressive disease
From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ETOP IBCSG Partners Foundation

Collaborators

Breast International Group

Investigators

  • Study Chair: Luca Malorni, MD PhD, USL4 Hospital of Prato, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2016

Primary Completion (Actual)

August 28, 2020

Study Completion (Actual)

December 22, 2022

Study Registration Dates

First Submitted

August 25, 2015

First Submitted That Met QC Criteria

August 27, 2015

First Posted (Estimated)

September 1, 2015

Study Record Updates

Last Update Posted (Estimated)

February 26, 2024

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IBCSG 53-14 / BIG 14-04
  • 2014-005387-15 (EudraCT Number)
  • WI198393 (Other Identifier: Pfizer number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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