Palbociclib in Molecularly Characterized ER-positive/HER2-negative Metastatic Breast Cancer (PYTHIA)
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|ClinicalTrials.gov Identifier: NCT02536742|
Recruitment Status : Unknown
Verified February 2021 by ETOP IBCSG Partners Foundation.
Recruitment status was: Active, not recruiting
First Posted : September 1, 2015
Last Update Posted : February 15, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Metastatic Breast Cancer||Drug: Palbociclib Drug: Fulvestrant||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||124 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Palbociclib Plus Fulvestrant for Pretreated Patients With ER+/HER2- Metastatic Breast Cancer|
|Actual Study Start Date :||August 30, 2016|
|Actual Primary Completion Date :||August 28, 2020|
|Estimated Study Completion Date :||December 2021|
Palbociclib plus Fulvestrant
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.
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 Name: Faslodex
- Progression Free Survival (PFS) [ Time Frame: Maximal 36 months ]Time from treatment initiation until documented disease progression according to RECIST 1.1 or death, whichever occurs first
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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.
- Absolute neutrophil count ≥ 1.5 × 109/L
- Platelet count ≥ 100 × 109/L
- Hemoglobin ≥ 9 g/dL
- 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%.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02536742
|Study Chair:||Luca Malorni, MD PhD||USL4 Hospital of Prato, Italy|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||ETOP IBCSG Partners Foundation|
|Other Study ID Numbers:||
IBCSG 53-14 / BIG 14-04
2014-005387-15 ( EudraCT Number )
WI198393 ( Other Identifier: Pfizer number )
|First Posted:||September 1, 2015 Key Record Dates|
|Last Update Posted:||February 15, 2021|
|Last Verified:||February 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms by Site
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action