Clinical Trials /

A Study of Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Metastatic Breast Cancer

NCT02384239

Description:

Approximately 70 patients with HR+ advanced breast cancer will be enrolled. All patients will receive either fulvestrant (500 mg IM every 2 weeks x 3 then every four weeks) or tamoxifen (20 mg PO daily by physician choice). Pre-menopausal women must be in chemical menopause. Arm 1 will receive palbociclib 100 mg qd, days 1-21 every 28 days. Arm 2 will receive palbociclib 125 mg qd, days 1-21 every 28 days. Restaging will be performed every 8 weeks. Therapy will be continued until PD or unacceptable toxicity. Patients will be randomly allocated in a 1:1 ratio to take either 100 mg or 125 mg of palbociclib. Randomized treatment assignments will be made by permuted blocks, generated by our collaborating statistician at Dana-Farber Cancer Institute.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">Palbociclib</span> in Combination With <span class="go-doc-concept go-doc-intervention">Fulvestrant</span> or <span class="go-doc-concept go-doc-intervention">Tamoxifen</span> as Treatment for <span class="go-doc-concept go-doc-disease">Metastatic Breast Cancer</span>

Title

  • Brief Title: A Study of Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Metastatic Breast Cancer
  • Official Title: Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Hormone Receptor Positive Metastatic Breast Cancer Previously Exposed to Inhibitors of the PI3K Pathway: A Phase II Study With Pharmacodynamics Markers
  • Clinical Trial IDs

    NCT ID: NCT02384239

    ORG ID: 147522

    Trial Conditions

    Metastatic Breast Cancer

    Hormone Receptor Positive

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib Ibrance Palbociclib 100mg, Palbociclib 125mg

    Trial Purpose

    Approximately 70 patients with HR+ advanced breast cancer will be enrolled. All patients
    will receive either fulvestrant (500 mg IM every 2 weeks x 3 then every four weeks) or
    tamoxifen (20 mg PO daily by physician choice). Pre-menopausal women must be in chemical
    menopause.

    Arm 1 will receive palbociclib 100 mg qd, days 1-21 every 28 days. Arm 2 will receive
    palbociclib 125 mg qd, days 1-21 every 28 days. Restaging will be performed every 8 weeks.
    Therapy will be continued until PD or unacceptable toxicity.

    Patients will be randomly allocated in a 1:1 ratio to take either 100 mg or 125 mg of
    palbociclib. Randomized treatment assignments will be made by permuted blocks, generated by
    our collaborating statistician at Dana-Farber Cancer Institute.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Palbociclib 100mg Experimental Treatment arm palbociclib dose 100mg + fulvestrant or tamoxifen Palbociclib
    Palbociclib 125mg Experimental Treatment arm palbociclib dose 125mg + fulvestrant or tamoxifen Palbociclib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically proven diagnosis of breast cancer with evidence of
    metastatic or locally advanced disease, not amenable to resection or radiation
    therapy with curative intent.

    - Patients 18 years of age or older, Female patients should be either:

    - Postmenopausal, as defined by at least one of the following criteria:

    - Age 60 years;

    - Age <60 years and cessation of regular menses for at least 12 consecutive months with
    no alternative pathological or physiological cause;

    - Documented bilateral oophorectomy;

    - Medically confirmed ovarian failure.

    OR

    - Pre/peri-menopausal, ie, not meeting the criteria for being postmenopausal who are
    also receiving ongoing treatment with LHRH agonists (goserelin or leuprolide). The
    first injection should occur at least two weeks before study start.

    - Documentation of ER-positive and/or PR-positive tumor (1% positive stained cells)
    based on most recent tumor biopsy (unless bone-only disease,discuss with study PI if
    results are discordant) utilizing an assay consistent with local standards.

    - Documented HER2-negative tumor based on local testing on most recent tumor biopsy:
    HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by
    in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio <2 or for single
    probe assessment a HER2 copy number <4.

    - Must have received prior treatment with an mTOR or PI3K inhibitor

    - Up to 2 prior lines of chemotherapy are allowed in the metastatic setting.

    - Any number of lines of prior hormone therapy are allowed

    - Patients with clear progression on either tamoxifen or fulvestrant should receive the
    alternate agent. Patients with clear progression on both drugs are not eligible.

    - Ability to have a skin and tumor biopsy. Patients without accessible tumor for biopsy
    will be considered on a case by case basis.

    - Patients who cannot be biopsied will not be replaced (although up to 5
    ineligible/inevaluable patients can be replaced)

    - A patient without biopsy amenable tumor must be cleared by the PI of the study; up to
    10 patients without biopsy amenable tumor will be allowed in each arm of the study.

    - Patients without accessible tumor for biopsy must provide archived tumor from the
    most recent biopsy available

    - Bone marrow, hepatic, and renal function as follows:

    Adequate bone marrow function:

    - leukocytes > 2500/mL

    - absolute neutrophil count > 1,000/mL

    - platelets > 100,000/mL"

    Adequate hepatic function:

    - total bilirubin within normal institutional limits (unless Gilbert's disease with
    elevated indirect bilirubin only)

    - AST(SGOT) < 2.5 X institutional upper limit of normal

    - ALT(SGPT) < 2.5 X institutional upper limit of normal

    - Adequate renal function:

    - creatinine within normal institutional limits

    - Measurable or evaluable disease as defined by RECIST version 1.1. Tumor lesions
    previously irradiated or subjected to other loco-regional therapy will only be deemed
    measurable if progression at the treated site after completion of therapy is clearly
    documented.

    - Eastern Cooperative Oncology Group (ECOG) performance status 0-1

    - Resolution of acute toxic effects of prior therapy or surgical procedures to National
    Cancer Institute (NCI) CTCAE Grade 1 (except alopecia)

    - Ability to understand a written informed consent document, and the willingness to
    sign it

    Exclusion Criteria:

    - Prior treatment with any CDK inhibitor, and/or both fulvestrant and tamoxifen in the
    metastatic setting with clear progression.

    - Patients with advanced/metastatic, symptomatic, visceral spread, at risk of
    life-threatening complications in the short term by investigator assessment.

    - Known active uncontrolled or symptomatic central nervous system (CNS) metastases,
    carcinomatous meningitis, or leptomeningeal disease as indicated by clinical
    symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS
    metastases or cord compression are eligible if they have been definitively treated
    (eg, radiotherapy, stereotactic surgery) and are clinically stable off
    anticonvulsants and steroids for at least 4 weeks before randomization .

    - Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be
    potent CYP3A4 inducers (for examples, see the prohibited medications section), and
    drugs that are known to prolong the QT interval. See prohibited meds in appendix 5.

    - Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 2
    weeks before randomization.

    - Any other malignancy within 3 years prior to randomization, except for adequately
    treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.

    - QTc interval >480 msec (based on the mean value of the triplicate ECGs), family or
    personal history of long or short QT syndrome, Brugada syndrome or known history of
    QTc prolongation or Torsade de Pointes.

    QTc (Bazett) = QT/RR

    - Any of the following within 6 months prior to study enrollment: myocardial
    infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE Grade
    2, symptomatic congestive heart failure, or cerebrovascular accident excluding
    transient ischemic attack.

    - Impairment of gastrointestinal (GI) function or GI disease that may significantly
    alter the absorption of palbociclib, such as history of GI surgery with may result in
    intestinal blind loops and patients with clinically significant gastroparesis, short
    bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or
    diarrhea of CTCAE v4.0 Grade >1.

    - Prior hematopoietic stem cell or bone marrow transplantation.

    - Abnormalities in coagulation such as bleeding diathesis, or treatment with
    anticoagulants (that cannot be safely held for biopsy) that would preclude tumor and
    skin biopsies.

    - For fulvestrant: Ongoing anticoagulation that would preclude an IM injection

    - For tamoxifen: Documented hypercoagulable state not receiving anticoagulation

    - Known or possible hypersensitivity to palbociclib (CTCAE v4.0).

    - Known human immunodeficiency virus infection.

    - Other severe acute or chronic medical or psychiatric condition, including recent or
    active suicidal ideation or behavior, or laboratory abnormality that may increase the
    risk associated with study participation or investigational product administration or
    may interfere with the interpretation of study results and, in the judgment of the
    investigator, would make the patient inappropriate for entry into this study.

    - Participation in other studies involving investigational drug(s) (Phases 1-4) within
    2 weeks before randomization the current study.

    - Women should not become pregnant or breastfeed whilst on this study. Birth control
    methods are acceptable and will be discussed with study participants.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Tumor Progression as measured by RECIST 1.1

    Secondary Outcome Measures

    Progression-free Survival

    RB phosphorylation in skin

    RB phosphorylation in tumor

    Clinical Benefit Rate

    Number of Adverse Events

    Tumor markers of resistance

    Trial Keywords