Clinical Trials /

A Study of Palbociclib in Combination With Bazedoxifene in Hormone Receptor Positive Breast Cancer

NCT02448771

Description:

This research study is studying a drug called Palbociclib in combination with Bazedoxifene (a type of endocrine therapy, which prevents breast cancer cell growth by blocking estrogen stimulation) as a possible treatment for this diagnosis. The names of the study interventions involved in this study are: - Palbociclib - Bazedoxifene

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/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">Bazedoxifene</span> in Hormone Receptor Positive <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: A Study of Palbociclib in Combination With Bazedoxifene in Hormone Receptor Positive Breast Cancer
  • Official Title: A Phase Ib/II Study of Palbociclib in Combination With Bazedoxifene in Hormone Receptor Positive Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02448771

    ORG ID: 15-060

    Trial Conditions

    Breast Cancer Stage IV

    Unresectable Locally Advanced Invasive Breast Cancer

    Metastatic Invasive Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib Ibrance Palbociclib in Combination with Bazedoxifene
    Bazedoxifene TSE-424 (IS), UNII-Q16TT9C5BK (IS), WAY 140424 (IS) Palbociclib in Combination with Bazedoxifene

    Trial Purpose

    This research study is studying a drug called Palbociclib in combination with Bazedoxifene
    (a type of endocrine therapy, which prevents breast cancer cell growth by blocking estrogen
    stimulation) as a possible treatment for this diagnosis.

    The names of the study interventions involved in this study are:

    - Palbociclib

    - Bazedoxifene

    Detailed Description

    This research study is a Phase I/II clinical trial. Phase II clinical trial tests the
    safety and effectiveness of an investigational intervention to learn whether the
    intervention works in treating a specific disease. "Investigational" means that the
    intervention is being studied. It also means that the FDA (the U.S. Food and Drug
    Administration) has not yet approved Palbociclib in combination with Bazedoxifene for use in
    participants with your type of cancer, but it has been approved for other uses (metastatic
    breast cancer).

    Palbociclib is a drug that may stop cancer cells from growing. Palbociclib blocks activity
    of two closely related enzymes (proteins that help chemical reactions in the body occur),
    called Cyclin D Kinases 4 and 6 (CDK 4/6). These proteins are part of a pathway, or a
    sequence of steps which is known to control cell growth. Laboratory testing has shown that
    palbociclib may stop the growth of hormone receptor positive breast cancer.

    Endocrine therapy prevents breast cancer cell growth by blocking the activity of the
    estrogen receptor. During this study the endocrine therapy will be bazedoxifene.

    In this research study, the investigators are evaluating how safe palbociclib is and how
    well palbociclib in combination with bazedoxifene, a form of endocrine treatment, works in
    participants with a history of stage four breast cancer.

    Trial Arms

    Name Type Description Interventions
    Palbociclib in Combination with Bazedoxifene Experimental After the screening procedures confirm eligibility participate in the research study. Palbociclib Oral, predetermined time per cycle, predetermined dosage per protocol. Bazedoxifene Oral, daily per cycle, predetermined dosage per protocol. Palbociclib, Bazedoxifene

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must have histologically confirmed invasive breast cancer that is
    metastatic or unresectable locally advanced. Histological documentation of
    metastatic/recurrent breast cancer is not required if there is unequivocal evidence
    for recurrence of the breast cancer.

    - Estrogen and/or progesterone receptor positive breast cancer (>10% staining), as
    determined by pathology from either primary or metastatic site(s). Central
    confirmation is not required.

    - HER2 negative, defined as 0-1+ by immunohistochemistry or FISH-negative (HER2 copy
    number <6 and HER2/CEP17 ratio < 2.0). Central confirmation is not required.

    - Postmenopausal women are eligible. Postmenopausal is defined as any of the following:

    - Age 60 years

    - Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy,
    tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the
    postmenopausal range per local normal range.

    - Premenopausal women who have been on a GnRH agonist for at least 3 consecutive
    months prior to study entry are eligible. Women in this group MUST remain on the
    GnRH agonist for the duration of protocol treatment.

    - Status-post bilateral oophorectomy-After adequate healing post surgery.

    - Women and men, age 18 years of age

    -- Because no dosing or adverse event data are currently available on the use of
    palbociclib and bazedoxifene in participants <18 years of age, children are excluded
    from this study. In addition, breast cancer is exceedingly rare in individuals under
    18 years of age.

    - Participants must have measurable disease by RECIST 1.1. See section 11 for the
    definition of measurable disease.

    - Bone only disease if there are lytic lesions is also allowed and treatment response
    will be evaluated based on the MD Anderson criteria. See section 11.

    - Endocrine resistant breast cancer, defined as either:

    - Relapsed while on adjuvant endocrine therapy or within 1 year of completion of
    adjuvant endocrine therapy

    --- -or-

    - Progression through at least one line of endocrine therapy for metastatic or
    locally advanced breast cancer. There is no limit on the number of prior
    endocrine therapies received.

    - Patients may have received up to one prior line of chemotherapy for metastatic
    or unresectable locally advanced breast cancer.

    - Patients may have initiated bisphosphonate therapy prior to start of protocol
    therapy. Bisphosphonate therapy may continue during protocol treatment. Such
    patients will have bone lesions considered evaluable for progression

    - Patients must be at least 2 weeks from prior chemotherapy or radiotherapy, or
    any investigational drug product, with adequate recovery of toxicity to
    baseline, or grade <1, with the exception of alopecia and hot flashes. There is
    no washout period for prior endocrine therapy.

    - ECOG Performance Status 0-1 (Appendix A)

    - Life expectancy of greater than 3 months

    - Willingness to undergo research biopsy under the following circumstances:

    - Patients with "easily accessible disease"

    - Patients with skin or chest wall disease amenable to a punch biopsy under
    local anesthesia are required to undergo a baseline biopsy and a biopsy at
    the time of disease progression as part of this protocol.

    - Patients with a breast mass or axillary lymph node amenable to an
    image-guided core biopsy are also required to undergo a baseline biopsy and
    a biopsy at the time of disease progression as part of this protocol.

    - Patients with malignant ascites fluid or a malignant pleural effusion of
    sufficient volume to be amenable to tap (either in-office or image-guided)
    are also required to undergo a baseline tap and a tap at the time of
    disease progression as part of this protocol.

    - Patients who undergo a research biopsy procedure for the purpose of this
    protocol, and in whom inadequate tissue is obtained, are still eligible and
    are not required to undergo a repeat biopsy in order to enter the study.

    - Patients will be approached during cycle 1 about providing an optional
    tissue sample at that time; however, this biopsy will be optional.

    - Patients with "accessible disease"

    - Patients with sites felt to be accessible to an image-guided or incisional
    biopsy in the opinion of the patient's treating oncologist and physician
    performing the procedure, and not meeting the criteria for "easily
    accessible disease" as described in Section 3.1.14.1, are required to
    undergo a baseline biopsy as part of this protocol. Such sites may include,
    but are not limited to: liver, lymph nodes, soft tissue, lung, chest wall,
    and bone. Cycle 1 biopsy and biopsy at time of disease progression are
    optional.

    - Biopsies may be done with local anesthesia or intravenous conscious
    sedation, according to standard institutional guidelines.

    - If a biopsy requires general anesthesia, then it is only allowed if
    acquisition of tissue is necessary for clinical reasons (i.e. is clinically
    indicated), and excess tissue that would otherwise have been discarded is
    then used for research purposes. If a biopsy requires general anesthesia,
    then a biopsy of that site for research purposes only, without a coexisting
    clinical indication is not allowed on this protocol.

    - Patients who undergo a research biopsy procedure for the purpose of this
    protocol, and in whom inadequate tissue is obtained, are still eligible and
    are not required to undergo a repeat biopsy in order to enter the study.

    - Some patients may have had a clinically indicated biopsy upon recent
    disease progression. No additional pre-treatment biopsy is required if that
    specimen can be used for the correlative studies described in this
    protocol.

    - Patients will be approached at the time of progression about providing an
    optional tissue sample at that time; however, the time of progression
    biopsy will be optional.

    - Other patients

    - Patients who do not have biopsy-accessible disease are not required to
    undergo a biopsy as part of study participation.

    - In addition, patients who are being treated with therapeutic doses of
    anticoagulant(s), are not required to undergo a biopsy as part of study
    participation. If it is felt clinically appropriate despite anticoagulation
    (i.e. a skin punch biopsy, etc) by the treating physician, a biopsy is
    allowed, it is simply not required.

    - The sites of metastatic disease and reason that the disease is not
    biopsy-accessible should be documented in the medical record and case
    report form(s).

    - Patients who do not undergo baseline biopsy must have their study
    participation approved by the overall PI before start of protocol therapy.
    Only patients who have biopsy inaccessible disease may enter the study
    without the requirement for baseline biopsy.

    - Participants must have normal organ and marrow function as defined below:

    - Absolute neutrophil count 1,500/mcL

    - Platelets 100,000/mcL

    - Hgb 9 mg/dL (which may be post transfusion)

    - Total bilirubin 1.5 X institutional upper limit of normal (patients with

    ---- documented Gilbert's disease are allowed total bilirubin up to 3X ULN)

    - AST (SGOT)/ALT (SGPT) 2.5 X institutional upper limit if no liver metastases;
    and 5 X institutional upper limit if liver metastases are present.

    - Creatinine 2X institutional upper limit of normal

    - Baseline QTc 480 ms

    - Ability to take oral medications.

    - The effects of palbociclib and bazedoxifene on the developing human fetus are
    unknown. If, for any reason, a woman should become pregnant or suspect that she is
    pregnant while participating in this study, she should inform her treating physician
    immediately.

    - Women who are made postmenopausal through use of GNRH agonists, and men are required
    to use adequate contraception for the duration of protocol treatment and for 6 months
    after the last dose of palbociclib and bazedoxifene. Adequate contraception is
    defined as one highly effective non-hormonal form of contraception or two effective
    forms of non-hormonal contraception by the patient and/or partner.

    - Highly Effective Non-Hormonal Contraception Methods of birth control which result in
    a low failure rate (i.e., less than 1% per year) when used consistently and correctly
    are considered highly-effective forms of contraception. The following non-hormonal
    methods of contraception are acceptable:

    - True abstinence when this is in line with the preferred and usual lifestyle of
    the patient. [Periodic abstinence (e.g., calendar, ovulation, symptothermal
    post-ovulation methods) and withdrawal are not acceptable methods of
    contraception].

    - Male sterilization (with appropriate post-vasectomy documentation of the absence
    of sperm in the ejaculate). For female patients, the vasectomized male partner
    should be the sole partner.

    --- OR

    - Effective Non-Hormonal Contraception

    Alternatively two of the following effective forms of contraception may be used instead:

    - Placement of non-hormonal intrauterine device (IUD) or intrauterine system (IUS).
    Consideration should be given to the type of device being used, as there is higher
    failure rates quoted for certain types, e.g., steel or copper wire.

    - Condom with spermicidal foam/gel/film/cream/suppository.

    - Occlusive cap (diaphragm or cervical/vault caps) with spermicidal
    foam/gel/film/cream/suppository. The use of barrier contraceptives should always be
    supplemented with the use of spermicide.

    - The following should be noted:

    - Failure rates indicate that, when used alone, the diaphragm and ondom are not highly
    effective forms of contraception. Therefore, the use of additional spermicides does
    confer additional theoretical contraceptive protection.

    - However, spermicides alone are ineffective at preventing pregnancy when the whole
    ejaculate is spilled. Therefore, spermicides are not a barrier method of
    contraception and should not be used alone.

    - It should be noted that two forms of effective contraception are required. A
    double barrier method is acceptable, which is defined as condom and occlusive
    cap (diaphragm or cervical/ vault caps) with spermicidal foam/gel/film/cream
    /suppository. Premenopausal women who have been on a GnRH agonist for at least 3
    consecutive months prior to study entry are eligible. Women in this group MUST
    remain on the GnRH agonist for the duration of protocol treatment. Such patients
    should be counseled that GnRH agonists alone may not be adequate contraception
    and that adequate contraception (hormonal or barrier method of birth control;
    abstinence) prior to study entry and for the duration of study participation
    should be employed.

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

    Exclusion Criteria:

    - Prior treatment with a CDK4/6 inhibitor and/or bazedoxifene.

    - Participants may not be receiving any other investigational agents.

    - Concurrent treatment with commercial agents or other agents with the intent to treat
    the participant's malignancy, including endocrine therapy, chemotherapy, and/or
    targeted therapy, with the exception of bisphosphonates and GnRH agonists, as
    detailed in sections 3.1.4 and 3.1.9.

    - Untreated or progressive brain metastases. Patients with treated brain metastases not
    requiring chronic corticosteroids for symptom control are eligible.

    - Pending visceral crisis, in the opinion of the treating investigator.

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to palbociclib and /or bazedoxifene.

    - Participants receiving any medications or substances that are strong inhibitors or
    inducers of CYP3A isoenzymes are ineligible. Lists including medications and
    substances known or with the potential to interact with the CYP3A isoenzymes are
    provided in Appendix D. Because the lists of these agents are constantly changing, it
    is important to regularly consult a frequently-updated list such as
    http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as
    the Physicians' Desk Reference may also provide this information. As part of the
    enrollment/informed consent procedures, the patient will be counseled on the risk of
    interactions with other agents, and what to do if new medications need to be
    prescribed or if the patient is considering a new over-the-counter medicine or herbal
    product.

    - Current use of drugs that are known to prolong the QT interval (See Appendix C)

    - Subjects with organ allograft requiring immunosuppression.

    - Uncontrolled intercurrent illness including, but not limited to ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements. Ability to comply with study requirements is to be assessed by
    each investigator at the time of screening for study participation.

    - Pregnant women are excluded from this study because effects of palbociclib and
    bazedoxifene on a developing fetus is unknown. Breastfeeding should be discontinued
    prior to entry onto the study.

    - Individuals with a history of a different malignancy are ineligible except for the
    following circumstances. Individuals with a history of other malignancies are
    eligible if they have been disease-free for at least 5 years and are deemed by the
    investigator to be at low risk for recurrence of that malignancy. Individuals with
    the following cancers are eligible if diagnosed and treated within the past 5 years:
    ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or
    squamous cell carcinoma of the skin.

    - Patients on combination antiretroviral therapy, i.e. those who are HIV-positive, are
    ineligible because of the potential for pharmacokinetic interactions or significant
    immunosuppression with Palbociclib.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Clinical benefit rate (CR + PR + SD 24 weeks) of palbociclib and bazedoxifene in advanced HR+ /HER2- breast cancer.

    Secondary Outcome Measures

    Number of Participants with Adverse Events

    Objective Response Rate

    Progression Free Survival

    Overall Survival

    Objective response for patients with ESR1 mutations

    Clinical benefit rate for patients with ESR1 mutations

    Progression free survival for patients with ESR1 mutations

    Overall survival for patients with ESR1 mutations

    Trial Keywords

    Unresectable locally advanced invasive breast cancer

    Metastatic invasive breast cancer