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

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

  • ORG STUDY ID: 15-060
  • NCT ID: NCT02448771

Conditions

  • Breast Cancer Stage IV
  • Unresectable Locally Advanced Invasive Breast Cancer
  • Metastatic Invasive Breast Cancer

Interventions

DrugSynonymsArms
PalbociclibIbrancePalbociclib in Combination with Bazedoxifene
BazedoxifeneTSE-424 (IS), UNII-Q16TT9C5BK (IS), WAY 140424 (IS)Palbociclib in Combination with Bazedoxifene

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

NameTypeDescriptionInterventions
Palbociclib in Combination with BazedoxifeneExperimentalAfter 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, age ≥18 years of age. Men are excluded.

               -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical benefit rate (CR + PR + SD ≥ 24 weeks) of palbociclib and bazedoxifene in advanced HR+ /HER2- breast cancer.
Time Frame:24 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of Participants with Adverse Events
Time Frame:Baseline, until resolution or for 30 days after the subject's last study visit
Safety Issue:
Description:
Measure:Objective Response Rate
Time Frame:2 Years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 Years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 Years
Safety Issue:
Description:
Measure:Objective response for patients with ESR1 mutations
Time Frame:2 Years
Safety Issue:
Description:
Measure:Clinical benefit rate for patients with ESR1 mutations
Time Frame:2 Years
Safety Issue:
Description:
Measure:Progression free survival for patients with ESR1 mutations
Time Frame:2 Years
Safety Issue:
Description:
Measure:Overall survival for patients with ESR1 mutations
Time Frame:2 Years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Unresectable locally advanced invasive breast cancer
  • Metastatic invasive breast cancer

Last Updated

March 26, 2020