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

NCT02448771 | Completed Phase 1 Results DMC

• 1 other identifier: 15-060
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

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

Keywords

Unresectable locally advanced invasive breast cancer; Metastatic invasive breast cancer

Outcome Measures

Primary Outcomes (3)

• Clinical Benefit Rate

  Clinical Benefit Rate is the percentage of participants who achieve clinical benefit from the study treatment. Clinical benefit is defined as at least 24 weeks of confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD). SD or better is achieved if the following are true: Target Lesions: -At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Non-target Lesions: * No progression. * No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Bone Lesions: * \< 25% increase in lesions. * No new lesions.

  Assessed for response for up to 34 months

• Clinical Benefit Rate by ESR1 Genotype

  Clinical Benefit Rate is the percentage of participants who achieve clinical benefit from the study treatment. Clinical benefit is defined as at least 24 weeks of confirmed CR, PR, SD. SD or better is achieved if the following are true: Target Lesions: -At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Non-target Lesions: * No progression. * No appearance new lesions or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Bone Lesions: * \< 25% increase in lesions. * No new lesions. ESR1 genotype determined using established methods

  Assessed for response for up to 34 months

• Percent of Participants With All Grade Neutrophil Count Decrease

  Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 regardless of whether the event is related or unrelated to treatment. Neutrophil counts are evaluated using established methods.

  Baseline, until resolution or for 30 days after the subject's last study visit, up to 43 months.

Secondary Outcomes (7)

• Number of Participants With All Grade Neutrophil Count Decrease

  Baseline, until resolution or for 30 days after the subject's last study visit, up to 43 months.

• Objective Response Rate

  Assessed for response for up to 34 months

• Median Progression-Free Survival

  Up to 42 months

• Median Overall Survival

  Up to 42 months

• Median Progression-Free Survival for Patients by ESR1 Genotype

  Up to 24 months

Study Arms (1)

Palbociclib in Combination with Bazedoxifene

EXPERIMENTAL

Palbociclib 125 mg Oral on days 1-21 per cycle Bazedoxifene 40 mg Oral on days 1-28 per cycle One cycle is 28 days.

Drug: Palbociclib; Drug: Bazedoxifene

Interventions

Palbociclib DRUG

Also known as: Ibrance

Palbociclib in Combination with Bazedoxifene

Bazedoxifene DRUG

Also known as: TSE-424 (IS), UNII-Q16TT9C5BK (IS), WAY 140424 (IS)

Palbociclib in Combination with Bazedoxifene

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C, Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, McDonnell DP, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clin Cancer Res. 2022 Dec 1;28(23):5066-5078. doi: 10.1158/1078-0432.CCR-22-2305.

  PMID: 36215125 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; bazedoxifene

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Rinath Jeselsohn
• Organization: Dana-Farber Cancer Institute

rinath_jeselsohn@dfci.harvard.edu

617.632.6887

Study Officials

• Rinath Jelsohn, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 4, 2015
• First Posted: May 19, 2015
• Study Start: July 9, 2015
• Primary Completion: August 12, 2019
• Study Completion: March 3, 2021
• Last Updated: October 24, 2022
• Results First Posted: July 1, 2021

Record last verified: 2022-10

Locations

US (2)