Palbociclib With Everolimus + Exemestane In BC

NCT02871791 | Completed Phase 1 Results DMC

• 1 other identifier: 16-177
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of targeted therapy and hormonal therapy as a possible treatment for breast cancer that has spread to other places in the body and is hormone receptor positive (HR+) and HER2-negative. The names of the study interventions involved in this study are:

• Palbociclib
• Everolimus
• Exemestane

Conditions

Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Hormone Receptor (HR)-Positive Breast Cancer

Keywords

Her2-negative metastatic breast cancer; Hormone receptor (HR)-positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR) [Phase 2a]

  CBR is defined as the proportion of participants achieving complete response, partial response or stable disease for more than 6 months (CR+PR+SD ≥ 24 weeks) taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.

  Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.

Secondary Outcomes (4)

• Overall Response Rate (ORR) [Phase 2a]

  Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.

• Disease Control Rate (DCR) [Phase 2a]

  Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.

• Duration of Response (DOR) [Phase 2a]

  Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.

• Median Progression Free Survival (PFS) [Phase 2a]

  Disease is evaluated and followed-up every 8 weeks, with median of 20.04 months and maximum of 35.64 months.

Study Arms (1)

Palbociclib, Everolimus, Exemestane

EXPERIMENTAL

* Palbociclib will be administered orally, 100mg, once daily for 21 consecutive days followed by a 7-day rest (28-day cycle) * Everolimus will be administered orally, 5mg, once daily on a 28 day schedule * Exemestane will be administered orally, 25mg, once daily on a 28 day schedule

Drug: Palbociclib; Drug: Everolimus; Drug: Exemestane

Interventions

Palbociclib DRUG

Palbociclib, Everolimus, Exemestane

Everolimus DRUG

Palbociclib, Everolimus, Exemestane

Exemestane DRUG

Palbociclib, Everolimus, Exemestane

Eligibility Criteria

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

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study. Laboratory tests required for eligibility must be completed within 14 days prior to the date of registration. Diagnostic tests, such as MRIs and CT scans, must be performed within 30 days of registration and baseline measurements must be documented within 14 days of the date of registration.
• Participants with histologically or cytologically confirmed hormone receptor (HR)-positive, Her2-negative metastatic breast cancer. Central confirmation of HR positivity is not required
• Postmenopausal women as defined as:
• Age \>60 years
• \--- or
• Age \>45 with intact uterus and amenorrhea for ≥ 12 consecutive months or Follicle stimulating hormone (FSH) levels within postmenopausal range according to the ranges established by the testing facility
• \--- or
• Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry. Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment
• \--- or
• Status post bilateral oophorectomy, after adequate healing post surgery;
• Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry. Men MUST remain on the GnRH agonist for the duration of protocol treatment.
• Participants must have measurable disease as per RECIST 1.1.
• Prior Treatment Specifics:
• Participants must have radiological or objective evidence of progression to a CDK4/6 inhibitor regimen in the metastatic setting AND relapse/progression on an NSAI (defined as either relapsed ≤ 12 months after completing adjuvant NSAI or progressed through an NSAI for metastatic or locally advanced breast cancer)
• Participants may have received any number of previous endocrine/hormonal lines of therapy in the metastatic setting, as long none of them were exemestane-based and the last dose is ≥ 14 days prior to registration;

You may not qualify if:

• Participants who have demonstrated intolerance to 125mg of Palbociclib are ineligible for the Phase I portion.
• Participants who are receiving any other investigational agents.
• Participants who have received previous treatment with an mTOR inhibitor or exemestane.
• Participants with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib, everolimus or exemestane.
• Participants with known brain metastases may be enrolled in this study if radiation therapy and/or surgery have been completed with a minimum of 3 months of stable disease demonstrated on serial evaluation by CT (with contrast enhancement) or MRI. Such participants must no longer require treatment with corticosteroids or enzyme inducing anti-epileptic medications for their CNS disease.
• Participants with bilateral diffuse lymphangitic carcinomatosis.
• Participants with significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
• Evidence of current pneumonitis
• Subjects with organ allograft requiring immunosuppression.
• Participants with uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic 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;
• Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome).
• Participants receiving any medications or substances that are moderate or strong inhibitors or inducers of CYP3A within 7 days of registration. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in Appendix B, and can also be found within Sections 2.4.1.2 and 5.8. 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 participant 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 participant is considering a new over-the-counter medicine or herbal product.
• Proton pump inhibitors(PPI) may be taken while on study, however it is recommended that the PPI is taken 12 hours from the time of palbociclib administration. If needed, alternative antacid therapies may be used including H2-receptor antagonists and locally acting antacids. H2-receptor antagonists should be administered with a staggered dosing regimen (twice daily). The dosing of palbociclib should occur at least 10 hours after H2-receptor antagonist evening dose and 2 hours before the H2-receptor antagonist morning dose.
• Pregnant women are excluded.

Sponsors & Collaborators

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

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Interventions

palbociclib; Everolimus; exemestane

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Sara Tolaney, MD MPH
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617-632-5743

Study Officials

• Sara Tolaney, 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: June 29, 2016
• First Posted: August 18, 2016
• Study Start: August 24, 2016
• Primary Completion: December 3, 2020
• Study Completion: September 1, 2021
• Last Updated: August 29, 2022
• Results First Posted: August 29, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)