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CDK4/6 Inhibitor

Genetically-informed Therapy for Advanced Breast Cancer (GERTRUDE Trial)

Phase 2
Recruiting
Led By Mary Chamberlin, MD
Research Sponsored by Dartmouth-Hitchcock Medical Center
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Post-menopausal women ≥18 years of age with metastatic ER+ breast cancer, or with locally recurrent ER+ disease not amenable to therapy for curative intent
Patient must have been treated with a CDK4/6i (either palbociclib, ribociclib, or abemaciclib) alone or in combination with an endocrine agent in the advanced disease setting
Must not have
Treatment with abemaciclib in the most recent or current line of therapy
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 6 - 12 months
Awards & highlights

Summary

This trial looks to see if certain drug combos can help people with advanced breast cancer who have tried 3 drugs already.

Who is the study for?
This trial is for post-menopausal women aged 18 or older with advanced ER+/HER2- breast cancer, who have been treated with CDK4/6 inhibitors like palbociclib. They can have up to three prior therapies after the inhibitor and one line of chemotherapy. Participants must not be currently on abemaciclib or any investigational cancer therapy within the last three weeks.Check my eligibility
What is being tested?
The study tests combinations of drugs (Abemaciclib, Fulvestrant, Neratinib, Alpelisib, Everolimus) in patients previously treated with CDK4/6 inhibitors. It aims to find effective treatments based on genetic profiles that include specific alterations relevant to the study.See study design
What are the potential side effects?
Potential side effects may include gastrointestinal issues such as diarrhea and nausea; skin reactions; blood clots; fatigue; decreased appetite; changes in liver function tests; and potential risk of infections due to lowered white blood cell counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I am a post-menopausal woman over 18 with advanced ER+ breast cancer not treatable for a cure.
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I have been treated with a CDK4/6 inhibitor for advanced cancer.
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My tumor or blood sample was tested for specific genes in a certified lab after my cancer progressed.
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My cancer is estrogen receptor positive.
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My breast cancer is estrogen receptor positive, confirmed by a biopsy.
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I've had a PET/CT scan or a CT scan with contrast and a bone scan.
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I am post-menopausal according to NCCN guidelines.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I am currently being treated with abemaciclib.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~6 - 12 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 - 12 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor.
Secondary outcome measures
Incidence rate of adverse events within each treatment arm.
Progression-free survival within each treatment arm.
Rate of objective response within each treatment arm.

Trial Design

4Treatment groups
Experimental Treatment
Group I: Arm D- abemaciclib and fulvestrantExperimental Treatment2 Interventions
If a participant does not have a qualifying mutation/alteration for Arms A/B/C, and the participant does not have mutation or loss of RB1, the subject will be assigned to Treatment Arm D and given the combination of abemaciclib and fulvestrant until the end of the primary treatment phase. Fulvestrant (500 mg) will be administered by intramuscular injection into the buttocks on Cycle 1 Day 1 and Day 15, and on Day 1 of subsequent Cycles. Abemaciclib will be administered orally in 1 tablet (150 mg) taken 2 times per day, in combination with fulvestrant as described above.
Group II: Arm C- everolimus and fulvestrantExperimental Treatment2 Interventions
If a subject does not have a qualifying ERBB2 or PIK3CA mutation, but they have a qualifying mutation/alteration in AKT1, MTOR, or PTEN, the subject will be assigned to Treatment Arm C and given the combination of everolimus and fulvestrant until the end of the primary treatment phase. Fulvestrant (500 mg) will be administered by intramuscular injection into the buttocks on Cycle 1 Day 1 and Day 15, and on Day 1 of subsequent Cycles. Everolimus will be administered orally in 1 tablet (10 mg per tablet) taken 1 time per day, in combination with fulvestrant as described above.
Group III: Arm B- alpelisib and fulvestrantExperimental Treatment2 Interventions
If a participant does not have a qualifying ERBB2 (HER2) mutation, but they have a qualifying PIK3CA mutation, the subject will be assigned to Treatment Arm B and given the combination of alpelisib and fulvestrant until the end of the primary treatment phase. Fulvestrant (500 mg) will be administered by intramuscular injection into the buttocks on Cycle 1 Day 1 and Day 15, and on Day 1 of subsequent Cycles. Alpelisib will be administered orally in 2 tablets (total dose of 300 mg) taken 1 time per day with food, in combination with fulvestrant as described above.
Group IV: Arm A- neratinib and fulvestrantExperimental Treatment2 Interventions
Participants with a qualifying ERBB2 (HER2) mutation will be assigned to Treatment Arm A and given the combination of neratinib and fulvestrant until the end of the primary treatment phase. Fulvestrant (500 mg) will be administered by intramuscular injection into the buttocks on Cycle 1 Day 1 and Day 15, and on Day 1 of subsequent Cycles. Neratinib will initially be administered orally in 3 tablets (total dose of 120 mg) taken 1 time per day with food on Cycle 1 Days 1-7, in combination with fulvestrant starting on Cycle 1 Day 1 as described above. The dose of neratinib will be increased to 4 tablets (total dose of 160 mg) taken 1 time per day with food on Cycle 1 Days 8-14, and then increased further to 6 tablets (240 mg) taken once daily with food thereafter.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Abemaciclib
2019
Completed Phase 2
~1800
Fulvestrant
2011
Completed Phase 3
~3810
Neratinib
2014
Completed Phase 2
~1970
Alpelisib
2018
Completed Phase 3
~900
Everolimus
2010
Completed Phase 4
~1510

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Common treatments for breast cancer include endocrine therapy and targeted therapy. Endocrine therapy blocks hormones like estrogen that fuel hormone receptor-positive breast cancer, using agents such as tamoxifen, letrozole, and fulvestrant. Targeted therapies, including PI3K and mTOR inhibitors, disrupt specific molecular pathways crucial for cancer cell growth and survival. PI3K inhibitors target the PI3K/AKT/mTOR pathway, while mTOR inhibitors directly inhibit the mTOR protein. Combining these therapies can enhance treatment efficacy, overcome resistance, and improve progression-free survival in advanced breast cancer patients.
A new era of improving progression-free survival with dual blockade in postmenopausal HR(+), HER2(-) advanced breast cancer.A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative.Endocrine and targeted manipulation of breast cancer: summary statement for the Sixth Cambridge Conference.

Find a Location

Who is running the clinical trial?

Dartmouth-Hitchcock Medical CenterLead Sponsor
530 Previous Clinical Trials
2,544,799 Total Patients Enrolled
29 Trials studying Breast Cancer
2,352,939 Patients Enrolled for Breast Cancer
Mary Chamberlin, MDPrincipal InvestigatorDartmouth-Hitchcock Medical Center
5 Previous Clinical Trials
93 Total Patients Enrolled

Media Library

Abemaciclib (CDK4/6 Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT05933395 — Phase 2
Breast Cancer Research Study Groups: Arm B- alpelisib and fulvestrant, Arm A- neratinib and fulvestrant, Arm C- everolimus and fulvestrant, Arm D- abemaciclib and fulvestrant
Breast Cancer Clinical Trial 2023: Abemaciclib Highlights & Side Effects. Trial Name: NCT05933395 — Phase 2
Abemaciclib (CDK4/6 Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05933395 — Phase 2
~90 spots leftby Oct 2030