Advanced Breast CancerPhase 2GERTRUDENCT05933395
Genetically-informed Therapy for ER+ Breast Cancer Post-CDK4/6 Inhibitor
A Phase 2 study testing Fulvestrant, Neratinib and Alpelisib in people with Advanced Breast Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to learn if certain drug combinations are effective treatments for patients with advanced ER+/HER2- who have previously been treated with palbociclib, ribociclib, or abemaciclib. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Breast Cancer
- What is being tested?
- Fulvestrant, Neratinib and Alpelisib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2024to Oct 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 be post-menopausal per NCCN guidelines.
- Patient must have been treated with a CDK4/6i (either palbobclib, ribociclib, or abemaciclib) alone or in combination with an endocrine agent in the advanced disease setting.
- Up to 3 lines of therapy following CDK4/6i are permissible.
- Any number of prior lines of endocrine-containing therapy is permissible.
- Up to 1 prior line of chemotherapy is permissible.
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- Histologic documentation of ER+ breast cancer by core needle biopsy, fine needle aspiration, incisional biopsy, or surgical biopsy of ≥1 site(s) of metastatic or locally recurrent disease performed as standard of care.
- Exceptions: patients with bone-dominant metastatic disease, or non-bone metastatic disease in whom a safe and accurate biopsy of recurrent/metastatic disease cannot be readily obtained, with a history of ER+ breast cancer are eligible, and biopsy is not required, providing their primary cancer is consistent with the ER criteria described below.
- ER+ status defined as ER staining by immunohistochemistry in ≥1% of malignant cell nuclei.
- Tumor must be HER2-non-amplified as defined by an immunohistochemistry score of 0-1+, or with a FISH ratio <2 if IHC is 2+ or if IHC has not been done (as per ASCO/CAP definitions). In cases of borderline or equivocal HER2 status, eligibility will be determined by the PI.
- Genetic profiling of a tumor or plasma specimen acquired after disease progression on a CDK4/6i must have been performed in a CAP-accredited, CLIA-certified laboratory using clinically validated methods. Profiling must minimally include analysis of study-relevant alterations in ERBB2, PIK3CA, AKT1, MTOR, PTEN, and RB1.
- If not done: Profiling of a tumor (preferable) or plasma specimen will be performed as part of the study in the DHMC Pathology Laboratory. A plasma specimen may be obtained for study-specific genetic profiling to direct treatment assignment. Tumor specimens must be obtained outside of this study (e.g., by biopsy).
- If available, archived tumor tissue must be accessible for research purposes, sufficient to make ≥10 five-micron sections; more tumor tissue is preferred.
- Radiographic staging performed as standard of care, including specifically either PET/CT, or contrast CT (CAP) and bone scan.
- Patient must be capable and willing to provide informed written consent for study participation.
Who cannot join
- Treatment with abemaciclib in the most recent or current line of therapy.
- During the study Treatment Phases, no concurrent anti-cancer therapies are allowed with the following exception: anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
- Any investigational cancer therapy in the last 3 weeks.
- Known untreated CNS disease, unless clinically stable for ≥ 3 months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Research Nurse, 603-650-5021, hem-onc.research.nurses@hitchcock.org
Rachel Wierzbicki, 6036505021
About this study
Official title: Genetically-informed Therapy for ER+ Breast Cancer in a Post-CDK4/6 Inhibitor Setting: a Phase II Umbrella Study (GERTRUDE)
The purpose of this study is to learn if certain drug combinations are effective treatments for patients with advanced ER+/HER2- who have previously been treated with palbociclib, ribociclib, or abemaciclib.
- Conditions
- Advanced Breast Cancer
- Being tested
- Fulvestrant, Neratinib, Alpelisib, Everolimus, Abemaciclib
- Keywords
- locally recurrent, metastatic, ER+, ER+/HER2-
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
Fulvestrant will be administered intramuscularly into the buttocks in combination with one of the other interventions as outlined above.
NeratinibDrug
Neratinib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above.
AlpelisibDrug
Alpelisib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above.
EverolimusDrug
Everolimus will be administered orally in tablet form once daily in combination with fulvestrant administration as outlined above.
AbemaciclibDrug
Abemaciclib will be administered orally in tablet form twice daily in combination with fulvestrant administration as outlined above.
| Study group | Role | What they receive |
|---|---|---|
| Arm A- neratinib and fulvestrant | Experimental | 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. Receives: Drug: Fulvestrant; Drug: Neratinib |
| Arm B- alpelisib and fulvestrant | Experimental | 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. Receives: Drug: Fulvestrant; Drug: Alpelisib |
| Arm C- everolimus and fulvestrant | Experimental | 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. Receives: Drug: Fulvestrant; Drug: Everolimus |
| Arm D- abemaciclib and fulvestrant | Experimental | 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. Receives: Drug: Fulvestrant; Drug: Abemaciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor.
Clinical benefit rate will be measured as the proportion of participants who experience stable disease (SD) at 24 weeks, complete response, and partial response per RECIST 1.1.
Measured: 6 - 12 months
Secondary outcomes (3)
Incidence rate of adverse events within each treatment arm.
Number of participants with treatment-related adverse events as assessed by CTCAE within each treatment arm.
Measured: 12 months
Progression-free survival within each treatment arm.
Progression-free survival will be measured by the time between the initiation of study treatment to the time of progression per RECIST 1.1.
Measured: 12 months
Rate of objective response within each treatment arm.
The proportion of participants within each arm who experience objective response defined as complete or partial response per RECIST 1.1 while on study treatment will be measured.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2023
- Study start23 Sep 2024
- Primary completionOct 2030 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This study has a non-randomized umbrella design. Participants will be assigned to a treatment arm based on tumor/plasma genetic profiling and treatment history using the primary treatment phase algorithm.
- Masking
- None (open label)
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mary D Chamberlin, Dartmouth-Hitchcock Medical Center
- Investigators
- Mary Chamberlin, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05933395
- Sponsor's protocol ID
- STUDY02001800
- Other IDs
- NCI-2024-09317
- Acronym
- GERTRUDE
- Status last verified
- Jan 2026
- First submitted
- 25 May 2023
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetically-informed Therapy for ER+ Breast Cancer in a Post-CDK4/6 Inhibitor Setting: a Phase II Umbrella Study (GERTRUDE)
- ClinicalTrials.gov ID
- NCT05933395
- Acronym / sponsor ID
- GERTRUDE / STUDY02001800
- Conditions
- Advanced Breast Cancer
- Keywords
- locally recurrent, metastatic, ER+, ER+/HER2-
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- 23 Sep 2024 (actual)
- Primary completion
- Oct 2030 (estimated)
- Study completion
- Oct 2031 (estimated)
- First posted
- 6 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn if certain drug combinations are effective treatments for patients with advanced ER+/HER2- who have previously been treated with palbociclib, ribociclib, or abemaciclib.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This study has a non-randomized umbrella design. Participants will be assigned to a treatment arm based on tumor/plasma genetic profiling and treatment history using the primary treatment phase algorithm.
| Arm | Type | Receives |
|---|---|---|
| Arm A- neratinib and fulvestrant | Experimental | Drug: Fulvestrant, Drug: NeratinibParticipants 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. |
| Arm B- alpelisib and fulvestrant | Experimental | Drug: Fulvestrant, Drug: AlpelisibIf 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. |
| Arm C- everolimus and fulvestrant | Experimental | Drug: Fulvestrant, Drug: EverolimusIf 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. |
| Arm D- abemaciclib and fulvestrant | Experimental | Drug: Fulvestrant, Drug: AbemaciclibIf 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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 be post-menopausal per NCCN guidelines.
- Patient must have been treated with a CDK4/6i (either palbobclib, ribociclib, or abemaciclib) alone or in combination with an endocrine agent in the advanced disease setting.
- Histologic documentation of ER+ breast cancer by core needle biopsy, fine needle aspiration, incisional biopsy, or surgical biopsy of ≥1 site(s) of metastatic or locally recurrent disease performed as standard of care.
- ER+ status defined as ER staining by immunohistochemistry in ≥1% of malignant cell nuclei.
Key exclusion criteria (4 listed)
- Treatment with abemaciclib in the most recent or current line of therapy.
- During the study Treatment Phases, no concurrent anti-cancer therapies are allowed with the following exception: anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
- Any investigational cancer therapy in the last 3 weeks.
- Known untreated CNS disease, unless clinically stable for ≥ 3 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FulvestrantFulvestrant will be administered intramuscularly into the buttocks in combination with one of the other interventions as outlined above. | Drug | Arm A- neratinib and fulvestrant, Arm B- alpelisib and fulvestrant, Arm C- everolimus and fulvestrant, Arm D- abemaciclib and fulvestrant |
| NeratinibNeratinib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above. | Drug | Arm A- neratinib and fulvestrant |
| AlpelisibAlpelisib will be administered orally in tablet form once daily with food in combination with fulvestrant administration as outlined above. | Drug | Arm B- alpelisib and fulvestrant |
| EverolimusEverolimus will be administered orally in tablet form once daily in combination with fulvestrant administration as outlined above. | Drug | Arm C- everolimus and fulvestrant |
| AbemaciclibAbemaciclib will be administered orally in tablet form twice daily in combination with fulvestrant administration as outlined above. | Drug | Arm D- abemaciclib and fulvestrant |
Primary outcome
Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor.
Time frame: 6 - 12 months
Clinical benefit rate will be measured as the proportion of participants who experience stable disease (SD) at 24 weeks, complete response, and partial response per RECIST 1.1.
3 secondary outcomes
Incidence rate of adverse events within each treatment arm.
Time frame: 12 months
Progression-free survival within each treatment arm.
Time frame: 12 months
Rate of objective response within each treatment arm.
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mary Chamberlin, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fulvestrant, Neratinib and Alpelisib in people with Advanced Breast Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Research Nurse (603-650-5021, hem-onc.research.nurses@hitchcock.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of clinical benefit within each arm in patients previously treated with a CDK4/6 inhibitor. (time frame: 6 - 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.