Anatomic Stage IV Breast Cancer AJCC v8Phase 1NCT04120246
Alpha-TEA and Trastuzumab for the Treatment of Refractory HER2+ Metastatic Breast Cancer
A Phase 1 study testing Alpha-tocopheryloxyacetic Acid and Trastuzumab in people with Anatomic Stage IV Breast Cancer AJCC v8 and HER2 Positive Breast Carcinoma, run by Veana Therapeutics at 2 sites in United States.
Trial summary
This phase I trial studies the side effects and best dose of alpha-TEA when given together with trastuzumab and to see how well they work for the treatment of HER2+ breast cancer that does not respond to treatment (refractory) and has spread to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, HER2 Positive Breast Carcinoma, Metastatic Breast Carcinoma
- What is being tested?
- Alpha-tocopheryloxyacetic Acid and Trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Apr 2020to 1 Feb 2030
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with HER2/neu overexpressing metastatic breast, not considered curable by conventional therapies
- HER2 positivity will be defined per the 2018 ASCO/CAP guidelines (JCO 2018)
- Has measurable extra-skeletal disease per RECIST 1.1
- Patients who have received recommended first therapy with a Taxane, with trastuzumab and/or pertuzumab and second line therapy with Kadcyla (ado-trastuzumab emtansine) or ENHERTU (fam-trastuzumab deruxtecan-nxki) or are unable to tolerate these therapies are eligible to participate.
- Patients must continue trastuzumab or biosimilars of trastuzumab with or without pertuzumab dosing per standard of care through the entire study period.
- Prior Lapatinib in the metastatic setting is allowed, but not required.
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- Patients with ER and / or PR positive metastatic breast cancer are eligible and may continue anti-estrogen therapy for the duration of the study.
- Patients must be at least 14 days post cytotoxic chemotherapy prior to enrollment.
- Patients on bisphosphonates and/or endocrine therapy are eligible and can continue on this therapy concurrently.
- Women who are having sex that can lead to pregnancy must have a negative pregnancy test within 28 days prior to enrollment and must avoid becoming pregnant while on α-TEA and for 4 weeks after the last dose of α-TEA and 7 months after Herceptin/biosimilars (see section 7.3). Men must avoid fathering a child while on α-TEA and for 4 weeks after the last dose of α-TEA.
- Patients must have ECOG Performance Status Score of ≤ 2 (Appendix A).
- Patients must have recovered from major infections and/or major surgical procedures, and in the opinion of the investigator, not have significant active concurrent medical illnesses precluding study treatment.
- Laboratory values must be as follows and performed within 28 days prior to first treatment
- WBC ≥ 2000/mm3
- Hgb ≥ 8 mg/dl
- Estimated creatinine clearance (Clcr) by the Cockcroft-Gault (G-C) equation ≥ 60 mL/min
- Total bilirubin ≤ 1.5 x upper limit of normal
- AST <2.5 X upper limit of laboratory normal
- ALT<2.5 X upper limit of laboratory normal
- Alkaline phosphatase <2.5 X upper limit of laboratory normal
- INR <1.5
- PT <16 seconds
- PTT < 38 seconds
- TSH ≤ 5
- Free T4 ≥ .9
- Ability to swallow capsules.
- Patients must be at least 18 years of age.
- Patients must have adequate cardiac function as demonstrated by normal left ventricular ejection fraction (LVEF) ≥ the lower limit of normal for the facility (or ≥50%) on MUGA scan or echocardiogram (ECHO) within 3 months of enrollment.
- Must be off Vitamin E supplements (multivitamin acceptable) for at least two weeks prior to first dose of study drug
Who cannot join
- 1. Patients with any of the following cardiac conditions:
- Restrictive cardiomyopathy
- Unstable angina within 6 months prior to enrollment
- New York Heart Association functional class III-IV heart failure
- Symptomatic pericardial effusion
- Right atrial enlargement on ECHO would not be allowed. 2. History of or active atrial fibrillation or supraventricular tachycardia 3. History of documented cardiac arrhythmia 4. Active cardiac ischemia. Patients with a history of ischemia ameliorated with stent placement or coronary artery bypass grafting and who have no evidence of ischemia by exercise or physiological stress testing are eligible.
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- 5. Patients with any clinically significant autoimmune disease requiring active treatment.
- 6. Patients receiving any concurrent systemic immunosuppressants within 14 days of enrollment. Patients who require brief courses of steroids to manage allergic reaction to intravenous contrast used in radiographic studies are eligible.
- 7. Patients receiving strong inhibitors or inducers of CYP3A4/5. (See Appendix B - Patients must be off at least 2 weeks prior to first dose of IP) 8. Patients who are pregnant or breast-feeding. 9. Patients who are simultaneously enrolled in other treatment studies for active treatment.
- 10. Active brain metastatic disease. Patients with brain metastases who have been treated with surgery, gamma-knife radiosurgery or radiation and no radiographic progression for at least 4 weeks and off steroids for 14 days are eligible.
- 11. No leptomeningeal disease. 12. Any medical or psychiatric condition that in the opinion of the PI would preclude compliance with study procedures.
- 13. Malabsorption state such as ulcerative colitis, previous surgical resection of > 20% of intestine or stomach.
- 14. Surgery or severe trauma within 4 weeks of study entry (minimally invasive procedures acceptable).
- 15. QTc greater than 450 msec at (calculated using Bazett's formula), sick-sinus syndrome or other active cardiac disease.
- 16. Patient with abnormal thyroid function or who are euthyroid but on medication for thyroid disorders must be excluded.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Providence Cancer Institute - Franz Clinic
Portland, Oregon, 97213
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: A Phase I Dose Escalation Trial of Alpha-Tocopheryloxyacetic Acid (α-TEA) in Patients With Treatment Refractory HER2+ Metastatic Breast Cancer
This phase I trial studies the side effects and best dose of alpha-TEA when given together with trastuzumab and to see how well they work for the treatment of HER2+ breast cancer that does not respond to treatment (refractory) and has spread to other places in the body (metastatic). Anti-cancer treatment, such as alpha-TEA, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Alpha-TEA may also alter cancer growth by stimulating the body's immune response against the tumor. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Giving alpha-TEA and trastuzumab may work better for the treatment of HER2+ refractory and metastatic breast cancer compared to usual treatment.
Read the detailed description
OUTLINE:
This is a dose-escalation study of alpha-TEA.
Patients receive one of 4 doses of alpha-TEA orally (PO) on days 1-14 of each cycle. Patients also receive trastuzumab on day 1 of cycle 1 and then every 3 weeks per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 4 years.
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, HER2 Positive Breast Carcinoma, Metastatic Breast Carcinoma, Refractory Breast Carcinoma
- Being tested
- Alpha-tocopheryloxyacetic Acid, Trastuzumab
- Keywords
- Breast, HER2+, metastatic, refractory, immunotherapy
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-tocopheryloxyacetic AcidDrug
Also called 12-trimethyltridecyl) chroman-6-yloxy) Acetic Acid, a-TEA, alpha-TEA, 261929-52-6
Given PO
TrastuzumabBiological
Also called 180288-69-1, 688097, ABP 980, Anti-c-ERB-2
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (alpha-TEA, trastuzumab) | Experimental | Patients receive one of 4 doses of alpha-TEA PO on days 1-14 of each cycle. Patients also receive trastuzumab on day 1 of cycle 1 and then every 3 weeks per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Alpha-tocopheryloxyacetic Acid; Biological: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events of 4 escalating doses of alpha-tocopheryloxyacetic acid (TEA) therapy when combined with trastuzumab
Toxicity grading will be evaluated per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Measured: Up to 4 years
Clinical response rate of alpha-TEA when combined with trastuzumab
Clinical response will be performed by computed tomography (CT) scan of the chest, abdomen, and pelvis performed prior to enrollment and then after every 3 cycles per standard of care. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and immune related (ir)RECIST criteria will be used to determine response. Both progression free survival (PFS) and overall survival (OS) will be measured.
Measured: Up to 4 years
Secondary outcomes (3)
Change in level of activated effector memory CD4+ and CD8+ T-cells at 4 escalating doses of alpha-TEA and concurrent trastuzumab
The level of memory CD4+ and CD8+ T cells will be evaluated by flow cytometry. Memory CD4+ T cells will be defined as CD3+CD4+CD38+HLA-DR+CCR7-CD45RA- and memory CD8+ T cells will be defined as CD3+CD8+CD38+ HLA-DR+CCR7-CD45RA-.
Measured: At baseline, at cycle 4 Day 1, and then Day 1 of every 4th cycle while on study (each cycle is 28 days), assessed up to 4 years
Change in the number of HER2 specific T cells at each dose level
Will determine if concurrent alpha-TEA and trastuzumab increase the number of HER2 specific T cells at each dose level. Endogenous immunity to HER2 will be evaluated using interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assay. A statistically significant increase of HER2 specific immunity after concurrent alpha-TEA and trastuzumab treatment when compared to baseline will constitute augmentation of HER2 specific immunity.
Measured: Baseline up to 4 years
Modulation of circulating natural killer (NK) cells with concurrent alpha-TEA and trastuzumab therapy
Flow cytometry will be used to assess the number of NK cells as defined by CD3-CD16+CD56+ cells from whole blood. Flow will be used to analyze the function of NK cells, specifically through degranulation markers (CD107a+) and through IFN-gamma production. The level of NK cell CD107+ uptake and IFN-gamma production in response to major histocompatibility complex (MHC) class 1 negative cell will be evaluated.
Measured: At baseline, at cycle 4 Day 1, and then Day 1 of every 4th cycle while on study (each cycle is 28 days), assessed up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start8 Apr 2020
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Feb 2030 (estimated)
Why it stopped: Study placed on hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Veana Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Washington
- Responsible party
- Sponsor
- Investigators
- William Gwin, MD, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04120246
- Sponsor's protocol ID
- RG1004302
- Other IDs
- NCI-2019-06457, 8790
- Status last verified
- Jul 2024
- First submitted
- 7 Oct 2019
- Last updated
- 10 Jul 2024
- 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 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Trial of Alpha-Tocopheryloxyacetic Acid (α-TEA) in Patients With Treatment Refractory HER2+ Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT04120246
- Acronym / sponsor ID
- RG1004302
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, HER2 Positive Breast Carcinoma, Metastatic Breast Carcinoma, Refractory Breast Carcinoma
- Keywords
- Breast, HER2+, metastatic, refractory, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Study placed on hold.
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Veana TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- University of Washington
- Study start
- 8 Apr 2020 (actual)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Feb 2030 (estimated)
- First posted
- 9 Oct 2019 (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.
This phase I trial studies the side effects and best dose of alpha-TEA when given together with trastuzumab and to see how well they work for the treatment of HER2+ breast cancer that does not respond to treatment (refractory) and has spread to other places in the body (metastatic). Anti-cancer treatment, such as alpha-TEA, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Alpha-TEA may also alter cancer growth by stimulating the body's immune response against the tumor. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Giving alpha-TEA and trastuzumab may work better for the treatment of HER2+ refractory and metastatic breast cancer compared to usual treatment.
Detailed description
OUTLINE:
This is a dose-escalation study of alpha-TEA.
Patients receive one of 4 doses of alpha-TEA orally (PO) on days 1-14 of each cycle. Patients also receive trastuzumab on day 1 of cycle 1 and then every 3 weeks per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (alpha-TEA, trastuzumab) | Experimental | Drug: Alpha-tocopheryloxyacetic Acid, Biological: TrastuzumabPatients receive one of 4 doses of alpha-TEA PO on days 1-14 of each cycle. Patients also receive trastuzumab on day 1 of cycle 1 and then every 3 weeks per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Patients with HER2/neu overexpressing metastatic breast, not considered curable by conventional therapies
- Patients who have received recommended first therapy with a Taxane, with trastuzumab and/or pertuzumab and second line therapy with Kadcyla (ado-trastuzumab emtansine) or ENHERTU (fam-trastuzumab deruxtecan-nxki) or are unable to tolerate these therapies are eligible to participate.
- Patients must continue trastuzumab or biosimilars of trastuzumab with or without pertuzumab dosing per standard of care through the entire study period.
- Prior Lapatinib in the metastatic setting is allowed, but not required.
- Patients with ER and / or PR positive metastatic breast cancer are eligible and may continue anti-estrogen therapy for the duration of the study.
Key exclusion criteria (15 listed)
- 1. Patients with any of the following cardiac conditions:
- 5. Patients with any clinically significant autoimmune disease requiring active treatment.
- 6. Patients receiving any concurrent systemic immunosuppressants within 14 days of enrollment. Patients who require brief courses of steroids to manage allergic reaction to intravenous contrast used in radiographic studies are eligible.
- 7. Patients receiving strong inhibitors or inducers of CYP3A4/5. (See Appendix B - Patients must be off at least 2 weeks prior to first dose of IP) 8. Patients who are pregnant or breast-feeding. 9. Patients who are simultaneously enrolled in other treatment studies for active treatment.
- 10. Active brain metastatic disease. Patients with brain metastases who have been treated with surgery, gamma-knife radiosurgery or radiation and no radiographic progression for at least 4 weeks and off steroids for 14 days are eligible.
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 |
|---|---|---|
| Alpha-tocopheryloxyacetic AcidAlso: 12-trimethyltridecyl) chroman-6-yloxy) Acetic Acid, a-TEA, alpha-TEA, 261929-52-6Given PO | Drug | Treatment (alpha-TEA, trastuzumab) |
| TrastuzumabAlso: 180288-69-1, 688097, ABP 980, Anti-c-ERB-2Given IV | Biological | Treatment (alpha-TEA, trastuzumab) |
Primary outcome
Incidence of adverse events of 4 escalating doses of alpha-tocopheryloxyacetic acid (TEA) therapy when combined with trastuzumab
Time frame: Up to 4 years
Toxicity grading will be evaluated per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Clinical response rate of alpha-TEA when combined with trastuzumab
Time frame: Up to 4 years
Clinical response will be performed by computed tomography (CT) scan of the chest, abdomen, and pelvis performed prior to enrollment and then after every 3 cycles per standard of care. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and immune related (ir)RECIST criteria will be used to determine response. Both progression free survival (PFS) and overall survival (OS) will be measured.
3 secondary outcomes
Change in level of activated effector memory CD4+ and CD8+ T-cells at 4 escalating doses of alpha-TEA and concurrent trastuzumab
Time frame: At baseline, at cycle 4 Day 1, and then Day 1 of every 4th cycle while on study (each cycle is 28 days), assessed up to 4 years
Change in the number of HER2 specific T cells at each dose level
Time frame: Baseline up to 4 years
Modulation of circulating natural killer (NK) cells with concurrent alpha-TEA and trastuzumab therapy
Time frame: At baseline, at cycle 4 Day 1, and then Day 1 of every 4th cycle while on study (each cycle is 28 days), assessed up to 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- 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. This study is not recruiting at the moment.
William Gwin, MD principal investigator
Fred Hutch/University of Washington Cancer Consortium
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Alpha-tocopheryloxyacetic Acid and Trastuzumab in people with Anatomic Stage IV Breast Cancer AJCC v8 and HER2 Positive Breast Carcinoma, run by Veana Therapeutics at 2 sites 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 29 inclusion and 15 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: paused, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events of 4 escalating doses of alpha-tocopheryloxyacetic acid (TEA) therapy when combined with trastuzumab (time frame: Up to 4 years). The study lists 2 primary outcomes in all. 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 10 Jul 2024.