HER2-positive Breast CancerNCT05750693
PIK3CA in HER2+ BC and pCR Trial
A study testing PIK3CA analysis in people with HER2-positive Breast Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The goal of the study is to evaluate the impact of somatic PI3KCA mutations on pCR in HER2-positive early breast cancer in real life. The main question it aims to answer iS. Is there a correlation between PIK3CA mutations and response to neoadjuvant chemotherapy in HER2 early breast cancer? Participants who received… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- HER2-positive Breast Cancer
- What is being tested?
- PIK3CA analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteItaly
- Study dates
- 2 May 2022to 1 Sep 2023
- Phase
- Interventional
- 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
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Age older than 18 years.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy.
- Tumor lesion in the breast with a palpable size of ≥ 2 cm and/or ≥ 1.5 cm by ultrasound or magnetic resonance imaging (MRI). In case of inflammatory carcinoma the extent of inflammation can be used as measurable lesion.
- American Joint Commission on Cancer stage II or III invasive breast cancer.
- Known estrogen (ER)- and progesterone (PgR)-receptor negative or positive tumors.
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- Known HER-2/neu positive tumors, defined as HercepTest IHC 3+ or SISH+.
- Patients suitable for neoadjuvant chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2 or Karnowsky performance status index at least 80%.
- Normal cardiac function must be confirmed by ECG and cardiac ultrasound (LVEF or shortening fraction) within 1 month prior to registration.
- Laboratory requirements:
- Hematology: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, Hemoglobin ≥ 10 g/dL.
- Hepatic function: Total bilirubin < 1 x UNL, ASAT (SGOT) and ALAT (SGPT)≤ 2.5 x UNL, Alkaline phosphatase ≤ 5 UNL. Patients with ASAT and / or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study.
- Renal function: Creatinine ≤ 2 mg/dL, < 1,25 UNL (or the calculated creatinine clearance ≥ 60 mL/min).
- Paraffin tumor tissue block made available.
- Availability to provide the set up of the histological preparations for molecular analysis.
- Negative pregnancy test (urine or serum).
- Patients must be available and compliant for treatment and follow-up.
Who cannot join
- Patients candidate for adjuvant chemotherapy.
- Evidence of distant metastasis.
- Prior chemotherapy for any malignancy.
- Prior radiation therapy for breast cancer.
- Pregnant or lactating patients.
- Inadequate general condition.
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- Previous malignant disease.
- Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ECG, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease.
- History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, RM, 00168
About this study
Official title: Impact of Somatic PIK3CA Mutations on Pathological Complete Response (pCR) in HER2-positive Early Breast Cancer.
The goal of the study is to evaluate the impact of somatic PI3KCA mutations on pCR in HER2-positive early breast cancer in real life. The main question it aims to answer iS.
- Is there a correlation between PIK3CA mutations and response to neoadjuvant chemotherapy in HER2 early breast cancer? Participants who received neoadjuvant chemotherapy in addition to anti-Her2 target therapy will undergo PIK3CA analysis in order to answer to this question.
Read the detailed description
Women with breast cancer (BC) overexpressing HER2 have more aggressive tumors and, without administration of anti-HER2agents, a shorter disease-free survival (DFS) and overall survival (OS) compared to patients with HER2-negative subtypes. Since the introduction of trastuzumab, the course of HER2-positive BC has notably improved in both metastatic and early settings. Indeed, anti-HER2 treatment has influenced the response to neoadjuvant (NAD). Women with breast cancer (BC) overexpressing HER2 have more aggressive tumors and, without administration of anti-HER2agents, a shorter disease-free survival (DFS) and overall survival (OS) compared to patients with HER2-negative subtypes. Since the introduction of trastuzumab, the course of HER2-positive BC has notably improved in both metastatic and early settings. Indeed, anti-HER2 treatment has influenced the response to neoadjuvant (NAD) therapy in HER2-positive BC by increasing the pCR rate. However, primary and acquired resistance to trastuzumab-containing regimens remains one of the major issues in clinical practice. Selecting patients that will benefit from anti-HER2 treatment is therefore essential. Overexpression of HER2 is identified in ∼20% of early-stage invasive BC and induces the downstream activation of the PI3K/AKT/mTOR pathway that plays a crucial role in developing resistance to trastuzumab: PIK3CA mutation and PTEN protein loss cause an hyperactivation of the pathway, whereas PIK3CA wild-type and retained or increased PTEN expression lead to a lower activation. PIK3CA mutations are predominantly found in hotspots located in the helical and kinase domains (exons 9 and 20), resulting in activation of the kinase. Another potential mechanism of resistance to trastuzumab is the estrogen receptor (ER) in those tumors that express both ER and HER2. To date, resistance biomarkers are lacking: despite the fact that data on PIK3CA mutations demonstrate significantly lower pCR rates, this has not led to an inclusion of the marker into routine diagnostics. PIK3CA can be investigated together with HER2 in pre-NAD tissue samples, in order to evaluate the correlation with response to NAD chemotherapy. That is an optimal setting to understand if PI3K could be considered a biomarker for HER2 therapy-resistant tumors and to select patients with poorer prognosis.
This study investigates the association of pCR with PIK3CA mutations and ER status and their prognostic value in HER2-positive BC treated with anti-HER2 therapy in addition to NAD chemotherapy.
Response to NAD therapy will be determined as pCR, defined as no invasive residuals in breast tissue and lymph nodes (ypT0/is, ypN0). Disease-free survival (DFS) will be defined as time in months from randomization to (local or distant) disease recurrence, secondary malignancy or death due to any cause. Overall survival (OS) was defined as time in months from randomization to death due to any cause.
- Conditions
- HER2-positive Breast Cancer
- Being tested
- PIK3CA analysis
- Keywords
- PIK3CA, Neoadjuvant chemotherapy, pathologic complete response, Her-2
- Medical subject headings
- Hereditary Sensory and Autonomic Neuropathies, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PIK3CA analysisGenetic
PIK3CA will be investigated together with HER2 in pre-NAD tissue samples, in order to evaluate the correlation with response to NAD chemotherapy, with a 16-gene MYRIAPOD kit. This evaluation will be performed on all 58 patients in the study for group (responders and not responders).
Moreover 10 patient samples (5 responders and 5 non-responders) will be subjected to gene expression profile analysis. Specifically, a transcriptomic analysis will be performed on total RNA from one inch of cells (10-50 cells isolated by LCM from FFPE biopsy, RNA seq) which will allow to have the transcriptional profile for each patient of protein-coding transcripts (coding RNAs) and long non-coding RNAs.
In addition, an NGS analysis by TSO500 will be performed in parallel, on the slide following the previous one, to have the genome sequence (523 genes) on the same 10-50 cells isolated by LCM from FFPE biopsy for the identification of any mutations.
| Study group | Role | What they receive |
|---|---|---|
| Patients who received neoadjuvant chemotherapy | Experimental | Breast cancer samples of paraffin embedded tissue, obtained from the waste material of the diagnostic core-biopsy, stored at the Pathological Anatomy Service, will be used in order to analyze PIK3CA mutations status. Receives: Genetic: PIK3CA analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathologic complete response
To investigate the association of pCR and PIK3CA mutations in patients with locally advanced HER-2 positive Breast Cancer.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2023
- Study start2 May 2022
- Primary completion1 Sep 2023 (estimated)
- Study completion1 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05750693
- Sponsor's protocol ID
- 4469
- Status last verified
- Feb 2023
- First submitted
- 20 Feb 2023
- Last updated
- 2 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Somatic PIK3CA Mutations on Pathological Complete Response (pCR) in HER2-positive Early Breast Cancer.
- ClinicalTrials.gov ID
- NCT05750693
- Acronym / sponsor ID
- 4469
- Conditions
- HER2-positive Breast Cancer
- Keywords
- PIK3CA, Neoadjuvant chemotherapy, pathologic complete response, Her-2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 2 May 2022 (actual)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 Sep 2023 (estimated)
- First posted
- 2 Mar 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 goal of the study is to evaluate the impact of somatic PI3KCA mutations on pCR in HER2-positive early breast cancer in real life. The main question it aims to answer iS.
- Is there a correlation between PIK3CA mutations and response to neoadjuvant chemotherapy in HER2 early breast cancer? Participants who received neoadjuvant chemotherapy in addition to anti-Her2 target therapy will undergo PIK3CA analysis in order to answer to this question.
Detailed description
Women with breast cancer (BC) overexpressing HER2 have more aggressive tumors and, without administration of anti-HER2agents, a shorter disease-free survival (DFS) and overall survival (OS) compared to patients with HER2-negative subtypes. Since the introduction of trastuzumab, the course of HER2-positive BC has notably improved in both metastatic and early settings. Indeed, anti-HER2 treatment has influenced the response to neoadjuvant (NAD). Women with breast cancer (BC) overexpressing HER2 have more aggressive tumors and, without administration of anti-HER2agents, a shorter disease-free survival (DFS) and overall survival (OS) compared to patients with HER2-negative subtypes. Since the introduction of trastuzumab, the course of HER2-positive BC has notably improved in both metastatic and early settings. Indeed, anti-HER2 treatment has influenced the response to neoadjuvant (NAD) therapy in HER2-positive BC by increasing the pCR rate. However, primary and acquired resistance to trastuzumab-containing regimens remains one of the major issues in clinical practice. Selecting patients that will benefit from anti-HER2 treatment is therefore essential. Overexpression of HER2 is identified in ∼20% of early-stage invasive BC and induces the downstream activation of the PI3K/AKT/mTOR pathway that plays a crucial role in developing resistance to trastuzumab: PIK3CA mutation and PTEN protein loss cause an hyperactivation of the pathway, whereas PIK3CA wild-type and retained or increased PTEN expression lead to a lower activation. PIK3CA mutations are predominantly found in hotspots located in the helical and kinase domains (exons 9 and 20), resulting in activation of the kinase. Another potential mechanism of resistance to trastuzumab is the estrogen receptor (ER) in those tumors that express both ER and HER2. To date, resistance biomarkers are lacking: despite the fact that data on PIK3CA mutations demonstrate significantly lower pCR rates, this has not led to an inclusion of the marker into routine diagnostics. PIK3CA can be investigated together with HER2 in pre-NAD tissue samples, in order to evaluate the correlation with response to NAD chemotherapy. That is an optimal setting to understand if PI3K could be considered a biomarker for HER2 therapy-resistant tumors and to select patients with poorer prognosis.
This study investigates the association of pCR with PIK3CA mutations and ER status and their prognostic value in HER2-positive BC treated with anti-HER2 therapy in addition to NAD chemotherapy.
Response to NAD therapy will be determined as pCR, defined as no invasive residuals in breast tissue and lymph nodes (ypT0/is, ypN0). Disease-free survival (DFS) will be defined as time in months from randomization to (local or distant) disease recurrence, secondary malignancy or death due to any cause. Overall survival (OS) was defined as time in months from randomization to death due to any cause.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients who received neoadjuvant chemotherapy | Experimental | Genetic: PIK3CA analysisBreast cancer samples of paraffin embedded tissue, obtained from the waste material of the diagnostic core-biopsy, stored at the Pathological Anatomy Service, will be used in order to analyze PIK3CA mutations status. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Written informed consent.
- Age older than 18 years.
- Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy.
- Tumor lesion in the breast with a palpable size of ≥ 2 cm and/or ≥ 1.5 cm by ultrasound or magnetic resonance imaging (MRI). In case of inflammatory carcinoma the extent of inflammation can be used as measurable lesion.
- American Joint Commission on Cancer stage II or III invasive breast cancer.
Key exclusion criteria (9 listed)
- Patients candidate for adjuvant chemotherapy.
- Evidence of distant metastasis.
- Prior chemotherapy for any malignancy.
- Prior radiation therapy for breast cancer.
- Pregnant or lactating patients.
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 |
|---|---|---|
| PIK3CA analysisPIK3CA will be investigated together with HER2 in pre-NAD tissue samples, in order to evaluate the correlation with response to NAD chemotherapy, with a 16-gene MYRIAPOD kit. This evaluation will be performed on all 58 patients in the study for group (responders and not responders). Moreover 10 patient samples (5 responders and 5 non-responders) will be subjected to gene expression profile analysis. Specifically, a transcriptomic analysis will be performed on total RNA from one inch of cells (10-50 cells isolated by LCM from FFPE biopsy, RNA seq) which will allow to have the transcriptional profile for each patient of protein-coding transcripts (coding RNAs) and long non-coding RNAs. In addition, an NGS analysis by TSO500 will be performed in parallel, on the slide following the previous one, to have the genome sequence (523 genes) on the same 10-50 cells isolated by LCM from FFPE biopsy for the identification of any mutations. | Genetic | Patients who received neoadjuvant chemotherapy |
Primary outcome
pathologic complete response
Time frame: 7 months
To investigate the association of pCR and PIK3CA mutations in patients with locally advanced HER-2 positive Breast Cancer.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PIK3CA analysis in people with HER2-positive Breast Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 18 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 2 Mar 2023. 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 Italy. 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.
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?
pathologic complete response (time frame: 7 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 2 Mar 2023.