Breast Cancer, PI3K, AlpelisibPhase 2SAFIR-PI3KNCT03386162
SAFIR-PI3K A Phase II Randomized Maintenance Trial Comparing Alpelisib and Fulvestrant Versus Chemotherapy in PIK3CA Mutated Advanced Breast Cancer
A Phase 2 study testing Alpelisib and Chemotherapy in people with Breast Cancer, PI3K, Alpelisib, run by UNICANCER at 14 sites in France.
Trial summary
SAFIR PI3K is an open-label multicenter phase II randomized trial, comparing alpelisib plus fulvestrant to maintenance chemotherapy in patient PIK3CA mutated with HR+/Her2- metastatic breast cancer who do not present progressive disease after 6-8 cycles of 1st or second line chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, PI3K, Alpelisib
- What is being tested?
- Alpelisib and Chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 14 sitesFrance
- Study dates
- 15 Mar 2018to 18 Nov 2022
- Phase
- Phase 2
- 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
- Women (or men) with histologically confirmed metastatic breast cancer.
- Hormone receptor positive (HR+) and no Her2 over-expression, according to local assessment.
- Presence of PIK3CA mutation on exon 9 or 20, determined on metastatic tissue specimen (frozen or FFPE) or plasma (ctDNA). Eligible plasma should have been collected at time of metastatic disease progression and before to initiating chemotherapy.
- Patient's disease is resistant to endocrine therapy (defined either as a relapse or progression occurred during endocrine therapy, whatever the line, or less than 12 months after the end of endocrine therapy in adjuvant context).
- Patients who received 6 to 8 cycles of a first line chemotherapy, or patients who received 6 to 8 cycles of a first line stopped for progression followed by 6 to 8 cycles of a 2nd line chemotherapy, and who are presenting a stable or a responding disease at the time of randomization (4 full cycles of chemotherapy are accepted if stopped for toxicity reasons)
- Age ≥18 years
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- WHO Performance Status 0/1
- Presence of measurable or evaluable disease according to RECIST criteria v1.1
- Patients will have had a wash-out period of at least 14 days for weekly (except monoclonal antibodies) or daily chemotherapies or 28 days for other chemotherapies from last chemotherapy administration prior to randomization and should have recovered from all residual toxicities (grade ≤1), excluding alopecia.
- Patient has adequate bone marrow and organ function as defined by the following laboratory values:
- Absolute Neutrophil Count (ANC) ≥1.5 x 10⁹/L
- Platelets ≥100 x 10⁹/L
- Hemoglobin ≥9.0 g/dL
- International normalized ratio (INR) ≤1.5
- Potassium, magnesium and calcium (corrected for albumin), within normal limits for the institution, or ≤Grade 1 severity according to NCI-CTCAE version 4.03 if judged clinically not significant by the investigator
- Serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance ≥50 mL/min (Measured or calculated by Cockcroft and Gault formula)
- Total serum bilirubin ≤ ULN (or ≤1.5 x ULN if liver metastases are present; or total bilirubin ≤3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome)
- Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤2.5 ULN (or <5.0 x ULN if liver metastases are present)
- Fasting plasma glucose (FPG) ≤140 mg/dL or ≤7.7 mmol/L* and Glycosylated Hemoglobin (HbA1c) ≤6.4% (both criteria have to be met).
- For patients with FPG ≥100 mg/dL or HbA1c ≥5.7% (i.e. threshold for pre-diabetes) at baseline, recommend lifestyle changes according to ADA guidelines, i.e. dietary advice (e.g. small frequent meals, low carbohydrate content, high fiber, balancing carbohydrate intake over the course of the day, three small meals and 2 small snacks rather than one large meal) and exercise. A consultation with a diabetologist is highly recommended
- Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analysis
- Patient with social insurance coverage.
Who cannot join
- Spinal cord compression or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable without steroids during the last 30 days).
- Patient has received more than 2 previous lines of chemotherapy for metastatic disease before randomization.
- Prior exposure to anthracyclines or mitoxantrone with cumulative exposure in excess of 360 mg/m² for doxorubicin, 720 mg/m² for epirubicin, or 72 mg/m² for mitoxantrone.
- In the Investigator's judgment, patient has a life expectancy <3 months .
- Disease progression occuring before randomization.
- Patient has received prior treatment with any PI3K or AKT inhibitor (mTOR inhibitors are allowed)
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- Patient has history of hypersensitivity to any drugs or metabolites of similar chemical classes as alpelisib, or history of hypersensitivity to active or inactive excipients of any other study treatment.
- Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
- Patient has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) or from whom ≥25% of the bone marrow was irradiated
- Patient has participated to another clinical study with an investigational product during the last 30 days.
- Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects
- Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study treatment, or has not fully recovered from side effects of such treatment
- Patients with an established diagnosis of diabetes mellitus type I or not controlled type II, or documented steroid induced diabetes mellitus
- Patient who necessitates to maintain the following drugs during study treatment :
- Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A4 including herbal medications (list of prohibited CYP3A4 inhibitors and inducers provided in Table 12)
- Drugs with a known risk to induce Torsades de Pointes (list of prohibited QT prolonging drugs provided in Table 12) Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the study treatment is initiated. Switching to a different medication prior to starting study treatment is allowed.
- Patient is currently receiving warfarin or other coumarin derived anti-coagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
- Patients who have other concurrent severe or uncontrolled medical conditions that would, in the Investigator's judgment, contraindicate patient participation in the individual patient program (eg. active or uncontrolled severe infection, chronic active hepatitis, immuno-compromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
- Patient has currently documented pneumonitis
- Patient has a known history of HIV infection (testing not mandatory)
- Patient has any of the following cardiac abnormalities:
- symptomatic congestive heart failure
- history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy
- Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- myocardial infarction ≤6 months prior to enrolment
- unstable angina pectoris
- serious uncontrolled cardiac arrhythmia
- symptomatic pericarditis
- QTcF >480 msec on the baseline ECG (using the QTcF formula) currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment (list of prohibited QT prolonging drugs provided in Table 12)
- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of any study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- Patient had previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
- Pregnant or nursing (lactating) women.
- Patient who does not accept to comply with highly effective contraception methods during the study treatment and through the duration as defined below after the final dose of study treatment:
- Sexually active males should use a condom during intercourse while taking drug and for at least 4 weeks after the final dose of study treatment and should not father a child in this period.
- Women of child-bearing potential must use highly effective contraception during study treatment and for at least 4 weeks after the final dose of study treatment and until resumption of menses (if longer than 4 weeks).
- Patient has a history of non-compliance to medical regimen or inability to grant consent
- Individuals deprived of liberty or placed under the authority of a tutor
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
France14 sites
Institut de Cancérologie de l'Ouest/Paul Papin
Angers
Institut Sainte-Catherine
Avignon
Institut Bergonié
Bordeaux
Centre François Baclesse
Caen
Chd Vendee
La Roche-sur-Yon
CHU Dupuytren
Limoges
Centre Leon Berard
Lyon
Institut Paoli Calmettes
Marseille
CInstitut Regional du cancer-Centre Val D'Aurelle
Montpellier
Centre Eugène Marquis
Rennes
Centre Rene Huguenin
Saint-Cloud, 92211
Hôpitaux du Léman
Thonon-les-Bains, 74200
Institut Claudius Regaud
Toulouse
Institut Gustave Roussy
Villejuif
About this study
Official title: A Phase II Randomized Trial Comparing Alpelisib and Fulvestrant Versus Chemotherapy as Maintenance Therapy in Patients With PIK3CA Mutated Advanced Breast Cancer
SAFIR PI3K is an open-label multicenter phase II randomized trial, comparing alpelisib plus fulvestrant to maintenance chemotherapy in patient PIK3CA mutated with HR+/Her2- metastatic breast cancer who do not present progressive disease after 6-8 cycles of 1st or second line chemotherapy.
The primary objective is to determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to maintenance chemotherapy in patients PIK3CA mutated with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who do not present a progressive disease after 6-8 cycles of chemotherapy.
- Conditions
- Breast Cancer, PI3K, Alpelisib
- Being tested
- Alpelisib, Chemotherapy
- Keywords
- Breast cancer, PI3K, alpelisib
- Medical subject headings
- Breast Neoplasms, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlpelisibDrug
Also called fulvestrant
fulvestrant (500 mg intramuscular [as two 5 mL injections] every 28 days ± 3 days, with an additional injection on 15 after the first administration + Alpelisib (300 mg by mouth once daily, in a 21-day cycle). Premenopausal women will receive LH-RH analogs in addition every 28 days ± 3 days.
ChemotherapyDrug
maintenance chemotherapy, meaning the same chemotherapy regimen used during the first 6-8 cycles (investigator's choice) or no antineoplastic treatment in case of toxicity after 4 full cycles.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm (Arm A3) | Experimental | fulvestrant (500 mg intramuscular [as two 5 mL injections] every 28 days ± 3 days, with an additional injection on 15 after the first administration + Alpelisib (300 mg by mouth once daily, in a 21-day cycle). Premenopausal women will receive LH-RH analogs in addition every 28 days ± 3 days. Receives: Drug: Alpelisib |
| Control arm (Arm B3) | Active comparator | maintenance chemotherapy, meaning the same chemotherapy regimen used during the first 6-8 cycles (investigator's choice) or no antineoplastic treatment in case of toxicity after 4 full cycles. Receives: Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to maintenance chemotherapy in patients PIK3CA mutated with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who do not present a progressive disease after 6-8 cycles of chemotherapy.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2017
- Study start15 Mar 2018
- Primary completion18 Nov 2022
- Study completion18 Nov 2022
Why it stopped: Study was halted Prematurely for low recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer, PI3K, AlpelisibStudies of the same condition, open and under way.
- More trials run by UNICANCERThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In the randomized treatment phase, patients will be randomized 2:1 to receive: • Experimental arm (Arm A3): fulvestrant (500 mg intramuscular \[as two 5 mL injections\] every 28 days ± 3 days, with an additional injection on 15 after the first administration + Alpelisib (300 mg by mouth once daily, in a 21-day cycle). Premenopausal women will receive luteinizing hormone-releasing hormone (LH-RH) analogs in addition every 28 days ± 3 days. OR • Control arm (Arm B3): maintenance chemotherapy, meaning the same chemotherapy regimen used during the first 6-8 cycles (investigator's choice) or no antineoplastic treatment in case of toxicity after 4 full cycles. A total of approximately 90 patients will be enrolled
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03386162
- Sponsor's protocol ID
- UC-0105/1701
- Acronym
- SAFIR-PI3K
- Status last verified
- Nov 2022
- First submitted
- 21 Dec 2017
- Last updated
- 28 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized Trial Comparing Alpelisib and Fulvestrant Versus Chemotherapy as Maintenance Therapy in Patients With PIK3CA Mutated Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT03386162
- Acronym / sponsor ID
- SAFIR-PI3K / UC-0105/1701
- Conditions
- Breast Cancer, PI3K, Alpelisib
- Keywords
- Breast cancer, PI3K, alpelisib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was halted Prematurely for low recruitment.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 18 Nov 2022 (actual)
- Study completion
- 18 Nov 2022 (actual)
- First posted
- 29 Dec 2017 (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.
SAFIR PI3K is an open-label multicenter phase II randomized trial, comparing alpelisib plus fulvestrant to maintenance chemotherapy in patient PIK3CA mutated with HR+/Her2- metastatic breast cancer who do not present progressive disease after 6-8 cycles of 1st or second line chemotherapy.
The primary objective is to determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to maintenance chemotherapy in patients PIK3CA mutated with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who do not present a progressive disease after 6-8 cycles of chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In the randomized treatment phase, patients will be randomized 2:1 to receive: • Experimental arm (Arm A3): fulvestrant (500 mg intramuscular [as two 5 mL injections] every 28 days ± 3 days, with an additional injection on 15 after the first administration + Alpelisib (300 mg by mouth once daily, in a 21-day cycle). Premenopausal women will receive luteinizing hormone-releasing hormone (LH-RH) analogs in addition every 28 days ± 3 days. OR • Control arm (Arm B3): maintenance chemotherapy, meaning the same chemotherapy regimen used during the first 6-8 cycles (investigator's choice) or no antineoplastic treatment in case of toxicity after 4 full cycles. A total of approximately 90 patients will be enrolled
| Arm | Type | Receives |
|---|---|---|
| Experimental arm (Arm A3) | Experimental | Drug: Alpelisibfulvestrant (500 mg intramuscular [as two 5 mL injections] every 28 days ± 3 days, with an additional injection on 15 after the first administration + Alpelisib (300 mg by mouth once daily, in a 21-day cycle). Premenopausal women will receive LH-RH analogs in addition every 28 days ± 3 days. |
| Control arm (Arm B3) | Active comparator | Drug: Chemotherapymaintenance chemotherapy, meaning the same chemotherapy regimen used during the first 6-8 cycles (investigator's choice) or no antineoplastic treatment in case of toxicity after 4 full cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Women (or men) with histologically confirmed metastatic breast cancer.
- Hormone receptor positive (HR+) and no Her2 over-expression, according to local assessment.
- Presence of PIK3CA mutation on exon 9 or 20, determined on metastatic tissue specimen (frozen or FFPE) or plasma (ctDNA). Eligible plasma should have been collected at time of metastatic disease progression and before to initiating chemotherapy.
- Patient's disease is resistant to endocrine therapy (defined either as a relapse or progression occurred during endocrine therapy, whatever the line, or less than 12 months after the end of endocrine therapy in adjuvant context).
- Patients who received 6 to 8 cycles of a first line chemotherapy, or patients who received 6 to 8 cycles of a first line stopped for progression followed by 6 to 8 cycles of a 2nd line chemotherapy, and who are presenting a stable or a responding disease at the time of randomization (4 full cycles of chemotherapy are accepted if stopped for toxicity reasons)
Key exclusion criteria (37 listed)
- Spinal cord compression or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable without steroids during the last 30 days).
- Patient has received more than 2 previous lines of chemotherapy for metastatic disease before randomization.
- Prior exposure to anthracyclines or mitoxantrone with cumulative exposure in excess of 360 mg/m² for doxorubicin, 720 mg/m² for epirubicin, or 72 mg/m² for mitoxantrone.
- In the Investigator's judgment, patient has a life expectancy <3 months .
- Disease progression occuring before randomization.
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 |
|---|---|---|
| AlpelisibAlso: fulvestrantfulvestrant (500 mg intramuscular [as two 5 mL injections] every 28 days ± 3 days, with an additional injection on 15 after the first administration + Alpelisib (300 mg by mouth once daily, in a 21-day cycle). Premenopausal women will receive LH-RH analogs in addition every 28 days ± 3 days. | Drug | Experimental arm (Arm A3) |
| Chemotherapymaintenance chemotherapy, meaning the same chemotherapy regimen used during the first 6-8 cycles (investigator's choice) or no antineoplastic treatment in case of toxicity after 4 full cycles. | Drug | Control arm (Arm B3) |
Primary outcome
progression-free survival
Time frame: 6 months
To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to maintenance chemotherapy in patients PIK3CA mutated with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who do not present a progressive disease after 6-8 cycles of chemotherapy.
Results and safety
The study was stopped early (reason given: Study was halted Prematurely for low recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2022.
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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.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alpelisib and Chemotherapy in people with Breast Cancer, PI3K, Alpelisib, run by UNICANCER at 14 sites in France.
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 22 inclusion and 37 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: stopped early, as of the sponsor's last update on 28 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in France. 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?
The study was stopped early (reason given: Study was halted Prematurely for low recruitment.). 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?
progression-free survival (time frame: 6 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 28 Nov 2022.