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SEQUEL-Breast: a phase 2 study on the combination of alpelisib and fulvestrant after progression on previous therapy with fulvestrant in patients with PIK3CA-mutated, hormone-receptor positive, HER2 negative advanced breast cancer
EU CTIS ID: 2024-514965-20-00
What this study is testing
To investigate the efficacy of the combination of fulvestrant and alpelisib directly after progression on 1st or 2nd line therapy with fulvestrant (monotherapy or in combination with a CDK 4/6 inhibitor) in pre- or postmenopausal women and men with HR+HER2- advanced breast cancer with tumors harboring an activating PIK3CA mutation. Previous treatment with a CDK 4/6 inhibitor (either in 1st or 2nd line) is mandatory.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Adult women and men 18 years of age) with proven diagnosis of adenocarcinoma of the breast with locoregional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated. Women must be postmenopausal, have had a bilateral oophorectomy, or receive an luteinizing hormone releasing hormone (LHRH)analogue. Men must receive an LHRH-analogue.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study before any study-specific activity is performed.
- Documentation of histologically confirmed diagnosis of estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer based on local laboratory results. In case ER 10% and PR >10% the ER and PR expression need to be confirmed in a referral center. Tumor must be HER2- as defined by ASCO-CAP guidelines. If HER2 status is unavailable then testing must be performed/repeated.
- Patients must have progressed on fulvestrant as a preceding treatment line (as first or second line therapy). In case of fulvestrant discontinuation, this discontinuation has not exceeded 12 weeks. In case fulvestrant plus a CDK4/6 inhibitor has been given in 1st line as last treatment, the patient must have progressed during or shortly (<12 months) after stopping adjuvant treatment with an (NS)AI.
- Previous treatment with a CDK4/6 inhibitor in the advanced setting is mandatory.
You likely can't join if
- Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in the short term (visceral crisis), e.g. patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and >50% liver involvement
- Known allergy for alpelisib or fulvestrant or previous unacceptable toxicity during treatment with fulvestrant.
- Clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following: History of documented congestive heart failure (New York Heart Association functional classification III-IV); Clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place; Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or Fridericia QT correction formula (QTcF) > 470 msec at screening (mean of triplicate ECGs); Any recent cardiac events that would -in the opinion of the treating clinician- potentially intervene with study treatment.
- Current use of any of the following medications and these medications cannot be discontinued 7 days prior to the start of the treatment: Strong CYP3A4 inducers Inhibitors of BCRP See appendix B for forbidden co-medications.
- For women: pregnancy. For sexually active males: unwillingness to take precautions to make sure they do not inseminate.
- Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the clinician or investigator, would make the patient inappropriate for entry into this study, include, but are not limited to: - History of severe cutaneous reactions, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); - History of pancreatitis; - Unresolved osteonecrosis of the jaw; - Severe cases of auto-immune disease; - Clinically relevant pneumonitis; - Suicidal ideations / suicidal behavior.
See the full eligibility criteria
Who can join
- Adult women and men 18 years of age) with proven diagnosis of adenocarcinoma of the breast with locoregional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated. Women must be postmenopausal, have had a bilateral oophorectomy, or receive an luteinizing hormone releasing hormone (LHRH)analogue. Men must receive an LHRH-analogue.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study before any study-specific activity is performed.
- Documentation of histologically confirmed diagnosis of estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer based on local laboratory results. In case ER 10% and PR >10% the ER and PR expression need to be confirmed in a referral center. Tumor must be HER2- as defined by ASCO-CAP guidelines. If HER2 status is unavailable then testing must be performed/repeated.
- Patients must have progressed on fulvestrant as a preceding treatment line (as first or second line therapy). In case of fulvestrant discontinuation, this discontinuation has not exceeded 12 weeks. In case fulvestrant plus a CDK4/6 inhibitor has been given in 1st line as last treatment, the patient must have progressed during or shortly (<12 months) after stopping adjuvant treatment with an (NS)AI.
- Previous treatment with a CDK4/6 inhibitor in the advanced setting is mandatory.
- The presence of an activating PIK3CA mutation; preferably detected in a metastasis as PIK3CA mutation status may change during the course of the disease. In case a biopsy from a metastasis is not obtainable, mutation analysis may be performed on the primary tumor or archival tumor material.
- Evaluable disease* as defined per RECIST v.1.1 (Eisenhauer et al, 2009). Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented. * Evaluable disease in this study is defined as measurable and non-measurable disease according to RECIST, with the exception of truly non-measurable disease only (i.e. ascites or pleural effusion as only site of disease). In case of truly non-measurable disease only, a patient is NOT considered evaluable according to RECIST. Bone-only disease is considered evaluable.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2.
- Adequate organ and marrow function defined as follows: a) ANC 1.0 x 10e9 /L; b) Platelets 75 x 10e9 / L; c) Estimated creatinine clearance 30 mL/min as calculated using the method standard for the institution; d) Total serum bilirubin ≤3x ULN (≤5x ULN if Gilbert's disease); e) ASAT and ALAT ≤3x ULN (≤5x ULN if liver metastases present)
- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.03 Grade except other toxicities not considered a safety risk for the patient at investigator's discretion.
What rules you out
- Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in the short term (visceral crisis), e.g. patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and >50% liver involvement
- Known allergy for alpelisib or fulvestrant or previous unacceptable toxicity during treatment with fulvestrant.
- Clinically significant, uncontrolled heart disease and/or recent cardiac events including any of the following: History of documented congestive heart failure (New York Heart Association functional classification III-IV); Clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia), complete left bundle branch block, high grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place; Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or Fridericia QT correction formula (QTcF) > 470 msec at screening (mean of triplicate ECGs); Any recent cardiac events that would -in the opinion of the treating clinician- potentially intervene with study treatment.
- Current use of any of the following medications and these medications cannot be discontinued 7 days prior to the start of the treatment: Strong CYP3A4 inducers Inhibitors of BCRP See appendix B for forbidden co-medications.
- For women: pregnancy. For sexually active males: unwillingness to take precautions to make sure they do not inseminate.
- Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the clinician or investigator, would make the patient inappropriate for entry into this study, include, but are not limited to: - History of severe cutaneous reactions, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); - History of pancreatitis; - Unresolved osteonecrosis of the jaw; - Severe cases of auto-immune disease; - Clinically relevant pneumonitis; - Suicidal ideations / suicidal behavior.
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable without the use of steroids for at least 4 weeks before enrollment.
- Prior treatment with an PI3K /AKT/mTOR inhibitor
- Prior treatment with chemotherapy in the advanced setting.
- (Prior) use of oral SERD in any setting
- Type 1 diabetes or uncontrolled type 2 diabetes. Type 2 diabetes is deemed uncontrolled when the Hba1C at screening exceeds 68 mmol/mol.
- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection.
- Major surgery, any investigational agents, or other anticancer therapy within 2 weeks before enrollment.
- Diagnosis of any other malignancy prior to enrollment, except those that are not believed to influence the prognosis and do not require any further treatment. This includes but is not limited to adequately treated basal cell or squamous cell skin cancer and carcinoma in situ of the cervix.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.