BridgeMD
Endocrine therapy plus CDK 4/6 inhibition in first- or second-line for hormone receptor positive advanced breast cancer - the SONIA study
EU CTIS ID: 2024-516204-42-00
What this study is testing
To evaluate if treatment with a non-steroidal aromatase inhibitor combined with CDK4/6 inhibition in first line followed at progression by fulvestrant in second line (strategy A) improves progression-free survival compared to treatment with a non-steroidal aromatase inhibitor in first line followed at progression by fulvestrant combined with CDK4/6 inhibition in second line (strategy B) in women with HR+/HER2- metastatic breast cancer who have not received any prior systemic anticancer therapy for metastatic disease.
- Therapeutic confirmatory (Phase III)
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 (≥ 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
- Documentation of histologically or cytologically 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-negative as defined by ASCO-CAP guidelines (9). If HER2 status is unavailable then testing must be performed/repeated prior to randomization.
- Previously untreated with any systemic anti-cancer therapy for metastatic HR+ disease, with the exception of recently started (within 28 days of randomization) endocrine therapy.
- Women who are not post-menopausal must receive ovarian ablation or suppression with administration of LHRH agonist.
- Evaluable disease as defined per RECIST v.1.1. 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.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
You likely can't join if
- Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% liver involvement).
- Known hypersensitivity to letrozole or anastrozole, or any of its excipients, or to any CDK4/6 inhibitors excipients.
- 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 randomization
- Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (i.e. anastrozole or letrozole) with disease recurrence while on or within 12 months of treatment.
- Prior treatment with any CDK4/6 inhibitor.
- Patients treated within the last 7 days prior to randomization with: 1) Food or drugs that are known to be CYP3A4 inhibitors (ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit, pomegranate or grapefruit/pomegranate juice); 2) Drugs that are known to be CYP3A4 inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St. John’s wort).
See the full eligibility criteria
Who can join
- Adult women (≥ 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
- Documentation of histologically or cytologically 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-negative as defined by ASCO-CAP guidelines (9). If HER2 status is unavailable then testing must be performed/repeated prior to randomization.
- Previously untreated with any systemic anti-cancer therapy for metastatic HR+ disease, with the exception of recently started (within 28 days of randomization) endocrine therapy.
- Women who are not post-menopausal must receive ovarian ablation or suppression with administration of LHRH agonist.
- Evaluable disease as defined per RECIST v.1.1. 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.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
- Adequate organ and marrow function defined as follows: 1) ANC ≥1,000/mm3 (1.0 x 10e9 /L); 2) Platelets ≥50,000/mm3 (50 x 10e9 /L); 3) Estimated creatinine clearance ≥ 30 mL/min as calculated using the method standard for the institution; 4) Total serum bilirubin ≤1.5 x ULN (≤3.0 x ULN if Gilbert’s disease); 5) AST and ALT ≤3 x ULN (≤5.0 x ULN if liver metastases present);
- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤1, except alopecia or 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 (including patients with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50% liver involvement).
- Known hypersensitivity to letrozole or anastrozole, or any of its excipients, or to any CDK4/6 inhibitors excipients.
- 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 randomization
- Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (i.e. anastrozole or letrozole) with disease recurrence while on or within 12 months of treatment.
- Prior treatment with any CDK4/6 inhibitor.
- Patients treated within the last 7 days prior to randomization with: 1) Food or drugs that are known to be CYP3A4 inhibitors (ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine, diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit, pomegranate or grapefruit/pomegranate juice); 2) Drugs that are known to be CYP3A4 inducers (ie, carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and St. John’s wort).
- Major surgery, chemotherapy, any investigational agents, or other anticancer therapy within 2 weeks before randomization. Palliative radiotherapy and/or (neo)adjuvant endocrine treatment within 2 weeks before randomization are allowed, provided that patients have recovered from these treatments. Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible independent of when it was received.
- Diagnosis of any other malignancy prior to randomization, except those that are not believed to influence the patient’s 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.
- QTc >480 msec at baseline
- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery that influences uptake of oral medication
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 female, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
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.