Breast Cancer Clinical Trial
Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutation With Advanced Breast Cancer Who Have Progressed on or After Prior Treatments
Summary
Study assessing the efficacy and safety of alpelisib plus fulvestrant or letrozole, based on prior endocrine therapy, in patients with PIK3CA mutation with advanced breast cancer who have progressed on or after prior treatments
Full Description
This is a phase II, multicenter, open-label, three-cohort, noncomparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in patients with HR+, HER2-negative aBC harboring PIK3CA mutation(s) in the tumor whose disease has progressed on or after prior treatments.
The study includes two phases:
Core Phase: Includes treatment phase for all patients from First Patient First Treatment (FPFT) until 18 months post Last Patient First Treatment (LPFT) + 1 month Safety follow-up (total 19 months post LPFT) Extension Phase: includes treatment phase starting at the end of the treatment Core Phase until 12 months. The extension treatment phase is only for patients who are continuing to benefit from treatment at the end of the Core Phase and are not eligible for PSDS (Post-Study Drug Supply) in their country based on local regulations. Patients will continue on their existing treatment assigned in the Core Phase. If PSDS becomes available for a patient, the patient should be discontinued from the study and access treatment via PSDS.
Patients who are benefiting from treatment and are eligible for PSDS will exit the trial at the end of the Core Phase.
Eligibility Criteria
Inclusion Criteria:
Patient is male or female 18 years or older
Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer not amenable to curative therapy
In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant
Patient is postmenopausal woman defined as either:
Prior bilateral oophorectomy or
Age ≥60 or
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.
If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.
Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status
Patient is premenopausal defined as either:
Patient had last menstrual period within the last 12 months or
If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
Patient has confirmed HER2-negative advanced breast cancer (aBC)
Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
Patient must have:
Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,
AI treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET(as monotherapy or in combination except CDK 4/6i + AI) as last treatment regimen in cohort C
Maintenance therapies, where applicable, must be regarded as part of the main treatment.
No more than two (2) prior anti-cancer therapies for aBC
Received no more than one prior regimen of chemotherapy in the metastatic setting
Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present
ECOG performance status ≤ 2
Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)
Patient has adequate bone marrow, coagulation, liver and renal function
Exclusion Criteria:
patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
Patient has received prior treatment with any PI3K inhibitors
Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II
Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer
Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
Patient with severe liver impairment (Child Pugh score B/C)
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
Patient has documented pneumonitis/interstitial lung disease which is active and requiring treatment
Patient has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necroloysis (TEN) or Drug Reaction with Eosinphilia and Systemic Symptoms (DRESS).
Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.
Subjects with unresolved osteonecrosis of the jaw.
Other inclusion/exclusion criteria may apply
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There are 92 Locations for this study
Gilbert Arizona, 85234, United States
Phoenix Arizona, 85054, United States
Anaheim California, 92807, United States
Beverly Hills California, 90211, United States
Orange California, 92868, United States
San Diego California, 92120, United States
San Francisco California, 94115, United States
New Haven Connecticut, 06511, United States
Orlando Florida, 32804, United States
Kansas City Kansas, 66205, United States
Louisville Kentucky, 40202, United States
Baltimore Maryland, 21202, United States
Baltimore Maryland, 21204, United States
Boston Massachusetts, 02114, United States
Burlington Massachusetts, 01805, United States
Detroit Michigan, 48202, United States
Billings Montana, 59102, United States
Albuquerque New Mexico, 87106, United States
New York New York, 10065, United States
Cleveland Ohio, 44106, United States
Dallas Texas, 75246, United States
San Antonio Texas, 78229, United States
San Antonio Texas, 78229, United States
Norfolk Virginia, 23502, United States
Tacoma Washington, 98405, United States
Caba Buenos Aires, C1118, Argentina
Caba Buenos Aires, C1125, Argentina
Caba Buenos Aires, C1426, Argentina
Rosario Santa Fe, S2000, Argentina
Rosario Sante Fe, S200K, Argentina
La Rioja , 5300, Argentina
Leuven , 3000, Belgium
Liege , 4000, Belgium
Vancouver British Columbia, V5Z 4, Canada
Halifax Nova Scotia, B3H 2, Canada
Kitchener Ontario, N2G 1, Canada
Toronto Ontario, M5B 1, Canada
Temuco Araucania, 48104, Chile
Santiago , 75009, Chile
Santiago , 84203, Chile
Odense C , DK 50, Denmark
Vejle , 7100, Denmark
Nice Cedex 2 Alpes Maritimes, 06189, France
Saint-Cloud Hauts De Seine, 92210, France
Bordeaux , 33076, France
Caen Cedex , 14021, France
Lille Cedex , 59020, France
Lyon Cedex , 69373, France
Montpellier Cedex 5 , 34298, France
Saint Herblain cedex , 44805, France
Strasbourg Cedex , F 670, France
Toulouse Cedex 9 , 31059, France
Augsburg , 86150, Germany
Berlin , 14169, Germany
Dresden , 01307, Germany
Erlangen , 91054, Germany
Essen , 45136, Germany
Heidelberg , 69120, Germany
Ulm , 89081, Germany
Delhi , 110 0, India
Petach Tikva , 49414, Israel
Ramat Gan , 52621, Israel
Rehovot , 76100, Israel
Tel Aviv , 64239, Israel
Ancona AN, 60126, Italy
Bergamo BG, 24127, Italy
Bologna BO, 40138, Italy
Genova GE, 16132, Italy
Milano MI, 20133, Italy
Milano MI, 20141, Italy
Roma RM, 00168, Italy
Napoli , 80131, Italy
Osaka-city Osaka, 540-0, Japan
Seoul , 03080, Korea, Republic of
Seoul , 06351, Korea, Republic of
Jalisco , 45640, Mexico
Maastricht AZ, 5800, Netherlands
Singapore , 16961, Singapore
Singapore , 21756, Singapore
Sevilla Andalucia, 41013, Spain
Salamanca Castilla Y Leon, 37007, Spain
Barcelona Catalunya, 08035, Spain
Barcelona Catalunya, 08036, Spain
Hospitalet de LLobregat Catalunya, 08907, Spain
Castellon Comunidad Valenciana, 12002, Spain
Madrid , 28041, Spain
Tainan , 70403, Taiwan
Taipei , 10002, Taiwan
Taipei , , Taiwan
Sutton Surrey, SM2 5, United Kingdom
Edinburgh , EH4 2, United Kingdom
Leicester , LE1 5, United Kingdom
London , SW3 6, United Kingdom
Nottingham , NG5 1, United Kingdom
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