Trastuzumab + Alpelisib +/- Fulvestrant vs Trastuzumab + CT in Patients With PIK3CA Mutated Previously Treated HER2+ Advanced BrEasT Cancer (ALPHABET)

Sponsor
Spanish Breast Cancer Research Group
Study ID
NCT05063786
Phase
PHASE3
Status
Active Not Recruiting

Conditions

  • Advanced Breast Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Trastuzumab — BIOLOGICAL
    6 mg/kg IV every 3 weeks (3-weekly schedule), or 4 mg/kg IV loading dose, followed by 2mg/kg IV weekly (weekly schedule)\*, or 600 mg SC every 3 weeks. \* If using trastuzumab IV, a loading dose of 8 mg/kg (for the 3-weekly schedule), or 4 mg/kg (for the weekly schedule) is necessary if more than 6 weeks have passed since the previous trastuzumab dose.
  • Alpelisib — DRUG
    300 mg oral once daily.
  • Fulvestrant — DRUG
    500 mg intramuscular every 4 weeks plus loading dose on day 15 cycle 1.
  • Vinorelbine — DRUG
    Oral (60 mg/m2) or IV (25 or 30 mg/m2 per investigator preference) on days 1 and 8, every 3 weeks.
  • Capecitabine — DRUG
    1250 or 1000 mg/m2 (per investigator preference) twice a day (BID) oral, 2 weeks on, 1 week off, every 3 weeks.
  • Eribulin — DRUG
    1.23 mg/m2 IV on days 1 and 8, every 3 weeks.

Study Details

Randomized phase III trial of trastuzumab + Alpelisib +/- fulvestrant versus trastuzumab + chemotherapy in patients with PIK3CA mutated previously treated HER2+ Advanced Breast cancer.

Key Dates

Start date
Sep 14, 2021
Status verified
Sep 2025
Primary completion
Jun 30, 2026
Completion
Jun 30, 2026

Study Design

Enrollment
27 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental Arm (Arm A) Cohort 1 (HER2+/HR-)
    Trastuzumab either intravenous (IV) or subcutaneous (SC): 6 mg/kg IV every 3 weeks (3-weekly schedule), or 2 mg/kg IV weekly (weekly schedule)\*, or 600 mg SC every 3 weeks. Alpelisib 300 mg oral once daily. \*If using trastuzumab IV, a loading dose of 8 mg/kg (for the 3-weekly schedule), or 4 mg/kg (for the weekly schedule) is necessary if more than 6 weeks have passed since the previous trastuzumab dose.
  • Experimental: Experimental Arm (Arm A) Cohort 2 (HER2+/HR+)
    Trastuzumab either intravenous (IV) or subcutaneous (SC): 6 mg/kg IV every 3 weeks (3-weekly schedule), or 2 mg/kg IV weekly (weekly schedule)\*, or 600 mg SC every 3 weeks. Alpelisib 300 mg oral once daily. Fulvestrant 500 mg intramuscular every 4 weeks plus loading dose on day 15 cycle 1. Males and females who are not post-menopausal must have been on a gonadotropin-releasing hormone (GnRH) agonist (e.g. goserelin or leuprorelin) for at least 28 days prior to starting study treatment, and should continue with this therapy. \*If using trastuzumab IV, a loading dose of 8 mg/kg (for the 3-weekly schedule), or 4 mg/kg (for the weekly schedule) is necessary if more than 6 weeks have passed since the previous trastuzumab dose.
  • Active Comparator: Control Arm (Arm B ) Cohorts 1 and 2
    Trastuzumab either intravenous (IV) or subcutaneous (SC): 6 mg/kg IV every 3 weeks (3-weekly schedule), or 2 mg/kg IV weekly (weekly schedule)\*, or 600 mg SC every 3 weeks. Chemotherapy (CT): vinorelbine, capecitabine or eribulin (according to investigator preference): * Vinorelbine either oral (60 mg/m2) or IV (25 or 30 mg/m2 per investigator preference) on days 1 and 8, every 3 weeks. * Capecitabine: 1250 or 1000 mg/m2 (per investigator preference) twice a day (BID) oral, 2 weeks on, 1 week off, every 3 weeks. * Eribulin: 1.23 mg/m2 IV on days 1 and 8, every 3 weeks. * If using trastuzumab IV, a loading dose of 8 mg/kg (for the 3-weekly schedule), or 4 mg/kg (for the weekly schedule) is necessary if more than 6 weeks have passed since the previous trastuzumab dose.

Primary Outcome Measure

Progression Free Survival (PFS) [ Time Frame: The accumulation of targeted PFS events is estimated at 44 and 38 months since first patients randomized, in the HR- and HR+ cohorts, respectively. ]

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