SAFIR-PI3K A Phase II Randomized Maintenance Trial Comparing Alpelisib and Fulvestrant Versus Chemotherapy in PIK3CA Mutated Advanced Breast Cancer

NCT03386162 | Terminated Phase 2 DMC

• 1 other identifier: UC-0105/1701
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 14

Brief 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. 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

Keywords

Breast cancer, PI3K, alpelisib

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Study Arms (2)

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.

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.

Drug: Chemotherapy

Interventions

Alpelisib DRUG

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.

Also known as: fulvestrant

Experimental arm (Arm A3)

Chemotherapy DRUG

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.

Control arm (Arm B3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (14)

Institut de Cancérologie de l'Ouest/Paul Papin

Angers, France

Location

Institut Sainte-Catherine

Avignon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Chd Vendee

La Roche-sur-Yon, France

Location

CHU Dupuytren

Limoges, France

Location

Centre Leon Berard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

CInstitut Regional du cancer-Centre Val D'Aurelle

Montpellier, France

Location

Centre Eugène Marquis

Rennes, France

Location

Centre Rene Huguenin

Saint-Cloud, 92211, France

Location

Hôpitaux du Léman

Thonon-les-Bains, 74200, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Breast Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Interventions

Alpelisib; Fulvestrant; Drug Therapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: December 29, 2017
• Study Start: March 15, 2018
• Primary Completion: November 18, 2022
• Study Completion: November 18, 2022
• Last Updated: November 28, 2022

Record last verified: 2022-11

Locations

FR (14)