Phase II, Multicenter, Single Arm Trial to Assess the Feasibility of First Line Ribociclib in Combination with a Non Steroidal Aromatase Inhibitor in Elderly Patients with Hormone Receptor Positive/HER2 Negative Advanced Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Ribociclib
- Conditions
- Breast Cancer
- Sponsor
- Fondazione Sandro Pitigliani
- Enrollment
- 116
- Locations
- 1
- Primary Endpoint
- Treatment feasibility
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
Phase II, multicenter, single arm trial to assess the feasibility of first line ribociclib in combination with a non steroidal aromatase inhibitor in women or men aged 70 years-old or older, with hormone receptor positive/HER2 negative advanced breast cancer
Detailed Description
Elderly patients are generally more susceptible to the side effects of active treatments. Patients entered in clinical trials, especially the elderly, are not completely representative of the "real" population because of selection process. The lack of data collected from a real population turns the indication of treatment a challenging task and expose older patients to a risk of under treatment (fear of excessive toxicity because of the lack of data). With the aim of covering this gap, we are planning to run a phase II trial evaluating the feasibility of delivering the combination of ribociclib plus NSAI as first-line treatment specifically in a population of breast cancer patients aged ≥70 years. Primary endpoint: • The treatment feasibility will be evaluated as the proportion of patients not having experienced disease progression (PD), still on treatment with ribociclib plus NSAI 6 months after the first drug administration Secondary endpoints: * Treatment adherence * Safety and tolerability * Patient reported outcomes (PROs) * Overall response rate (ORR) * Progression free survival (PFS)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients male or female, aged 70 years-old or older at the time of informed consent.
- •Patients with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
- •Measurable or not measurable but evaluable disease according to RECIST criteria 1.1
- •Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
- •Patient has a HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
- •Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patient has an estimated life expectancy of \> 24 weeks.
- •Patient has adequate bone marrow and organ function as defined by all of the following laboratory values (as assessed by local laboratory):
- •Absolute neutrophil count ≥1.5 x 109/L
- •Platelets ≥ 100 x 109/L
Exclusion Criteria
- •Patient has received prior treatment with chemotherapy or hormonal therapy (except for neoadjuvant/ adjuvant chemotherapy), or any CDK4/6 inhibitor.
- •Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease-free interval must be greater than 12 months from the completion of treatment until study entry.
- •Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
- •Patient has a known hypersensitivity to any of the excipients of ribociclib or NSAI
- •Patient in concurrently using other anti-cancer therapy.
- •Patient who has not had resolution of all acute toxic effects of prior anti-cancer therapy to NCI CTCAE version 5.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
- •Patient who has received extended-field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to start of treatment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patient from whom ≥ 25% of the bone marrow has been previously irradiated are also excluded
- •Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- •Patient with central nervous system (CNS) metastases unless they meet all of the following criteria:
- •At least 4 weeks from prior therapy for CNS disease completion (including radiation and/or surgery) to starting the study treatment.
Arms & Interventions
single arm
patients will receive anastrozole tablets (1 mg once daily) or letrozole tablets (2.5 mg once daily) + ribociclib tablets (600 mg day 1 to 21 in a 28 day cycle). Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, physician's decision, patient's refusal/consent withdrawal, or lost to follow-up. A LHRH agonist (triptorelin 3,75 mg or leuprolide 3,75 mg or goserelin 3,6 mg, as injectable intramuscular (i.m.) or subcutaneous (s.c.) implant every 28 days) will be used in men.
Intervention: Ribociclib
single arm
patients will receive anastrozole tablets (1 mg once daily) or letrozole tablets (2.5 mg once daily) + ribociclib tablets (600 mg day 1 to 21 in a 28 day cycle). Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, physician's decision, patient's refusal/consent withdrawal, or lost to follow-up. A LHRH agonist (triptorelin 3,75 mg or leuprolide 3,75 mg or goserelin 3,6 mg, as injectable intramuscular (i.m.) or subcutaneous (s.c.) implant every 28 days) will be used in men.
Intervention: Aromatase Inhibitors, non steroideal
single arm
patients will receive anastrozole tablets (1 mg once daily) or letrozole tablets (2.5 mg once daily) + ribociclib tablets (600 mg day 1 to 21 in a 28 day cycle). Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, physician's decision, patient's refusal/consent withdrawal, or lost to follow-up. A LHRH agonist (triptorelin 3,75 mg or leuprolide 3,75 mg or goserelin 3,6 mg, as injectable intramuscular (i.m.) or subcutaneous (s.c.) implant every 28 days) will be used in men.
Intervention: LHRH agonist
Outcomes
Primary Outcomes
Treatment feasibility
Time Frame: 6 months
The treatment feasibility will be evaluated as the proportion of patients not having experienced disease progression (PD), still on treatment with ribociclib plus NSAI 6 months after the first drug administration
Secondary Outcomes
- Progression free survival (PFS)(36 months)
- Patient Diary(36 months)
- Incidence of Treatment-Emergent adverse events and serious adverse events (Safety and tolerability)(36 months)
- Patient reported outcomes (PROs)(36 months)
- Overall response rate (ORR)(36 months)
- Number of comorbities (impact on study inclusion)(30 months)