Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Fulvestrant + Metronomic Capecitabine (continuous low-dose) CDK4/6 inhibitor: Fulvestrant 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1,and then on Day 1, Week
patients more than equal to 60 kg receive 2000 mg daily (1000 mg twice daily) and Investigators have the option to add a CDK4/6 inhibitor.
Control Intervention1: Fulvestrant alone with Investigator ch
Sponsors
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Eligibility
Inclusion criteria
Inclusion criteria: Age above 18 years. Histologically confirmed HR+/HER2- breast cancer with metastatic and/or unresectable locally advanced disease. HR+ is defined as estrogen receptor and/or progesterone receptor expression in more than or equal to 1 percent of tumor nuclei by IHC. HER2-negative is defined per ASCO/CAP guidelines (IHC 0 1+ or IHC2+ with FISH non-amplified). Postmenopausal women, or premenopausal women if rendered functionally postmenopausal (e.g., on ovarian suppression with an LHRH agonist). Fulvestrant is indicated for postmenopausal hormone receptor positive patients; thus, premenopausal patients must agree to concurrent ovarian function suppression. Male patients with HR+/HER2- mBC may be included (with appropriate hormonal therapy, e.g., GnRH analog, if needed), although the incidence is expected to be low. Prior Endocrine Therapy: Patients may have received up to one line of prior endocrine therapy for metastatic disease or have relapsed during/within 12 months of completion of adjuvant endocrine therapy. Rationale: Many patients will have progressed on an aromatase inhibitor (AI) or tamoxifen before needing fulvestrant. If no prior ET for mBC, the patient should have a contraindication or intolerance to AIs or have relapsed Less than twelvemonths after adjuvant AI (warranting fulvestrant as reasonable first-line). CDK4/6 Inhibitor status: Prior CDK4/6 inhibitor therapy is allowed but not required. Patients who have not received a CDK4/6 inhibitor are eligible and may receive one in this trial as per the investigator s plan. Patients who have progressed on a prior CDK4/6 inhibitor are also eligible; in such cases, adding a CDK4/6 inhibitor in this trial will depend on the feasibility of utilizing ribociclib (as per the MAINTAIN trial results, showing some benefit of continuing ribociclib or transitioning from palbociclib to ribociclib on progression)[15]. Prior Chemotherapy: Use of prior chemotherapy in metastatic settings is not allowed, unless it was started in view of visceral crisis/other situations deemed necessary by the treating oncologist, provided it was utilized only for a short duration (not more than 2 months, and the patient has not progressed on the same). Prior neoadjuvant/adjuvant chemotherapy is permitted if it was more than 12 months before metastatic recurrence. Patients who received prior capecitabine (in adjuvant or metastatic settings) may be excluded unless it was completed More than months ago with no severe toxicity this is to ensure we are not re-challenging recent capecitabine-refractory disease. (Prior use of other 5-FU or cytotoxics is allowed with caution). These cases should be discussed with the lead PI/co-PI to ensure the suitability of the inclusion of such patients. Measurable or evaluable disease as per RECIST 1.1. (Measurable disease is not strictly required; patients with bone-only metastases, for example, are eligible and will be assessed by bone scan and CT/PET CT for progression.) Visceral vs. non-visceral disease: Both patients with visceral metastases (e.g., liver, lung) and those with only bone/soft tissue metastases are eligible. This will be a stratification factor. Patients with brain metastases are eligible if neurologically stable after treatment and not requiring corticosteroids at the time of randomization. Performance status: ECOG performance status 0 1 (fully active or restricted in heavy activity but ambulatory and able to
Exclusion criteria
Exclusion criteria: HER2-positive breast cancer (IHC 3+ or FISH amplified). Prior treatment with fulvestrant for advanced/metastatic breast cancer with documented disease progression. Receipt of chemotherapy, targeted therapy, investigational agents, or other anti-cancer therapy within 2 weeks prior to randomization (4 weeks for monoclonal antibodies and 6 weeks for nitrosoureas or mitomycin C), or unresolved treatment-related toxicities greater than Grade 1 (except alopecia). Symptomatic or uncontrolled central nervous system (CNS) metastases, leptomeningeal disease, or brain metastases requiring ongoing corticosteroid therapy. Significant uncontrolled comorbid conditions, including but not limited to: Recent myocardial infarction or unstable angina New York Heart Association (NYHA) Class III/IV heart failure Uncontrolled infection Severe hepatic impairment or Child-Pugh Class B/C liver disease Any serious medical condition that may interfere with study participation. Pregnant or breastfeeding women. Women of childbearing potential unwilling to use adequate contraception during study participation. Known hypersensitivity or contraindication to fulvestrant, capecitabine, fluorouracil (5-FU), or any planned CDK4/6 inhibitor. Presence of another active malignancy requiring treatment, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or other malignancies considered cured and not requiring active therapy. Any psychological, familial, sociological, or geographical condition that, in the opinion of the investigator, may compromise compliance with the study protocol. Inability or unwillingness to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS), assessed from randomization until disease progression per RECIST v1.1 or death from any cause.Timepoint: Assessed every 8 weeks during the first 6 months, then every 12 weeks thereafter until disease progression, death, or study completion(approximately 4 years). | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) Objective Response Rate (ORR) Clinical Benefit Rate (CBR) Time to Second Progression (PFS2) Chemotherapy-Free Survival (CFS) Safety and Tolerability (CTCAE v5.0) Quality of Life (EORTC QLQ-C30 and BPI-SF)Timepoint: Assessed every 3 months after treatment discontinuation until death or study completion (approximately 4 years). Assessed every 8 weeks for the first 6 months, then every 12 weeks until progression. Evaluated at 24 weeks after randomization and throughout treatment. Assessed until second progression, death, or study completion (approximately 4 years). Assessed until initiation of subsequent chemotherapy, death, or study completion (approximately 4 years). Continuously from first dose until 30 days after last study treatment. At baseline, Month 3 ( 15 days), and at disease progression. | — |
Countries
India
Contacts
Public ContactDr Anuj Gupta
Mahamana Pandit Madan Mohan Malaviya Cancer Centre
Outcome results
None listed