SETHY is a prospective, multicohort, phase II, single-arm, non-randomized, non-blinded, investigator-initiated study of sacituzumab govitecan in patients with advanced or metastatic radioactive-iodine refractory differentiated thyroid carcinoma (DTC) or anaplastic thyroid carcinoma (ATC). The main hypothesis is that treatment with sacituzumab govitecan, a anti-Trophoblast cell surface antigen 2 (TROP-2), could be an effective treatment option for patients with either differentiated and anaplastic thyroid neoplasms because TROP-2 is highly expressed at the membrane of DTC and ATC.
The trial will enroll competitively up to 21 patients per cohort. The study will enroll the first 12 patients within the cohort and monitor for response. If no confirmed response is documented the cohort will be closed. If there is one or more confirmed responses reported that cohort will be expanded up to the expected 21 patients. All patients, male or female, ≥ 18 years, with ECOG PS 0-1. Cohort 1 will include patients with advanced radioactive-iodine refractory DTC who progressed to previous TKIs (including but not limited to lenvatinib, sunitinib or cabozantinib) and cohort 2 will include patients with advanced or metastatic ATC who may be on first-line or progressed to a previous systemic treatment. Patients will have not received previously chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that are not completed 2 weeks before first dose of study treatment (See Section 6 for further detail on eligibility). All enrolled patients will receive sacituzumab govitecan (10 mg/kg intravenously) on Days 1 and 8 of a 21-day cycle. Patients will be treated until progression, death, study withdrawal, or unacceptable toxicity. Sacituzumab govitecan is administered intravenously as a slow infusion as described below. Dosing is based on the patient's body weight on Day 1 of each cycle (or at each dosing day if change in body weight is \>10% or if required by institutional policy). Sacituzumab govitecan at 10 mg/kg will be the highest assigned dose. Dose reductions and delays will be allowed. All patients will undergo periodic tumor assessments by CT or MRI scan every 12 weeks ± 14 days (3 months), and blood monitoring of tumor markers (i.e. thyroglobulin if applicable) every 12 weeks ± 3 days (3 months) from the start of study treatment until progression or patient withdrawal.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Dose of 10 mg/kg intravenously
Hospital Universitari Vall d'Hebron
Barcelona, Spain
RECRUITINGComplexo Hospitalario Universitario de Ferrol
Ferrol, Spain
NOT_YET_RECRUITINGInstitut Catala d´Oncologia (ICO) -Hospitalet
Hospitalet de Llobregat (Barcelona), Spain
RECRUITINGHospital Clínico San Carlos
Madrid, Spain
RECRUITINGHospital Universitario la Paz
Madrid, Spain
RECRUITINGHospital Universitario Ramón y Cajal
Madrid, Spain
NOT_YET_RECRUITINGMD Anderson Cancer Center Madrid
Madrid, Spain
RECRUITINGHospital General Universitario Morales Meseguer
Murcia, Spain
RECRUITINGHospital Universitario Central de Asturias
Oviedo, Spain
RECRUITINGH.U. Marqués de Valdecilla
Santander, Spain
RECRUITING...and 1 more locations
Objective response rate (ORR)
percentage/proportion of patients with confirmed complete response (CR) or partial response (PR) as their overall best response throughout the study period. Objective responses will be assessed locally by the investigator according to RECIST, version 1.1
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
Disease control rate (DCR)
Percentage/proportion of patients with complete response (CR) or partial response (PR), according to ORR definition for the trial, or maintained stable disease (SD) as their overall best response, assessed by imaging follow-up (CT scan/MRI) and RECIST 1.1 criteria. Stable disease should be maintained for at least 4 months to be considered as a CBR event.
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
Duration of response (DoR)
Time from first confirmed response (CR or PR), according to ORR definition for the trial, to the date of the documented PD as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment.
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
Progression-free survival (PFS)
Time from first dosing date to the date of confirmed PD according to RECIST 1.1. Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment.
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
Overall survival (OS)
Time elapsed from the first dose of study treatment until death from any cause. We will assess the median OS, estimated by Kaplan-Meier. Patients alive and free of events at the date of the analysis will be censored at their last known contact. Survival will be assessed by recording patient status at each visit. Long term follow up to be performed at least every 6 months.
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
Safety profile
Percentage/proportion of patients that experience adverse events classified by their type, severity and seriousness according to the National Cancer Institute's Common Toxicity criteria (NCI-CTCAE v5.0) scoring system.
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
Patient self-reported quality of life (QoL)
Assessed at baseline and every 12 weeks until progression through the EORTC QLQ-C30 questionnaire. The questionnaire is a validated tool composed of 30 questions or items that assess QoL in relation to physical, emotional, social aspects. The questionnaire is structured in 5 functional scales (physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, only in items 29 and 30 are they evaluated with a score of 1 to 7 (1: dreadful, 7: excellent). The scores obtained are standardized to 0-100.
Time frame: Throughout the study period, approximately 42 months since the inclusion of first patient
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.