Sacituzumab govitEcan in THYroid Cancers

Last updated: October 31, 2024
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Sacituzumab govitecan

Clinical Study ID

NCT06235216
GETNE T2318
2023-504898-20
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved writteninformed consent.

  2. Patient is ≥ 18 years of age.

  3. Patient has histologically confirmed metastatic or locally advanced unresectableradioactive-iodine refractory differentiated thyroid cancer (cohort A) or anaplasticthyroid carcinoma (cohort B).

  4. Prior therapy in each cohort:

  5. Cohort A: Patients must have experienced progression on at least one previoustreatment line with approved systemic therapies (Sorafenib, Lenvatinib orCabozantinib) and a maximum of 3 prior systemic therapies.

  6. Cohort B: Patients should be included in first-line setting or after failure ofany systemic therapy (up to 1 prior treatment lines).

  7. Patient has radiographically documented and measurable metastatic or locallyadvanced disease at baseline.

  8. An archival tumor tissue sample should be available for submission to the centrallaboratory for translational studies. If an archival tumor tissue sample is notavailable, a new biopsy tissue sample should be provided. No central pathologicalreview will be needed to include the patient in the trial.

  9. Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  10. The following baseline laboratory data without transfusional support:

  11. Neutrophil count (ANC) ≥ 1,500/mm3.

  12. Platelet count ≥ 100 × 109/L.

  13. Hemoglobin ≥ 9 g/dL.

  14. Serum bilirubin ≤ 1.5 × upper limit of normal (ULN). Note: patients withGilbert's disease are excluded.

  15. Serum albumin > 3 g/dL.

  16. Creatinine clearance (CrCl) ≥ 60 mL/min as estimated by the Cockroft-Gaultformula or as measured by 24 hour urine collection (GFR can also be usedinstead of CrCl).

  17. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULNor ≤ 5 xULN for patients with liver metastases.

  18. Female patients must either:

  19. Be of nonchildbearing potential:I)Postmenopausal *(defined as at least 1 year without any menses) prior toscreening , or II) Documented surgically sterile (e.g.hysterectomy, bilateralsalpingectomy, bilateral oophorectomy, or bilateral tubal occlusion). *Those who are amenorrheic due to an alternative medical cause are notconsidered postmenopausal and must follow the criteria for childbearingpotential subjects.OR

  20. If of childbearing potential: I) Agree not to try to become pregnant during the study and for at least 6 monthsafter the final study drug administration, II) And have a negative urine or serumpregnancy test within 7 days prior to Day 1 (females with false positive results anddocumented verification of negative pregnancy status are eligible forparticipation), III) And if heterosexually active, agree to abstinence (if in linewith the usual preferred lifestyle of the patient) or consistently use a condom plus 1 form of highly effective birth control per locally accepted standards starting atscreening and throughout the study period and for at least 6 months after the finalstudy drug administration.

  21. Female patients must agree not to breastfeed or donate ovules starting at screeningand throughout the study period, and for at least 6 months after the final studydrug administration.

  22. Male patients must not donate sperm starting at screening and throughout the studyperiod, and for at least 6 months after the final study drug administration.

  23. Male patients with a partner with childbearing potential, or who is pregnant orbreastfeeding must agree to abstinence or use a condom plus 1 form of highlyeffective birth control throughout the study period and for at least 6 months afterthe final study drug administration.

  24. Patient agrees not to participate in another interventional study while on treatmentin the present study.

Exclusion

Exclusion Criteria:

  1. Patient has central nervous system (CNS) metastases.

  2. Patient has ongoing clinically significant toxicity (Grade 2 or higher with theexception of alopecia) associated with prior treatment (including systemic therapy,radiotherapy or surgery). Note: if patients received major surgery, they must have recovered adequately fromthe toxicity and/or complications from the intervention prior to starting therapy.

  3. Patient has a history of another malignancy within 3 years before the first dose ofstudy drug, or any evidence of residual disease from a previously diagnosedmalignancy. Note: Patients with non melanoma skin cancer, curatively treated localized prostatecancer, or carcinoma in situ of any type (if complete resection was performed) areallowed.

  4. Patient has known active Hepatitis B or active hepatitis C:

  5. Patients who test positive for hepatitis B surface antigen (HBsAg). Patientswho test positive for hepatitis B core antibody (anti-HBc) will require HBV DNAby quantitative polymerase chain reaction (PCR) for confirmation of activedisease.

  6. Patients who test positive for HCV antibody. Patients who test positive for HCVantibody will require HCV RNA by quantitative PCR for confirmation of activedisease. Patients with a known history of HCV or a positive HCV antibody testwill not require a HCV antibody at screening and will only require HCV RNA byquantitative PCR for confirmation of active disease.

  7. Patients who test positive for HIV antibody.

  8. Patient has a known history of human immunodeficiency virus (HIV) infection (HIV 1or 2) with detectable viral load OR taking medications that may interfere with SN-38metabolism.

  9. Patient has documented history of a cerebral vascular event (stroke or transientischemic attack), or the following criteria for cardiac disease:

  10. Myocardial infarction or unstable angina pectoris within 6 months ofenrollment.

  11. History of serious ventricular arrhythmia (ie, ventricular tachycardia orventricular fibrillation), high-grade atrioventricular block, or other cardiacarrhythmias requiring antiarrhythmic medications (except for atrialfibrillation that is well controlled with antiarrhythmic medication); historyof QT interval prolongation.

  12. New York Heart Association (NYHA) class III or greater congestive heart failureor left ventricular ejection fraction of < 40%.

  13. Known history of clinically significant active COPD, or other moderate-to-severechronic respiratory illness present within 6 months prior to the first dose of studydrug.

  14. Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohndisease) and patients with a history of gastrointestinal obstruction or perforationwithin 6 months of enrollment.

  15. Patient has uncontrolled hypertension or diabetes.

  16. Patient has radiotherapy or major surgery within 4 weeks prior to the first dose ofstudy drug.

  17. Patients has received a live vaccine within 30 days, or antibiotics within one weekprior to the first dose of study drug.

  18. Patient has had chemotherapy, biologics, investigational agents, and/or antitumortreatment with immunotherapy that is not completed 2 weeks prior to the first doseof study drug. Note: Patients participating in observational studies are eligible.

  19. Patient has previously received topoisomerase 1 inhibitors.

  20. Patient has known hypersensitivity to sacituzumab govitecan or to any excipientcontained in the drug formulation.

  21. Patient has other underlying medical conditions that, in the opinion of theinvestigator, would impair the ability of the patient to receive or tolerate theplanned treatment and follow-up.

Study Design

Total Participants: 42
Treatment Group(s): 1
Primary Treatment: Sacituzumab govitecan
Phase: 2
Study Start date:
September 13, 2024
Estimated Completion Date:
December 31, 2027

Study Description

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.

Connect with a study center

  • Hospital Universitari Vall d&#39;Hebron

    Barcelona,
    Spain

    Active - Recruiting

  • Hospital Universitari Vall d'Hebron

    Barcelona,
    Spain

    Site Not Available

  • Complexo Hospitalario Universitario de Ferrol

    Ferrol,
    Spain

    Site Not Available

  • Institut Catala d´Oncologia (ICO) -Hospitalet

    Hospitalet de Llobregat (Barcelona),
    Spain

    Active - Recruiting

  • Hospital Clínico San Carlos

    Madrid,
    Spain

    Active - Recruiting

  • Hospital Universitario Ramón y Cajal

    Madrid,
    Spain

    Site Not Available

  • Hospital Universitario la Paz

    Madrid,
    Spain

    Active - Recruiting

  • MD Anderson Cancer Center Madrid

    Madrid,
    Spain

    Active - Recruiting

  • Hospital General Universitario Morales Meseguer

    Murcia,
    Spain

    Active - Recruiting

  • Hospital Universitario Central de Asturias

    Oviedo,
    Spain

    Active - Recruiting

  • H.U. Marqués de Valdecilla

    Santander,
    Spain

    Active - Recruiting

  • Hospital Universitario Miguel Servet

    Zaragoza,
    Spain

    Active - Recruiting

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