Male or female patients with progressive, advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer MedDRA version: 21.1 Level: PT Classification code 10027105 Term: Medullary thyroid cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Retsevmo
Product Name: SELPERCATINIB
Product Code: LY3527723
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Selpercatinib
Current Sponsor code: LOXO-292
Concentration unit: mg mi
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age: All patients of 12 years of age and older, after giving assent / Legally designated representative/ participant written consent. Histologically confirmed, metastatic MTC - Radiographic progressive, measurable disease per BIRC at screening compared with a previous image taken within the prior 14 months as assessed by the BICR. Patients with measurable or non-measurable but evaluable disease are eligible; however, patients with non-measurable disease may not have disease limited to bone sites only. - A RET gene alteration in tumor, genomic DNA or blood. - Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. - Adequate hematologic, hepatic and renal function. - Patients must have serum potassium, calcium and magnesium levels above the lower limit of normal (may be receiving supplements) and not clinically significantly above the upper limit of normal. - Major surgery (excluding biopsy and placement of vascular access) within 4 weeks prior to planned start of study treatment. - Radiotherapy within 2 weeks of the first dose of study treatment (within 4 weeks if >25% bone narrow irradiated). - Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 6 months after the last dose of study drug. - Women of childbearing potential must: • have a negative pregnancy test (serum or urine, consistent with local regulations) documented within 24 hours prior to treatment with study drug. • not be breast-feeding during treatment and for at least 4 months after the last dose of study drug. - Written informed consent Are the trial subjects under 18? yes Number of subjects for this age range: 10 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 155 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Additional validated oncogenic driver in MTC if known - Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. - Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of study treatment or prolongation of the QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 470 msec - Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. Screening for chronic conditions is not required - Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug - Uncontrolled symptomatic hyperthyroidism or hypothyroidism. - Uncontrolled symptomatic hypercalcemia or hypocalcaemia. - Active haemorrhage or at significant risk for haemorrhage. - Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. - Prior systemic treatment with kinase inhibitor(s) (Refer to Section 5.1, Inclusion Criterion 2b). - Are taking a concomitant medication that is known to cause QTc prolongation. - Life expectancy =3 months. - Known hypersensitivity to any of the excipients of vandetanib or cabozantinib - Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or malignancy diagnosed =2 years previously and not currently active
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare PFS of patients with progressive, advanced, kinase inhibitor naïve, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib.;Secondary Objective: - To compare other efficacy outcomes, based on RECIST 1.1 criteria, observed in patients with progressive, advanced, kinase inhibitor naïve, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib - To evaluate the safety and tolerability of selpercatinib compared to cabozantinib or vandetanib - To compare the tolerability of selpercatinib versus cabozantinib or vandetanib - To assess/evaluate performance of local RET laboratory tests compared to a single, entral test. - To assess the PK of selpercatinib in patient receiving selpercatinib.;Primary end point(s): Progression Free Survival (PFS) by Blinded Independent Committee Review (BICR) PFS by BICR ;Timepoint(s) of evaluation of this end point: Time Frame: Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (Estimated at up to 30 Months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Treatment Failure Free Survival (TFFS) by BICR (TFFS by BICR) 2. TFFS by Investigator 3. PFS by Investigator 4. ORR: Percentage of Participants with Complete Response (CR) or Partial Response (PR) by BICR 5. Duration of Response (DoR) by BICR 6. Overall Survival (OS) 7. PFS2 by Investigator 8. Safety per CTCAE v5.0 (including but not limited to): incidence and severity of TEAEs, SAEs, deaths, and clinical laboratory abnormalities. 9. Proportion of time with high-side-effect bother based on FACT-GP5 10. RET mutation status 11. Predose plasma concentrations at Day 8 of Cycle 1, and at Day 1 of Cycles 2 through 6.;Timepoint(s) of evaluation of this end point: 1. Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months) 2. Baseline through Disease Progression or Death (Estimated at up to 30 Months) 3. Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months) 4. Baseline to Date of Death from Any Cause (Estimated at up to 60 Months) 5. Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 48 Months) 6. Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (30 months) | — |
Countries
Australia, Belgium, Brazil, Canada, China, Czechia, Czech Republic, France, Germany, Greece, India, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed