Oncology - Thyroid Medullary Thyroid Cancer
Conditions
Interventions
Arm A: Intervention Selpercatinib, twice daily Arm B1: Intervention
Cabozantinib, once daily Arm B2: Intervention Vandetanib, once daily Cycle
length is 28 days for all treatment arms.
Sponsors
Eli Lilly
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Age: All patients of 16 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 marrow irradiated). - Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 4 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 breastfeeding during treatment and for at least 4 months after the last dose of study drug. - Written informed consent
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 Criteria 2b). -Are taking a concomitant medication that is known to cause QTc prolongation. - Life expectancy =2 years previously and not currently active
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) by Blinded Independent Committee Review (BICR) - PFS by BICR | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Netherlands
Outcome results
None listed