A Phase 3 Trial Comparing Selpercatinib to Cabozantinib or Vandetanib in Patients with RET-Mutant Medullary Thyroid Cancer

Phase 1

• Conditions: Male or female patients with progressive, advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer; MedDRA version: 21.1Level: PTClassification code 10027105Term: Medullary thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001978-28-NL
• Lead Sponsor: Eli Lilly and Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-16
• Last Update Posted: 3 October 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 130

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 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
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

- 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 = 3 months.
- Current treatment with proton pump inhibitors (PPIs)
- Known hypersensitivity to any of the excipients of vandetanib or
cabozantinib
- Pregnancy or breastfeeding
- Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or malignancy diagnosed =2 years previously and not currently active

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified