A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
Purpose
The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.
Condition
- Medullary Thyroid Cancer
Eligibility
- Eligible Ages
- Over 12 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
- At least 18 years of age (participants as young as 12 years of age will be allowed
if permitted by local regulatory authorities).
- Histologically or cytologically confirmed, unresectable, locally advanced and/or
metastatic MTC and no prior history of treatment with kinase inhibitors for
advanced/metastatic disease.
- Radiographic progressive disease per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 at screening compared with a previous image taken within the prior 14
months as assessed by the BICR. Participants with measurable or non-measurable but
evaluable disease are eligible; however, participants with non-measurable disease
may not have disease limited to bone sites only.
- A defined/acceptable RET gene alteration identified in a tumor, germline
deoxyribonucleic acid (DNA) or blood sample.
- Tumor tissue in sufficient quantity to allow for retrospective central analysis
of RET mutation status
- Eastern Cooperative Oncology Group performance status score of 0 to 2.
- Adequate hematologic, hepatic, and renal function and electrolytes.
- Men and women of childbearing potential must agree to use a highly effective
contraceptive method during treatment with study drug and for 4 months following the
last dose of study drug.
- Ability to swallow capsules.
Exclusion Criteria:
- An additional validated oncogenic driver in MTC if known that could cause resistance
to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF
gene mutations and NTRK gene fusions.
- Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis,
or untreated spinal cord compression.
- Clinically significant active cardiovascular disease or history of myocardial
infarction within 6 months, history of Torsades de pointes, or prolongation of the
QTcF >470 milliseconds on more than one electrocardiogram (ECG) during screening.
Participants who are intended to receive vandetanib if randomized to the control arm
are ineligible if QTcF is >450 milliseconds.
- Active uncontrolled systemic bacterial, viral, or fungal infection or serious
ongoing uncontrolled intercurrent illness.
- Active hemorrhage or at significant risk for hemorrhage.
- Other malignancy unless nonmelanoma skin cancer, carcinoma in situ or malignancy
diagnosed ≥2 years previously and not currently active. Participants with multiple
endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Selpercatinib - Treatment A (TRT A) |
160 milligrams Selpercatinib administered orally (PO) twice daily (BID). Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID). |
|
|
Active Comparator Cabozantinib or Vandetanib - Treatment B (TRT B) |
140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice. Cabozantinib Adolescent Dose: 40 mg/m2. Vandetanib Adolescent Dose: - 0.7 - <0.9 - 100 mg every other day (QOD) - 0.9 - <1.2 - 100 mg QD - 1.2 - <1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - ≥1.6 - 200 QD |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Loxo Oncology, Inc.
Study Contact
Detailed Description
Adaptive sample size re-estimation will be performed at interim analysis. The sample size could be increased from approximately 250 to 400 depending on the results of interim analysis.