A Phase 3 Trial Comparing LOXO-292 to Cabozantinib or Vandetanib in Patients with RET-Mutant Medullary Thyroid Cancer
- Conditions
- Male or female patients with progressive, advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid CancerMedDRA 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-FR
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
- 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 investigator
- A RET gene alteration in tumor, genomic DNA or blood.
- Adequate hematologic, hepatic and renal function
- Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months after
- 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 310
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
- Additional validated oncogenic driver in MTC if known
- Prior systemic treatment with kinase inhibitor(s)
- Major surgery (excluding placement of vascular access) within 4 weeks prior to planned start of study treatment
- Radiotherapy within 1 week of the first dose of study treatment (within 4 weeks if >30% bone marrow irradiated)
- 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
- Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
- Current treatment with proton pump inhibitors (PPIs)
- Known hypersensitivity to any of the excipients of LOXO-292 or cabozantinib
- Pregnancy or lactation
- Active second malignancy
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare TFFS of patients with progressive, advanced, kinase inhibitor naïve, RET-mutant MTC treated with LOXO-292 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 LOXO-292 versus cabozantinib or vandetanib<br><br>- To evaluate the safety and tolerability of LOXO-292 compared to cabozantinib or vandetanib<br><br>- To compare the tolerability of LOXO-292 versus cabozantinib or vandetanib<br>;Primary end point(s): Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)<br>TFFS by BICR<br>;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 Outcome Measures
Name Time Method Secondary end point(s): 1. Progression Free Survival (PFS) by BICR (PFS by BICR)<br>2. ORR: Percentage of Participants with Complete Response (CR) or Partial Response (PR) by BICR<br>3. Duration of Response (DoR) by BICR<br>4. Overall Survival (OS)<br>6. PFS2 by Investigator<br>7. Comparative Tolerability: Patient-Reported Outcomes (Functional Assessment of Cancer Therapy-Side Effects [FACT-GP5]);Timepoint(s) of evaluation of this end point: 1. Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months)<br>2. Baseline through Disease Progression or Death (Estimated at up to 30 Months)<br>3. Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months)<br>4. Baseline to Date of Death from Any Cause (Estimated at up to 60 Months)<br>5. Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 48 Months)<br>6. Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause (30 months)