E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male or female patients with progressive, advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027105 |
E.1.2 | Term | Medullary thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare PFS of patients with progressive, advanced, kinase inhibitor naïve, RET-mutant MTC treated with selpercatonib versus cabozantinib or vandetanib. |
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E.2.2 | Secondary objectives of the trial |
- 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
- To evaluate the safety and tolerability of LOXO-292 compared to cabozantinib or vandetanib
- To compare the tolerability of LOXO-292 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 patients receiving selpercatinib. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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.
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E.4 | Principal 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 LOXO-292 or cabozantinib - Pregnancy or breastfeeding - Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or malignancy diagnosed =2 years previousl and not currently active |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) by Blinded Independent Committee Review (BICR) PFS by BICR
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E.5.1.1 | 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) |
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E.5.2 | 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. |
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E.5.2.1 | 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) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Canada |
China |
Czechia |
France |
Germany |
Greece |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 11 |