This study has been transitioned to CTIS with ID 2023-506782-56-00 check the CTIS register for the current data. To compare PFS of patients with progressive, advanced, kinase inhibitor naïve, RET-mutant MTC treated with selpercatinib versus…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Oncology - Thyroid
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression Free Survival (PFS) by Blinded Independent Committee Review (BICR)
- PFS by BICR
Secondary outcome
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.
Background summary
Medullary thyroid cancer (MTC) accounts for 1% to 2% of thyroid cancers in the
United States, with approximately 1000 new cases per year (SEER 2018). The
majority of MTCs are sporadic, with approximately 20% to 25% hereditary due to
a germline activating mutation in the RET gene.
Patients with RET-mutant MTC comprise a population with high unmet need.
Chemotherapy is ineffective for MTC. Therefore, there is an urgent need to
identify new targeted therapies that potently inhibit RET-mutant MTC, while
sparing other kinase and nonkinase off-targets that contribute to significant
toxicity
Selpercatinib is a highly potent and specific inhibitor of the RET RTK, with
minimal inhibition of other kinase and non-kinase targets, and therefore may be
of benefit to patients with MTC that harbor RET alterations and/or depend on
RET activation. This Phase 3 study is required to confirm the benefit from
selpercatinib seen in patients with advanced/metastatic MTC in the LIBRETTO-001
trial and to better understand this benefit in the context of other available
treatments for advanced/metastatic MTC.
Study objective
This study has been transitioned to CTIS with ID 2023-506782-56-00 check the CTIS register for the current data.
To compare PFS of patients with progressive, advanced, kinase inhibitor naïve,
RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib.
Study design
This is a global, multicenter, randomized (2:1), open-label, Phase 3 study
comparing selpercatinib (treatment arm 1) to physicians choice of cabozantinib
or vandetanib (treatment arm 2) in patients with progressive, advanced, kinase
inhibitor naïve, RET-mutant Medullary Thyroid Cancer (LIBRETTO-531).
Intervention
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.
Study burden and risks
Benefit: Selpercatinib is a highly potent and specific inhibitor of the RET
RTK, with minimal inhibition of other kinase and non-kinase targets, and
therefore may be of benefit to patients with MTC that harbor RET alterations
and/or depend on RET activation. Given its manageable toxicity profile and
evidence of durable antitumor activity in patients with advanced RET mutant
MTC, Selpercatinib may be of benefit in delaying treatment failure and disease
progression.
Risk: The most common toxicities associated with Selpercatinib are monitorable
and reversible and include dry mouth, diarrhea, hypertension, fatigue,
constipation, AST/ALT elevation, headache, nausea, peripheral edema, and
increased blood creatinine.
Burden: Patients receiving the treatment would be advised to avoid grapefruit
juice, usage of certain medications. Additionally, patients treated with
Vandetanib would be advised to avoid sun exposure during the study and for up
to 4 months after the end of the study.
During the study patients will be exposed to the burden of increase monitoring
of vital signs, therefor more frequent hospital visits and invasive procedures,
such as: venapunction, biopsy and radiation procedures.
Due to the manageable toxicity profile of Selpercatinib and evidence of durable
antitumor activity in patients with advanced RET-mutant MTC, the expected
benefits of the researched treatment outweigh the potential risks.
Lilly Corporate Center, Delaware St 893
Indianapolis IN46285
US
Lilly Corporate Center, Delaware St 893
Indianapolis IN46285
US
Listed location countries
Age
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
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506782-56-00 |
| EudraCT | EUCTR 2019-001978-2-NL |
| ClinicalTrials.gov | NCT04211337 |
| CCMO | NL75905.031.20 |