A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing selpercatinib (LOXO-292) to Physicians Choice of Cabozantinib or Vandetanib in Patients with Progressive, Advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)
- Conditions
- Oncology - ThyroidMedullary Thyroid CancerThyroid cancer
- Registration Number
- NL-OMON49573
- Lead Sponsor
- Eli Lilly
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 8
1. Are of an acceptable age to provide informed consent according to local
regulations and
are at least 18 years of age (patients as young as 12 years of age will be
allowed if
permitted by local regulatory authorities and institutional review boards).
2. Histologically confirmed, unresectable, locally advanced and/or metastatic
MTC and no
prior history of treatment with kinase inhibitors for advanced/metastatic
disease. Prior
systemic or radiation therapy in the adjuvant setting may be allowed with
discussion and
approval by the Lilly CRS/CRP.
3. Radiographic progressive, measurable disease per RECIST 1.1 (Eisenhauer et
al. 2009) at
screening compared with a previous image taken within the prior 14 months as
assessed
by the BICR.
4. A RET gene alteration identified in a tumor, germline DNA or blood sample,
as defined
in Appendix 6 of the protocol. The RET alteration result should be generated
from a laboratory with
CLIA, ISO/EIC, CAP, or other similar certification. Lilly should be contacted
to discuss
test results from labs where such certification is not clearly demonstrated to
determine
eligibility. In all cases, a redacted Molecular Pathology Report or other
report(s)
describing tumor and/or germline RET (and other) alteration analysis should be
submitted to Lilly or designee during/prior to eligibility.
a. Mandatory provision of an unstained, archived tumor tissue sample in a
quantity
sufficient to allow for retrospective central analysis of RET mutation status
(for
confirmation). Please refer to Section 8.8.1 for details.
b. Participants must have adequate unstained, archived tumor tissue sample, as
defined in Section 8.8.1, for retrospective central confirmation of the RET
result.
5. Eastern Cooperative Oncology Group (ECOG) performance status score (Oken et
al.
1982) of 0 to 2.
6. Ability to swallow capsules and comply with treatment, laboratory
monitoring, and
required clinic visits for the duration of study participation
7. Patients must have discontinued from previous treatments as shown in the
protocol and fully
recovered. Consult with the Lilly CRS/CRP for the appropriate length of time
prior to
the first dose of study treatment on additional therapies not mentioned.
8. Have adequate organ function, as defined in the protocol.
9. Patients must have normal serum potassium, calcium, and magnesium levels
(may be
receiving supplements).
10. Men with partners of childbearing potential or women of childbearing
potential must
agree to use a highly effective contraceptive method (for example, intrauterine
device
[IUD], birth control pill, or barrier method) during treatment with study drug
and for
6 months following the last dose of study drug. If a condom is used as a barrier
contraceptive, a spermicidal agent should be added as double-barrier
protection. See
Appendix 3 of the protocol.
Note: Unless not allowed by local regulations, women of childbearing potential
who are
abstinent (if this is complete abstinence, as their preferred and usual
lifestyle) or in a
same-sex relationship (as part of their preferred and usual lifestyle) must
agree to either
remain abstinent or stay in a same-sex relationship without sexual
relationships with
males unless they agree to use contraceptive method known
13. An additional validated oncogenic driver in MTC if known that could cause
resistance to
LOXO-292 treatment. Examples include, but are not limited to RAS gene mutations
and
ALK gene fusions.
14. Symptomatic CNS metastases, leptomeningeal carcinomatosis, or untreated
spinal cord
compression. Patients are eligible if neurologically stable and without
increase in steroid
dose for 14 days prior to the first dose of study treatment and no CNS surgery
or
radiation has been performed for 28 days, 14 days if stereotactic radiosurgery
(SRS).
15. 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
on more
than one ECG during Screening. Correction of suspected drug-induced QTcF
prolongation may be attempted at the investigator*s discretion if clinically
safe to do so.
Patients who are intended to receive vandetanib if randomized to the control arm
ineligible if QTcF is >450msec.
a. Note: Patients with implanted pacemakers may enter study without
meeting QTc criteria due to nonevaluable measurement.
16. Active uncontrolled systemic bacterial, viral, or fungal infection or
serious ongoing
intercurrent illness, such as hypertension or diabetes, despite optimal
treatment, a clinical
diagnosis or symptoms of interstitial lung disease, or other serious medical
conditions which in the medical judgment of the investigator would prevent the
patient from safely
participating (screening for chronic conditions is not required).
17. Clinically significant active malabsorption syndrome or other condition
likely to affect
gastrointestinal absorption of the study drug.
18. Uncontrolled symptomatic hyperthyroidism or hypothyroidism
19. Uncontrolled symptomatic hypercalcemia or hypocalcemia
20. Active hemorrhage or at significant risk for hemorrhage.
21. Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the
cervix or
malignancy diagnosed >=2 years previously and not currently active. Patients
receiving
adjuvant hormone therapy for breast or prostate cancer with no evidence of
disease are eligible. Participants with MEN2-associated pheochromocytoma are
eligible if the pheochromocytoma is, in the opinion of the investigator,
documented to be stable or has been resected (and patient has fully recovered
from surgery).
22. Prior systemic treatment with kinase inhibitor(s)
23. Require concomitant use of strong CYP3A4 inhibitors or inducers (see
Appendix 7 of the protocol)
24. Require treatment with proton pump inhibitors (PPIs)
25. Are taking a concomitant medication that is known to cause QTc prolongation
(for
examples, see Appendix 7 of the protocol)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* TFFS by BICR</p><br>
- Secondary Outcome Measures
Name Time Method <p>* PFS by BICR<br /><br>* TFFS by investigator<br /><br>* TFFS by investigator<br /><br>* ORR by investigator and BICR<br /><br>* DoR by investigator and BICR<br /><br>* OS<br /><br>* PFS2 by investigator<br /><br><br /><br>* Safety per CTCAE v5.0 (including but not limited to): incidence and severity<br /><br>of TEAEs, SAEs, deaths, and clinical laboratory abnormalities.<br /><br><br /><br>* FACT-GP5<br /><br>* PRO CTCAE</p><br>