A Phase 2 Multi-Center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients with Advanced Fibrolamellar Carcinoma (FLC)
- Zale Lipshy University Hospital
Muhammad Beg, M.D.
This is a Phase 2 study in 29 patients with advanced FLC. Primary efficacy analysis will be based on overall response rate using ReCiST v 1.1 criteria. Secondary endpoints will include 6-month progression free survival rate, median PFS, TTP, and oS and the evaluation of safety.
Patients will be given an oral, daily dose of enMD-2076 based on body surface area. in case of adverse events, two dose reductions at the discretion of the investigator will be allowed for each patient. if adverse events resolve, the dose can be increased in 50 mg increments as tolerated. Dosing interruptions/delays will be allowed at the discretion of the investigator for recovery from adverse events or inter-current illness, particularly if the
patient is benefiting from therapy with enMD-2076. after a treatment interruption for adverse events, treatment can be resumed at a lower dose and increased in 50 mg increments as tolerated.
Tumor measurements will occur every two months ((+-) 1 week) after initial study drug administration. The investigator will make decisions on treatment effect during the study. The overall response rate will be determined based on ReCiST v 1.1 criteria. Survival and time to progression will be determined as the time from first study drug administration until death from any cause or documented progression. Patients who discontinue therapy for any reason other than progression will continue to receive imaging until progression or death.
an interim analysis will be conducted after 16 patients have completed overall response rate evaluation. The purpose of the interim analysis is to determine whether it is futile to continue the study and to check the assumptions regarding the required sample size.
*at this site no children will be enrolled on the study.
1. Histologically or cytologically confirmed advanced not amenable to curative resection fibrolamellar
a) This review will be conducted by a pathologist at the participating site to confirm the diagnosis. If there
is a discrepancy, a review of a different archived specimen if available (heterogeneity is common)
and/or identify a liver pathologist at another site who can provide independent review.
b) Archived specimens will be collected for subsequent immunohistochemistry, genomic analysis and
possibly other research.
2. All forms of prior local therapy are allowed as long as patients have either a target lesion, which has not
been treated with local therapy and/or the target lesion(s) within the field of the local-regional therapy that
has shown an increase of >= 20% in size. Local-regional therapy must be completed at least 4 weeks prior to
the baseline CT scan.
3. Patients with prior systemic regimens are allowed. There is no limitation to the number of previous
systemic regimens but must have recovered from any toxicity attributable to prioir therapy.
4. Are at least 4 weeks from major surgery or systemic therapy and recovered.
5. At least one measureable lesion by RECIST 1.1.
6. Male or non-pregnant, non-breastfeeding female at least 18 years of age. Patients aged at 12~18 years may
be recruited but only at the site principle investigator's request and subject to IRB approval.
7. Have clinically acceptable laboratory screening results within certain limits specified below:
* AST and ALT <= 5 times upper limit of normal (ULN)
* Total bilirubin <= 3.0 x ULN
* Creatinine <= 1.5 x ULN or Cr Cl > 60 cc/min
* Absolute neutrophil count >= 1500 cells/mm3
* Platelets >= 50,000/mm3
8. Have an ECOG performance status of 0-2 for >= 16 years of age and a Lansky performance status of 70-100
for < 16 years of age.
9. Women and men of child producing potential must agree to use effective contraceptive methods prior to
study entry, during study participation, and for at least 30 days after the last administration of study
medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for
women of childbearing potential.
10. Have the ability to understand the requirements of the study, provide written informed consent or assent,
which includes authorization for release of protected health information, abide by the study restrictions, and
agree to return for the required assessments.