To characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of LXS196 as a single agent or LXS196 in combination with HDM201 in patients with metastatic uveal melanoma.
ID
Source
Brief title
Condition
- Ocular neoplasms
- Ocular neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To characterize the safety and tolerability of LXS196 alone or LXS196 in
combination with HDM201 and to identify the MTD and/or Recommended dose for
expansion (RDE).
Secondary outcome
To evaluate the preliminary antitumor activity of LXS196 alone or LXS196 in
combination with HDM201
To characterize the pharmacokinetic profile of LXS196 alone or LXS196 in
combination with HDM201
To assess the pharmacodynamic effect of LXS196 alone or LXS196 in combination
with HDM201
Background summary
LXS196 is a potent, orally bioavailable, selective inhibitor of the PKC family
of kinases. In pre-clinical uveal melanoma efficacy models, LXS196 dosed as a
singel agent leads to tumor regression. LXS196 therefore provides the
opportunity to treat uveal melanoma patients with a potent, PKC selective
therapy that targets one of the key downstream singanling pathwasy from the
GNAQ/GNA11 mutations that characterize this disease.
LXS196 have not been tested before in patients with uveal melanoma and it is
not known if it will be effective on the tumor or how effective it will be.
HDM201 is also a new investigational drug. HDM201 may restore the normal
function of a protein called p53, which usally does not function properly in
cancer, leading to uncontrolled tumor growth. Combining these two drugs
together may slow down the rate of tumor growth more than either drug alone.
Study objective
To characterize the safety, tolerability, pharmacokinetics (PK),
pharmacodynamics (PD), and preliminary anti-tumor activity of LXS196 as a
single agent or LXS196 in combination with HDM201 in patients with metastatic
uveal melanoma.
Study design
A phase 1, open-label, study consisting of a dose escalation part followed by a
dose expansion part in patients with metastatic uveal melanoma.
Intervention
Phase 1 with LXS196 and LXS196 in combination with HDM201.
Study burden and risks
Toxicities of the treatment with LXS196 alone or LXS196 in combination with
HDM201.
Tumorbiopsies.
Exposure to radiation, CTScan (MRI or PETscan). Frequent visits and blooddrawn.
See attachment of the ICF for the overview of the assesments during each visit.
And see also the attachment of the ICF for the side effects.
There is no quarentee that participation of this trial has direct benefit for
the patient. OBtained results could help developement in the future. The burden
on the patient is as expected in a phase 1 study.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
*Male or female patients *18 years of age, *Metastatic histologically or
cytologically confirmed uveal melanoma with pathologic confirmation that is
judged to be progressive in the opinion of the treating physician.,
*Willingness to provide newly obtained tumor tissue at baseline and on
treatment unless contraindicated by medical risk in the opinion of the treating
physician., *Measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded)
as > 20 mm with conventional techniques or as >10 mm with CT scan. ,
*ECOG performance status * 1, Other protocol-defined inclusion criteria may
apply.
Exclusion criteria
*Malignant disease other than that being treated in this study. Exceptions are
described in section 5.2., *Symptomatic or untreated leptomeningeal or brain
metastases or spinal cord compression. Treated brain metastases must have been
stable for at least 1 month., *Impaired cardiac function or clinically
significant cardiac diseases including history or presence of ventricular
tachyarrhythmias or any uncontrolled arrhythmia., *Patients who are receiving
treatment with medications that cannot be discontinued prior to study entry and
that are considered to be any of the following:, -known and possible risk for
QT prolongation, -known to be strong inducers or inhibitors of CYP3A4/5, -known
to be inducers or inhibitors of P-gp, -known to be substrates of CYP3A4/5 and
P-gp with a narrow therapeutic Index, *Patients with abnormal laboratory
values, defined as any of the following:, -AST or ALT > 3 times ULN, AST or
ALT > 5 times ULN for patients with liver metastases., -Total bilirubin >
1.5 x ULN, except for patients with Gilbert*s syndrome who are excluded if
total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN., -Absolute
neutrophil count (ANC) * 1.5 x 10e9/L (1500/mm3)., -Platelets * 100 x 10e9/L
(100,000/mm3)., -Hemoglobin (Hgb) * 90 g/L (9 g/dL)., Other protocol-defined
exclusion criteria may apply., Update AM3:
- Creatinine > 1.5x ULN
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 |
|---|---|
| EudraCT | EUCTR2015-002158-11-NL |
| CCMO | NL55535.058.15 |