Phase I partPrimary:* Determine the maximum tolerated dose (MTD) or the recommended phase II dose (RP2D).Secondary:* Safety and tolerability, * ORR, duration of response (DOR), disease control rate (DCR), progression free survival (PFS) and time to…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase I: MTD or RP2D
Phase II: ORR.
Secondary outcome
Phase I:
Adverse events, ORR, DOR, DCR, PFS, TTR and PK characteristics of EGF816 and
metabolite LMI258. Determination of EGFR pathway induction.
Phase II:
Adverse events, ORR, DOR, DCR, PFS, TTR and OS PK characteristics of EGF816 and
metabolite LMI258.
Background summary
Based on preclinical data for EGF816 and the known clinical activity of other
3rd-generation epidermal growth factor receptor (EGFR) inhibitors, it is
expected that EGF816 would exhibit to significant antitumor activity in
non-small cell lung cancer (NSCLC) patients harboring the activating EGFR
mutations (e.g., L858R and ex19del) and/or the acquired/resistant *gatekeeper*
T790M mutation while sparing wild-type (WT) EGFR.
In the Phase I part (dose-escalation) of this study the maximum tolerated dose
(MTD) or recommended phase II dose (RP2D) has been determined and the
preliminary antitumor activity has been determined of single-agent EGF816 in
adult patients with stage IIIB/IV NSCLC harboring a documented EGFR T790M
mutation. The Phase I part will be conducted in NL with 2 centers, the EMC and
the AvL.
NL will participate in the Phase II part of the study with 3 centers: EMC, AVL
en MUMC. The purpose of the Phase II part is to evaluate the efficacy and
safety of single-agent EGF816 in the MTD/RP2D dose determined in Phase I in
adult patients with stage IIIB/IV NSCLC whose tumors harbor specific EGFR
mutations. The expansion and the phase II part will consist of 1 group (The
patients must not have received any prior systemic antineoplastic therapy in
the advanced setting (NSCLC stage IIIB or IV). However, patients who have
failed no more than 1 cycle of systemic
antineoplastic therapy in the advanced setting are allowed. Note: Neo-adjuvant
and adjuvant systemic therapies will be counted as 1 prior line of treatment if
relapse occurred within 12 months from the end of the neo-adjuvant/adjuvant
systemic therapy.
Study objective
Phase I part
Primary:
* Determine the maximum tolerated dose (MTD) or the recommended phase II dose
(RP2D).
Secondary:
* Safety and tolerability,
* ORR, duration of response (DOR), disease control rate (DCR), progression free
survival (PFS) and time to response (TTR), pharmacokinetics (PK) properties of
EGF816 and metabolite LMI258. Determination of EGFR pathway induction.
Phase II part
Primary:
* To evaluate the antitumor activity of EGF816 as measured by overall response
rate (ORR) determined by Blinded Independent Review Committee.
Secondary:
* Safety and tolerability, ORR, duration of response (DOR), disease control
rate (DCR), progression free survival (PFS) and time to response (TTR), overall
survival (OS), pharmacokinetics (PK) properties of EGF816 and metabolite
LMI258.
Study design
Multicenter phase I/II open-label dose-escalaton (phase I) and dose-expansion
(phase II) study.
Study treatment: EGF816 capsules or tablets once daily. Continuous dosing.
Cycles of 4 weeks.
Treatment until disease progression or unacceptable side effects. Patients who
discontinue study treatment for any reason other than disease progression will
be followed up for progression of disease and all patients will be followed for
survival.
Approx. 40 subjects for Phase II part and at least 180 for the phase I part.
Total at least 220.
NL will participate in the phase II part.
Intervention
Treatment with EGF816.
Study burden and risks
Risk: Adverse effects of EGF816.
Phase I
Burden: Cycles of 4 weeks. Cycle 1: 6 visits, Cycle 2: 5 visits, from cycle 3
onwards: 2 visits. Duration mostly 2 hours. 2-3 visits up to 8 hours.
Physical examination: 4x during cycle 1 en 2, 1x/cycle.
Blood tests (10-15 ml/occasion): cycle 1 and 2: 4x. Afterwards 2x per cycle.
Extra for biomarkers (20-30 ml/occasion): every 2nd cycle. Extra for PK
(2ml/sample): 3 days with 8 samples in 8 h and 6 days with 1 sample.
Pregnancy test: 3-5 times.
HCV en HBV tests: at least 1x
Tumor measurements: every 8 weeks.
ECG: during 5 days (there off 2 days with 2 ECGs in 2 h). In some centers
extended ECG monitoring: 2 days with 5 ECGs in 8 h (= PK days; instead of 2
ECGs in 2 h), 1 day with 2 ECGs in 2 h. 3 days with 1 ECG.
Tumorbiopsie: 1-2 obligated in phase I. 2x optional.
Phase II
Burden: Cycles of 4 weeks. Cycle 1: 5 visits, Cycle 2: 3 visits from cycle 3
onwards: 2 visits. Duration mostly 2 hours. 2-3 visits up to 8 hours.
Physical examination: once/cycle.
Blood tests (10-15 ml/occasion): once per cycle. Extra for biomarkers (20-30
ml/occasion): every third cycle. Extra for PK (2ml/sample): 3 days with 8
samples in 8 h and 6 days with 1 sample.
Pregnancy test: 3-5 times.
HCV en HBV tests: at least 1x
Tumor measurements: every 8 weeks.
ECG: during 8 days, 2 days with 5 ECGs in 8 h, 1 day with 2 ECGs in 2 h and 5
days with 1 ECG.
Tumorbiopsie: 1-2 times optional.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
• Female and male patients >= 18 years of age.
• Stage IIIB/IV EGFR mutant NSCLC, histologically or cytologically confirmed.
• Patients with controlled brain metastases may participate in the trial. See
protocol page 14 for details.
• Measurable disease.
• ECOG performance status 0, 1.
• HBV under control and HCV negative., Specific criteria groups 1-6 (see also
protocol page 14-15) for phase I and II:
Group 1:
• EGFR activating mutation (e.g., L858R and/or ex19del)
• no systemic antineoplastic therapy for advanced NSCLC (no more than 1 cycle
of chemotherapy in the advanced setting is allowed)
Group 2:
• EGFR activating mutation (e.g., L858R and/or ex19del) and
• acquired EGFR T790M mutation
• progressed on 1 and only 1 prior treatment with a 1st-generation EGFR TKI or
2nd-generation EGFR TKI
• no more than 3 prior lines of systemic antineoplastic therapies in the
advanced setting
• EGFR TKI treatment must be the last prior treatment before study entry
Group 3:
• *de novo* EGFR T790M mutation (see protocol page 14-15)
• no more than 3 prior lines of systemic antineoplastic therapies in the
advanced setting
• no prior treatment with any therapy known to inhibit EGFR
Group 4:
• EGFR exon 20 insertion or deletion
• no more than 3 prior lines of systemic antineoplastic therapies in the
advanced setting
Group 5:
• EGFR activating mutation (e.g., L858R and/or ex19del) and
• without an acquired EGFR T790M mutation
• progressed on 1 and only 1 prior treatment with a 1st-generation EGFR TKI or
2nd-generation EGFR TKI
• no more than 3 prior lines of systemic antineoplastic therapiesin the
advanced setting
• EGFR TKI treatment must be the last prior treatment before study entry
Group 6:
• EGFR activating mutations (e.g., L858R or ex19del) and
• an acquired T790M mutation
• had treatment with a 1st/2ndgeneration EGFR TKI
• progressed on or are intolerant to a 3rd-generation EGFR TKI
• no more than 3 prior lines of systemic antineoplastic therapies in the
advanced setting
• 3rd-generation EGFR TKI treatment must be the last prior treatment before
study entry
Exclusion criteria
• Interstitial pneumonitis or interstitial lung disease.
• History of malignicity last 3 year
• Strong inhibitors or inducers of CYP3A4/5 that cannot be discontinued 1 week
prior to the start of EGF816.
• Pregnancy, lactation, inadequate contraception (males and females).
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 |
|---|---|
| Other | clinicaltrilas.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2013-004482-14-NL |
| CCMO | NL54070.031.15 |