Advanced/Recurrent Non-small-cell Lung Cancer
Conditions
Brief summary
This is a phase I study to determine the safety, tolerability and recommended phase II dose of ARQ 197 given in combination with erlotinib as primary endpoints in CYP2C19 poor metabolizer patients with advanced/recurrent non-small-cell lung cancer. The pharmacokinetic profile and antitumor activity of ARQ 197 administered alone or in combination with erlotinib will also be determined as secondary endpoints.
Interventions
Orally twice daily administration of ARQ197 and orally once daily administration of erlotinib hydrochloride
Sponsors
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntary written informed consent for study participation must be obtained * A histologically or cytologically confirmed advanced/recurrent non-small-cell lung cancer * History of ≥1 prior chemotherapy regimen (treatment with EGFR tyrosine kinase inhibitors will be counted as one regimen) * ECOG PS of 0 or 1 * Life expectancy of ≥3 months * Poor metabolizers as defined by CYP2C19 genotype
Exclusion criteria
* Anti-cancer chemotherapy, anti-cancer therapy with EGFR-TKI, hormone therapy, radiotherapy, immunotherapy, other investigational agents or anti-cancer antibody therapy within 28 days prior to ARQ 197 dose * Surgery for cancer within 28 days prior to ARQ 197 dose * Active double cancer * Known symptomatic brain metastases * An intercurrent illness that is uncontrolled (e.g., infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic arrhythmia, interstitial pneumonia) * Pregnant or lactating * Subjects who wish to have a child and who would not agree to use contraceptive measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity in the combination of tivantinib and erlotinib | DLT observation period started from the day of first single agent treatment to the day after the continuous combination treatment for 29 days. | Tivantinib was treated once as a single agent on Day 1. After 2 days of interruption, dayly treatments of the combination started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile of ARQ 197 | Plasma sample correction at pre-dose, 1, 2, 4, 6, 10, 12 and 24 hours on Day 1, and in addition, at pre-dose, 1, 2, 4, 6, 10, 12 hours on the day of the first comnibation treatment | Summary statistics of plasma concentration and pharmacokinetic parameters |
| Pharmacokinetic profile of Erlotinib | At pre-dose, 1, 2, 4, 6, 10, 12 hours on the day of the first comnibation treatment | Summary statistics of plasma concentration and pharmacokinetic parameters |
| Antitumor activity | Baseline, and then every 6 week of imaging until discontinuation criteria met | Response rate |
Countries
Japan
Outcome results
None listed