A Phase 1 Dose Escalation Study of ARQ 197 Administered in Combination With Gemcitabine in Adult Patients With Advanced Solid Tumors
Enrollment of an initial cohort of 3 or 6 patients will follow the traditional "3 + 3" dose
escalation scheme. These patients will be treated with ARQ 197 and gemcitabine. ARQ 197 will
be administered by mouth BID continuously. Gemcitabine will be administered by intravenous
infusion over 30 minutes once weekly for 3 consecutive weeks followed by a week of rest. The
dosing schedules of ARQ 197 and gemcitabine will be as described below.
ARQ 197 will be administered per the following cohorts, starting from week 1 of treatment.
Cohort------ARQ 197 (mg BID)
A-----------120 (repeated treatments of 2 weeks followed by a 1 week pause)
B-----------240 (repeated treatments of 2 weeks followed by a 1 week pause)
C-----------360 (repeated treatments of 2 weeks followed by a 1 week pause)
D-----------360 (repeated treatments of 3 weeks followed by a 1 week pause)
In case of DLT, intermediate dosing cohorts will be explored, administering ARQ 197 for 5
days instead of 7 during the weeks of ARQ 197 administration.
For cohorts 0 and 1, gemcitabine is administered at the dose of 1000mg/sqm from week 1 of
treatment, 4 weeks in a row for the first month, then for 3 consecutive weeks followed by a
week of pause. For all other cohorts, gemcitabine will be administered starting from week 2
of treatment at the dose of 1000mg/sqm, for 3 consecutive weeks followed by a week of pause.
Additional treatment cohorts may be enrolled to explore intermediate, higher or lower doses
of ARQ 197, as indicated by the tolerability, safety profile, and pharmacokinetic (PK)
Once a safe and recommended dose level is determined, an Expanded Cohort of up to 60
patients with non-resectable cholangiocarcinoma (10 patients), breast carcinoma (10
patients), ovarian carcinoma (10 patients), endometrial carcinoma and carcinoma of the
cervix (10 patients in total, at least five with endometrial carcinoma). Each group of 10
patients may enroll up to three patients who received at least 5-week gemcitabine treatment.
The cohort will also include up to 20 patients with pancreatic carcinoma (up to five out of
20 patients may have received at least 5-week gemcitabine treatment).
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of ARQ 197 when administered in combination with gemcitabine.
Patients will remain on study until unacceptable toxicity, disease progression (clinical or radiological) or another discontinuation criterion is met.
United States: Food and Drug Administration
|Albany, Georgia 31701|
|Nashville, Tennessee 37203-1632|
|Austin, Texas 78705|