Esophagogastric Adenocarcinoma
Conditions
Brief summary
This is a single-arm phase I/Ib study of crenolanib combined with ramucirumab/paclitaxel as second line therapy for patients with advanced/metastatic adenocarcinoma of the esophagus, GEJ or stomach. Patients will be enrolled in two phases; dose escalation phase and dose expansion phase.
Interventions
DRUGCrenolanib
Crenolanib continuously on Days 1-28 at 1 of 3 BID doses - 60 mg, 80 mg or 100 mg
DRUGRamucirumab
Ramucirumab IV 8 mg/kg on Days 1 and 15 q28 days
DRUGPaclitaxel
Paclitaxel IV 80 mg/m2 on Days 1, 8 and 15 q28 days
Sponsors
Arog Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed adenocarcinoma of the esophagus, GEJ or stomach. * Stage IV disease or locally advanced/unresectable tumors * Prior progression on only 1 line of chemotherapy in the advanced/metastatic setting containing a fluoropyrimidine and/or platinum compound * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Exclusion criteria
* Prior treatment with a taxane is not permitted in the dose-expansion phase. Patients in the dose escalation component may have received a taxane in the peri-operative setting, provided they developed disease recurrence \>6 months after the completion of this therapy * Known pre-existing liver disease (e.g. cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, sclerosing cholangitis) * Patients with any clinically apparent ascites or who have undergone a paracentesis within 7 days of enrollment * Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg on repeated measurement) despite optimal medical management * Active or clinically significant cardiac disease * Patients with arterial thrombotic events, such as cerebrovascular accident or myocardial infarction, within 6 months of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD of oral continuous dosing of crenolanib (3 different doses) plus ramucirumab/paclitaxel in patients defined as the highest dose level in which <2 of 6 patients develop a DLT. The DLT is based on the 1st cycle adverse events. | 5 weeks | The DLT is based on the first cycle (35 days) adverse events. If at least 2 of 3 or 2 of up to 6 patients experience a DLT at the starting dose level, then the study will be paused and the starting dose will be re-assessed. The MTD is defined as the highest dose level in which \<2 of 6 patients develop a DLT. This will constitute the first part of the study which will enroll a maximum of 18 patients. |
| Response rate (RR) of the combination in patients will be radiographically evaluated until progressive disease (PD), intolerable toxicity, withdrawal of consent, physician's decision, death or the completion of 6 cycles. adenocarcinoma patients | Bi-monthly for up to 6 months. | — |
Countries
United States
Outcome results
None listed