Clinical trial NCT03193918: Study of Crenolanib With Ramucirumab and Paclitaxel for Advanced Esophagogastric Adenocarcinoma
Official title: Phase I/Ib Study of Crenolanib With Ramucirumab and Paclitaxel as Second Line Therapy for Advanced Esophagogastric Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Esophagogastric Adenocarcinoma
Lead sponsor: Arog Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-06-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 5 weeks
measure: 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
timeFrame: Bi-monthly for up to 6 months.
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Geoffrey Ku, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moy RH, Greally M, Chou JF, Li J, Desai AM, Chalasani SB, Won E, Kelsen DP, Ilson DH, Janjigian YY, Capanu M, Ku GY. Phase I/Ib study of crenolanib with ramucirumab and paclitaxel as second-line therapy for advanced esophagogastric adenocarcinoma. Cancer Chemother Pharmacol. 2022 Feb;89(2):255-265. doi: 10.1007/s00280-021-04384-1. Epub 2022 Jan 23.