Study of Crenolanib With Ramucirumab and Paclitaxel for Advanced Esophagogastric Adenocarcinoma

Esophagogastric Adenocarcinoma Clinical Trial

Official title:

Phase I/Ib Study of Crenolanib With Ramucirumab and Paclitaxel as Second Line Therapy for Advanced Esophagogastric Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03193918
• Other study ID #: ARO-017
• Status: Completed
• Phase: Phase 1
• Start date: April 14, 2017
• Est. completion date: July 15, 2020

Study information

• Verified date: July 2020
• Source: Arog Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 15, 2020
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophagogastric Adenocarcinoma

Intervention

Drug:
• Crenolanib
Crenolanib continuously on Days 1-28 at 1 of 3 BID doses - 60 mg, 80 mg or 100 mg
• Ramucirumab
Ramucirumab IV 8 mg/kg on Days 1 and 15 q28 days
• Paclitaxel
Paclitaxel IV 80 mg/m2 on Days 1, 8 and 15 q28 days

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Arog Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	5 weeks
Primary	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.