Study of Crenolanib With Ramucirumab and Paclitaxel for Advanced Esophagogastric Adenocarcinoma

Phase 1

Completed

• Conditions: Esophagogastric Adenocarcinoma
• Interventions: Drug: Crenolanib; Drug: Ramucirumab; Drug: Paclitaxel

• Registration Number: NCT03193918
• Lead Sponsor: Arog Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-04-14
• Study First Submitted: 2017-06-14
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-21
• Status Verified: 2020-07
• Primary Completion: 2020-07-15
• Study Completion: 2020-07-15
• Last Update Submitted: 2020-07-17
• Last Update Posted: 2020-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Crenolanib combined with ramucirumab/paclitaxel	Paclitaxel	-
Crenolanib combined with ramucirumab/paclitaxel	Crenolanib	-
Crenolanib combined with ramucirumab/paclitaxel	Ramucirumab	-

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States