Study of Crenolanib With Ramucirumab and Paclitaxel for Advanced Esophagogastric Adenocarcinoma

Sponsor

Arog Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03193918

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophagogastric Adenocarcinoma	Drug: Crenolanib Drug: Ramucirumab Drug: Paclitaxel	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 14, 2017

Actual Primary Completion Date :

Jul 15, 2020

Actual Study Completion Date :

Jul 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crenolanib combined with ramucirumab/paclitaxel	Drug: Crenolanib Crenolanib continuously on Days 1-28 at 1 of 3 BID doses - 60 mg, 80 mg or 100 mg Drug: Ramucirumab Ramucirumab IV 8 mg/kg on Days 1 and 15 q28 days Drug: Paclitaxel Paclitaxel IV 80 mg/m2 on Days 1, 8 and 15 q28 days

Arm

Intervention/Treatment

Experimental: Crenolanib combined with ramucirumab/paclitaxel

Drug: Crenolanib

Crenolanib continuously on Days 1-28 at 1 of 3 BID doses - 60 mg, 80 mg or 100 mg

Drug: Ramucirumab

Ramucirumab IV 8 mg/kg on Days 1 and 15 q28 days

Drug: Paclitaxel

Paclitaxel IV 80 mg/m2 on Days 1, 8 and 15 q28 days

Outcome Measures

Primary Outcome Measures

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

Arog Pharmaceuticals, Inc.

Investigators

Principal Investigator: Geoffrey Ku, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Arog Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT03193918

Other Study ID Numbers:

ARO-017

First Posted:

Jun 21, 2017

Last Update Posted:

Jul 20, 2020

Last Verified:

Jul 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 20, 2020