Back to resultsStudy of Crenolanib With Ramucirumab and Paclitaxel for Advanced Esophagogastric Adenocarcinoma
Primary Purpose
Esophagogastric Adenocarcinoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Crenolanib
Ramucirumab
Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Esophagogastric Adenocarcinoma
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
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Crenolanib combined with ramucirumab/paclitaxel
Arm Description
Outcomes
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.
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03193918
First Posted
June 14, 2017
Last Updated
July 17, 2020
Sponsor
Arog Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03193918
Brief Title
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
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
April 14, 2017 (Actual)
Primary Completion Date
July 15, 2020 (Actual)
Study Completion Date
July 15, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arog Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophagogastric Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Crenolanib combined with ramucirumab/paclitaxel
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Crenolanib
Intervention Description
Crenolanib continuously on Days 1-28 at 1 of 3 BID doses - 60 mg, 80 mg or 100 mg
Intervention Type
Drug
Intervention Name(s)
Ramucirumab
Intervention Description
Ramucirumab IV 8 mg/kg on Days 1 and 15 q28 days
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel IV 80 mg/m2 on Days 1, 8 and 15 q28 days
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
5 weeks
Title
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
Time Frame
Bi-monthly for up to 6 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geoffrey Ku, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35066693
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.
Results Reference
derived
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Study of Crenolanib With Ramucirumab and Paclitaxel for Advanced Esophagogastric Adenocarcinoma
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