NCT03193918

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Apr 2017

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 14, 2017

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

June 14, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 21, 2017

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 15, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 15, 2020

Completed
Last Updated

July 20, 2020

Status Verified

July 1, 2020

Enrollment Period

3.3 years

First QC Date

June 14, 2017

Last Update Submit

July 17, 2020

Conditions

Esophagogastric Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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.

Study Arms (1)

Crenolanib combined with ramucirumab/paclitaxel

EXPERIMENTAL
Drug: CrenolanibDrug: RamucirumabDrug: Paclitaxel

Interventions

CrenolanibDRUG

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

Crenolanib combined with ramucirumab/paclitaxel
RamucirumabDRUG

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

Crenolanib combined with ramucirumab/paclitaxel
PaclitaxelDRUG

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

Crenolanib combined with ramucirumab/paclitaxel

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

  • 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.

    PMID: 35066693DERIVED

MeSH Terms

Interventions

crenolanibRamucirumabPaclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • Geoffrey Ku, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 14, 2017

First Posted

June 21, 2017

Study Start

April 14, 2017

Primary Completion

July 15, 2020

Study Completion

July 15, 2020

Last Updated

July 20, 2020

Record last verified: 2020-07

Locations

US(1)