E7050 in Combination With Cisplatin and Capecitabine Versus Cisplatin and Capecitabine Alone in Patients With Advanced or Metastatic Solid Tumors and Previously Untreated Gastric Cancer

NCT01355302 | Terminated Phase 1 Results

• 2 other identifiers: E7050-7032011-000774-58
• Study Type: interventional
• Target: 7
• Locations: 4 countries
• Sites: 19

Brief Summary

The purpose of this study is to determine the following: 1. Find the maximum tolerated dose of E7050 when given in combination with cisplatin and capecitabine in patients with advance or metastatic solid tumors, and 2) Whether E7050 in combination with cisplatin and capecitabine is more effective in patients with previously untreated gastric cancer versus cisplatin and capecitabine alone.

Conditions

Advanced or Metastatic Solid Tumors; Previously Untreated Gastric Cancer

Keywords

Cancer; Solid Tumors; Gastric; Phase I; Phase II

Outcome Measures

Primary Outcomes (4)

• Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib

  On days when pharmacokinetic (PK) samples were to be drawn, a predose blood sample was obtained prior to administration of golvatinib and capecitabine. After administration of study drugs, a second postdose blood sample was taken. The amount of golvatinib in the participant's blood was analyzed and the AUC was calculated. The AUC reflects the actual body exposure to drug after administration of a dose of the drug and is dependent on the rate of elimination of the drug from the body and the dose administered. Predose samples that were below the limit of quantitation (BLQ) or missing were assigned a numerical value of zero for the calculation of AUC. Any other BLQ concentrations were assigned a value of zero. Results were expressed in nanograms·hour/milliter (ng·h/mL).

  Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.

• Maximum Concentration (Cmax) of Golvatinib

  Blood samples were drawn to analyze the amount of golvatinib in the participant's serum. Maximum concentration refers to the maximum (or peak) serum concentration of study drug in the participant's system after administration of the study drug and prior to the administration of a second dose of the study drug. Results were expressed in nanograms/milliliter (ng/mL).

  Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.

• Number of Participants With a Treatment-Emergent Adverse Event (TEAE)

  Safety assessments consisted of monitoring and recording all adverse events (AEs) and serious AEs; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an adverse event (AE) that had an onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to 30 days after the date of last study treatment.

  From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month.

• Time to Maximum Concentration (Tmax) of Golvatinib

  Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.

  Cycle 1 (Day -2); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), 24, and 48 hours after study treatment. Cycle 2 (Day 1); predose, 30 minutes, 1, 2, 3, 4, 8, 12 (if feasible), and 24 hours after study treatment.

Secondary Outcomes (2)

• Overall Response Rate (ORR)

  Until disease progression or death for 3 years

• Time to Progression (TTP)

  Until disease progression or death for 3 years

Study Arms (2)

Phase Ib: Cohort 1 and 2 and 3

EXPERIMENTAL

Phase Ib: Cohort 1; 200 mg E7050 + 80 mg/m2 cisplatin + 1000 mg/m2 capecitabine Cohort 2; 300 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine Cohort 3; 400 mg E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine

Drug: E7050; Drug: cisplatin; Drug: capecitabine

Phase II: Arm 1; E7050 + cisplatin+ capecitabine

ACTIVE COMPARATOR

Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine

Drug: E7050; Drug: cisplatin; Drug: capecitabine

Interventions

E7050 DRUG

E7050 given orally at either 200, 300, or 400 mg once daily.

Phase II: Arm 1; E7050 + cisplatin+ capecitabine; Phase Ib: Cohort 1 and 2 and 3

cisplatin DRUG

Cisplatin will be administered at 80 mg/m2 by intravenous infusion over 60 minutes on Day 1 of each 21-day treatment cycle.

Phase II: Arm 1; E7050 + cisplatin+ capecitabine; Phase Ib: Cohort 1 and 2 and 3

capecitabine DRUG

Capecitabine will be administered at 1000 mg/m2 orally, twice daily (2000 mg/m2 total daily dose) on Days 1 through 14 of each 21-day treatment cycle.

Phase II: Arm 1; E7050 + cisplatin+ capecitabine; Phase Ib: Cohort 1 and 2 and 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, unresectable, locally advanced or metastatic gastric cancer, including adenocarcinoma of the gastroesophageal junction (Phase II). For the Phase Ib portion, any unresectable, locally advanced or metastatic solid tumor;
• ECOG PS of 0-1;
• Blood pressure must be well-controlled. Patients must have no history of hypertensive crisis or hypertensive encephalopathy; Adequate end organ function

You may not qualify if:

• Gastric cancer patients who have had a complete gastrectomy;
• Patients with known HER2 over-expressing advanced or metastatic gastric cancer;
• Previously received E7050, its chemical derivatives, anti-cMet, anti-angiogenic therapy, (prior anti-angiogenic therapy is permitted in Phase Ib only).
• For Phase Ib prior systemic therapy is allowed as long as PS and end organ function meet entry criteria;
• For Phase II no prior palliative chemotherapy is permitted. Adjuvant/neoadjuvant chemotherapy is permitted if less than 12 months have elapsed between the end of adjuvant/neoadjuvant therapy and first recurrence;
• Known central nervous system lesions, except for asymptomatic non-progressing, treated brain metastases. Treatment for brain mets, but have been completed at least 4 weeks prior to Day 1
• Palliative radiotherapy is not permitted throughout the study period. Prior palliative radiotherapy within 30 days prior to commencing study treatment;
• Clinically significant hemoptysis;
• Patients with known dihydropyrimidine dehydrogenase deficiency;
• Patients with clinically significant hearing loss that may be further diminished by treatment with cisplatin plus capecitabine (significance of hearing loss to be determined by the Investigator;
• Serious non-healing wound, ulcer, or active bone fracture;
• Major surgical procedure, open biopsy, or significant traumatic injury within the 21 days prior to commencing study treatment;
• Clinically significant gastrointestinal bleeding within 6 months prior to first dose.

Sponsors & Collaborators

• Eisai Inc.: lead
• Quintiles, Inc.: collaborator

Study Sites (19)

Arizona Oncology Associates, PC - CASA

Tucson, Arizona, 85715, United States

Location

Boca Raton Clinical Research Associates, Inc

Plantation, Florida, 33324, United States

Location

Robert H. Lurie Comprenhensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48084, United States

Location

Henry Ford Medical Center

Detroit, Michigan, 48202, United States

Location

University of North Carolina at Chapel Hill

Chapell Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Mercy Cancer Centerr at St. Anne

Toledo, Ohio, 43623, United States

Location

Chelyabinsk Regional Oncology Dispensary

Chelyabinsk, 454087, Russia

Location

GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.

Saint Petersburg, 195067, Russia

Location

FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"

Saint Petersburg, 197758, Russia

Location

SI Dnipropetrovsk Medical Academy of MOHU ch of Oncology and Medical Radiology

Dnipropetrovsk, 49102, Ukraine

Location

Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre

Donetsk, 83092, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, 3115, Ukraine

Location

Lviv State Oncol. Reg. Treatment and Diagnostic Center

Lviv, 79031, Ukraine

Location

Barts and the London NHS Trust

London, Greater London, EC1A 7BE, United Kingdom

Location

Sarah Cannon Research UK

London, Greater London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

N-(2-fluoro-4-((2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)carbonylaminopyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; Cisplatin; Capecitabine

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study was terminated prior to enrollment in Phase 2.

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai Inc.

888-422-4743

Study Officials

• Melissa Versola

  Quintiles, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 18, 2011
• Study Start: November 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: July 1, 2013
• Last Updated: May 15, 2017
• Results First Posted: March 13, 2017

Record last verified: 2017-03

Locations

RU (3); UA (4); US (9); GB (3)