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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

This study has been terminated.
(Sites not recruiting)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01355302
First Posted: May 18, 2011
Last Update Posted: May 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Eisai Inc.
  Purpose
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.

Condition Intervention Phase
Advanced or Metastatic Solid Tumors Previously Untreated Gastric Cancer Drug: E7050 Drug: cisplatin Drug: capecitabine Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized, Phase Ib/II Study of 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib [ Time Frame: 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. ]
    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).

  • Maximum Concentration (Cmax) of Golvatinib [ Time Frame: 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. ]
    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).

  • Number of Participants With a Treatment-Emergent Adverse Event (TEAE) [ Time Frame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month. ]
    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.

  • Time to Maximum Concentration (Tmax) of Golvatinib [ Time Frame: 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. ]
    Tmax was defined as the time at which Cmax was observed for golvatinib in combination with cisplatin and capecitabine.


Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: Until disease progression or death for 3 years ]
    The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.

  • Time to Progression (TTP) [ Time Frame: Until disease progression or death for 3 years ]
    The study was terminated prior to enrollment in Phase 2 so this outcome measure was not conducted.


Enrollment: 7
Study Start Date: November 2011
Study Completion Date: July 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase Ib: Cohort 1 and 2 and 3

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
E7050 given orally at either 200, 300, or 400 mg once daily.
Drug: cisplatin
Cisplatin will be administered at 80 mg/m2 by intravenous infusion over 60 minutes on Day 1 of each 21-day treatment cycle.
Drug: capecitabine
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.
Active Comparator: Phase II: Arm 1; E7050 + cisplatin+ capecitabine
Phase II: Arm 1; MTD E7050 + 80 mg/m2 cisplatin + 2000 mg/m2 capecitabine
Drug: E7050
E7050 given orally at either 200, 300, or 400 mg once daily.
Drug: cisplatin
Cisplatin will be administered at 80 mg/m2 by intravenous infusion over 60 minutes on Day 1 of each 21-day treatment cycle.
Drug: capecitabine
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.

Detailed Description:

This open-label, multicenter, randomized study will consist of 2 phases:

Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with fixed doses of Cisplatin and Capecitabine. This phase will enroll approximately 10 to 15 patients.

  • Phase II: a randomized 2-arm design which will enroll 80 patients.

In the phase II portion, Patients will receive study treatment , E7050 in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone) for approximately six 21-day cycles (18 weeks). Beyond 18 weeks, patients who are experiencing clinical benefit may continue E7050, with or without Capecitabine (Arm 1), or may continue Capecitabine alone (Arm 2), depending on the original randomization treatment arm. Patients will continue treatment for as long as clinical benefit is sustained and the treatment is well tolerated, until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, or withdrawal by investigator, whichever occurs first. Patients will participate in either phase Ib or phase II.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01355302


Locations
United States, Arizona
Arizona Oncology Associates, PC - CASA
Tucson, Arizona, United States, 85715
United States, Florida
Boca Raton Clinical Research Associates, Inc
Plantation, Florida, United States, 33324
United States, Illinois
Robert H. Lurie Comprenhensive Cancer Center of Northwestern University
Chicago, Illinois, United States, 60611
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48084
Henry Ford Medical Center
Detroit, Michigan, United States, 48202
United States, North Carolina
University of North Carolina at Chapel Hill
Chapell Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Mercy Cancer Centerr at St. Anne
Toledo, Ohio, United States, 43623
Russian Federation
Chelyabinsk Regional Oncology Dispensary
Chelyabinsk, Russian Federation, 454087
GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.
St Petersburg, Russian Federation, 195067
FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
St Petersburg, Russian Federation, 197758
Ukraine
SI Dnipropetrovsk Medical Academy of MOHU ch of Oncology and Medical Radiology
Dnipropetrovsk, Ukraine, 49102
Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre
Donetsk, Ukraine, 83092
Kyiv City Clinical Oncological Center
Kyiv, Ukraine, 3115
Lviv State Oncol. Reg. Treatment and Diagnostic Center
Lviv, Ukraine, 79031
United Kingdom
Barts and the London NHS Trust
London, Greater London, United Kingdom, EC1A 7BE
Sarah Cannon Research UK
London, Greater London, United Kingdom, W1G 6AD
The Christie NHS Foundation Trust
Manchester, Greater Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Eisai Inc.
Quintiles, Inc.
Investigators
Study Director: Melissa Versola Quintiles, Inc.
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01355302     History of Changes
Other Study ID Numbers: E7050-703
2011-000774-58 ( EudraCT Number )
First Submitted: May 16, 2011
First Posted: May 18, 2011
Results First Submitted: January 19, 2017
Results First Posted: March 13, 2017
Last Update Posted: May 15, 2017
Last Verified: March 2017

Keywords provided by Eisai Inc.:
Cancer
Solid Tumors
Gastric
Phase I
Phase II

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Cisplatin
Capecitabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action