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

NCT ID: NCT01355302

Last Updated: 2017-05-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-07-31

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.

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.

Conditions

Advanced or Metastatic Solid Tumors; Previously Untreated Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

E7050

Intervention Type: DRUG

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

cisplatin

Intervention Type: DRUG

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

capecitabine

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

Group Type: ACTIVE_COMPARATOR

E7050

Intervention Type: DRUG

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

cisplatin

Intervention Type: DRUG

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

capecitabine

Intervention Type: 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.

Interventions

E7050

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Versola

Role: STUDY_DIRECTOR

Quintiles, Inc.

Locations

Arizona Oncology Associates, PC - CASA

Tucson, Arizona, United States

Boca Raton Clinical Research Associates, Inc

Plantation, Florida, United States

Robert H. Lurie Comprenhensive Cancer Center of Northwestern University

Chicago, Illinois, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Henry Ford Medical Center

Detroit, Michigan, United States

University of North Carolina at Chapel Hill

Chapell Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Mercy Cancer Centerr at St. Anne

Toledo, Ohio, United States

Chelyabinsk Regional Oncology Dispensary

Chelyabinsk, , Russia

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

Saint Petersburg, , Russia

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

Saint Petersburg, , Russia

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

Dnipropetrovsk, , Ukraine

Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre

Donetsk, , Ukraine

Kyiv City Clinical Oncological Center

Kyiv, , Ukraine

Lviv State Oncol. Reg. Treatment and Diagnostic Center

Lviv, , Ukraine

Barts and the London NHS Trust

London, Greater London, United Kingdom

Sarah Cannon Research UK

London, Greater London, United Kingdom

The Christie NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Countries

United States; Russia; Ukraine; United Kingdom

Other Identifiers

2011-000774-58

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E7050-703

Identifier Type: -

Identifier Source: org_study_id