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

Advanced or Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01355302
• Other study ID #: E7050-703
• Secondary ID: 2011-000774-58
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: May 16, 2011
• Last updated: November 14, 2013
• Start date: November 2011
• Est. completion date: July 2013

Study information

• Verified date: November 2013
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 >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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Previously Untreated Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• E7050
E7050 given orally at either 200, 300, or 400 mg once daily.
• cisplatin
Cisplatin will be administered at 80 mg/m2 by intravenous infusion over 60 minutes on Day 1 of each 21-day treatment cycle.
• 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.

Locations

Country	Name	City	State
Russian Federation	Chelyabinsk Regional Oncology Dispensary	Chelyabinsk
Russian Federation	FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"	St Petersburg
Russian Federation	GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.	St Petersburg
Ukraine	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
United Kingdom	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 States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of North Carolina at Chapel Hill	Chapell Hill	North Carolina
United States	Robert H. Lurie Comprenhensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Boca Raton Clinical Research Associates, Inc	Plantation	Florida
United States	Mercy Cancer Centerr at St. Anne	Toledo	Ohio
United States	Arizona Oncology Associates, PC - CASA	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Eisai Inc.	Quintiles, Inc.

Countries where clinical trial is conducted

United States,  Russian Federation,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety parameter:adverse events	Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Advanced or Metastatic Solid Tumors; •Phase II: to evaluate the safety and tolerability of E7050 administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Previously Untreated Gastric Cancer.	until study termination; 3 years	Yes
Primary	Safety parameter:Concomitant medications	Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Advanced or Metastatic Solid Tumors; Phase II: to evaluate the safety and tolerability of E7050 administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Previously Untreated Gastric Cancer.	until study termination; 3 years	Yes
Primary	Safety parameter: lab tests	Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Advanced or Metastatic Solid Tumors; Phase II: to evaluate the safety and tolerability of E7050 administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Previously Untreated Gastric Cancer.	Day 1 and every 21 days until study termination; 3 years	Yes
Primary	Safety parameter: ECGs	Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Advanced or Metastatic Solid Tumors; Phase II: to evaluate the safety and tolerability of E7050 administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Previously Untreated Gastric Cancer.	Screening and 21 days after end of therapy; 3 years	Yes
Secondary	Efficacy parameter: Overall response rate (ORR)	Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Advanced or Metastatic Solid Tumors; Phase II: to evaluate the safety and tolerability of E7050 administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Previously Untreated Gastric Cancer.	Until disease progression or death for 3 years	No
Secondary	Efficacy parameter: Time to progression (TTP)	Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Advanced or Metastatic Solid Tumors; Phase II: to evaluate the safety and tolerability of E7050 administered in combination with Cisplatin and Capecitabine versus Cisplatin and Capecitabine Alone in Patients with Previously Untreated Gastric Cancer	Until disease progression or death for 3 years	No