Clinical trial NCT01355302: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Solid Tumors
Previously Untreated Gastric Cancer
Keywords: Cancer
Solid Tumors
Gastric
Phase I
Phase II
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2011-05-18
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Area Under The Concentration-Time Curve (AUC) From 0 to 24 Hours of Golvatinib
timeFrame: 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.
measure: Maximum Concentration (Cmax) of Golvatinib
timeFrame: 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.
measure: Number of Participants With a Treatment-Emergent Adverse Event (TEAE)
timeFrame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 1 year 1 month.
measure: Time to Maximum Concentration (Tmax) of Golvatinib
timeFrame: 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:
measure: Overall Response Rate (ORR)
timeFrame: Until disease progression or death for 3 years
measure: Time to Progression (TTP)
timeFrame: Until disease progression or death for 3 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - CASA
state: Arizona
city: Plantation
country: United States
facility: Boca Raton Clinical Research Associates, Inc
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprenhensive Cancer Center of Northwestern University
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Chapell Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Toledo
country: United States
facility: Mercy Cancer Centerr at St. Anne
state: Ohio
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncology Dispensary
city: St Petersburg
country: Russian Federation
facility: GOU VPO St-Petersburg SMA n/a Mechnikov Fed. Agen. of Healthcare and Social Developm.
city: St Petersburg
country: Russian Federation
facility: FSI "SRC of Oncology n. a. N.N.Petrov of Rosmedtekhnologiy"
city: Dnipropetrovsk
country: Ukraine
facility: SI Dnipropetrovsk Medical Academy of MOHU ch of Oncology and Medical Radiology
city: Donetsk
country: Ukraine
facility: Municipal Clinical Medical and Prophylactic Institution Donetsk Regional Antitumor Centre
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Center
city: Lviv
country: Ukraine
facility: Lviv State Oncol. Reg. Treatment and Diagnostic Center
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
state: Greater London
city: London
country: United Kingdom
facility: Sarah Cannon Research UK
state: Greater London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
Study officials:
affiliation: Quintiles, Inc.
name: Melissa Versola
role: STUDY_DIRECTOR
References: