Everolimus in Treating Patients With Previously Treated Unresectable or Metastatic Esophageal Cancer or Stomach Cancer

Gastric Cancer Clinical Trial

Official title:

A Phase II Study of the mTOR Inhibitor RAD001 in Previously Treated Patients With Unresectable or Metastatic Adenocarcinoma of the Esophagus and Stomach

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00985192
• Other study ID #: CDR0000655574
• Secondary ID: UCLA-TRIO-TORI-G
• Status: Completed
• Phase: Phase 2
• Start date: September 2009
• Est. completion date: May 2014

Study information

• Verified date: February 2016
• Source: Translational Oncology Research International
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with previously treated unresectable or metastatic esophageal cancer or stomach cancer.

Description:

OBJECTIVES:

Primary

• To determine the overall disease-control rate (complete response, partial response, or stable disease) in patients with previously treated unresectable or metastatic adenocarcinoma of the upper gastrointestinal tract treated with everolimus.

Secondary

• To determine the safety and toxicity of everolimus in these patients.

• To determine the efficacy of everolimus, in terms of time to response, duration of response, time to tumor progression, progression-free survival, and overall survival, in these patients.

• To explore potential correlations between clinical outcome and biomarkers of interest, including S6 protein overexpression and/or other mTOR-related proteins in blood and tumor biopsy samples from these patients.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Blood, serum, and tumor tissue samples are collected for biomarker analysis.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Diagnosis of adenocarcinoma of the upper gastrointestinal tract

• Metastatic or unresectable disease

• Received 1-2 prior chemotherapy or biological therapy regimens for unresectable or metastatic disease

• Measurable disease in = 1 dimension by CT scan or MRI

• Patients whose only measurable lesion is a metastatic lymph node are eligible provided they have permission from the principal investigator

• ECOG performance status 0-1

• Life expectancy > 3 months

• ANC = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9 g/dL

• Total bilirubin = 1.5 times upper limit of normal (ULN)

• AST and ALT = 2.5 times ULN (= 5.0 times ULN if there is liver metastasis)

• Creatinine clearance > 60 mL/min

• Fasting serum cholesterol < 300 mg/dL or < 7.75 mmol/L*

• Fasting triglycerides < 2.5 times ULN*

• INR = 3.5 (for patients on warfarin)

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 4 months after completion of study treatment (oral, implantable, or injectable contraceptives are not considered effective contraception for this study)

• More than 30 days since prior chemotherapy, surgery, radiotherapy, or investigational agents

Exclusion Criteria:

• uncontrolled diabetes mellitus, defined as fasting serum glucose > 1.5 times ULN

• severely impaired lung function

• known HV infection

• active, bleeding diathesis

• unstable angina pectoris, symptomatic congestive heart failure, or myocardial infarction within the past 6 months

• serious uncontrolled cardiac arrhythmia

• active or uncontrolled infection requiring parenteral antimicrobials

• known liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent hepatitis)

• inability to swallow, impaired gastrointestinal (GI) function, or GI disease (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) that would significantly alter the absorption of study drugs or preclude the use of oral medications

• other malignancy within the past 5 years except for nonmelanoma skin cancer or cervical carcinoma in situ

• known hypersensitivity to everolimus, sirolimus, or temsirolimus or to their excipients

• other medical conditions that, in the opinion of the investigator, would preclude study participation

• prior mTOR inhibitors (e.g., rapamycin, CCI-779)

• concurrent chronic treatment with steroids or another immunosuppressive agent

• concurrent prophylactic use of hematopoietic growth factors

• concurrent anticancer agents or therapy (including radiotherapy)

• other concurrent experimental agents

• concurrent strong inhibitors or inducers of the isoenzyme CYP3A4

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• everolimus

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Central Hematology Oncology Medical Group, Inc.	Alhambra	California
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center	Fullerton	California
United States	Antelope Valley Cancer Center	Lancaster	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Suburban Hematology-Oncology Associates, P.A.	Lawrenceville	Georgia
United States	Pacific Shores Medical Group	Long Beach	California
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	Translational Oncology Research International (TORI) Network	Los Angeles	California
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	North Valley Hematology/Oncology Medical Group	Northridge	California
United States	Wilshire Oncology Medical Group, Inc.	Pomona	California
United States	Cancer Care Associates Medical Group, Inc.	Redondo Beach	California
United States	TORI REDONDO BEACH (Cancer Care Associates Medical Group, Inc.)	Redondo Beach	California
United States	Sansum Medical Clinic	Santa Barbara	California
United States	Santa Barbara Hematology Oncology Medical Group, Inc.	Santa Barbara	California
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	Trivalley Oncology Hematology	Westlake Village	California

Sponsors (3)

Lead Sponsor	Collaborator
Translational Oncology Research International	National Cancer Institute (NCI), University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Disease-control Rate in Patients With Previously Treated Unresectable or Metastatic Adenocarcinoma of the Upper Gastrointestinal Tract Treated With Everolimus.	Disease control rate (DCR), defined as complete response (CR) + partial response (PR) + stable disease (SD) according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria.	Radiologic disease assessment was performed every 8 weeks (14 days = 1 cycle) treatment discontinuation.
Secondary	Overall Survival	Overall Survival (OS), defined as the time from date of initial treatment to date of death. Survival function was estimated using the Kaplan-Meier method.	2.5 year
Secondary	Efficacy in Terms of Progression Free Response	Progression-free survival (PFS), was defined as the time from the date of initial treatment to first objective documentation of disease progression, or death. Estimated using the Kaplan-Meier method. Complete response (CR) + partial response (PR) + stable disease (SD) were determined according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Radiologic disease assessments were utilized.	evry 3 months in year 1, every 6 months after that
Secondary	Observed Biomarkers	Potential correlations between clinical outcome and biomarkers of interest, including S6 protein overexpression and/or other mTOR-related proteins in tumor tissue samples from these patients.	30 months
Secondary	Biomarker Correlations: Progression Free Survival	Potential correlations between progression free survival and S6 protein and mTOR-related proteins in tumor tissue samples from these patients.	30 months
Secondary	Biomarker Correlations: Time to Progression	Potential correlations between time to progression and S6 protein and mTOR-related proteins in tumor tissue samples from these patients.	30 months