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

Phase 2

Completed

• Conditions: Esophageal Cancer; Gastric Cancer
• Interventions: Drug: everolimus; Other: laboratory biomarker analysis

• Registration Number: NCT00985192
• Lead Sponsor: Translational Oncology Research International

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-25
• Study First Submitted QC: 2009-09-25
• Study First Posted: 2009-09-28
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2016-01-29
• Status Verified: 2016-02
• Results First Submitted QC: 2016-02-26
• Results First Posted: 2016-03-29
• Last Update Submitted: 2020-08-03
• Last Update Posted: 2020-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Everolimus	laboratory biomarker analysis	Patients receive oral everolimus once daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity
Everolimus	everolimus	Patients receive oral everolimus once daily on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity

Primary Outcome Measures

Name	Time	Method
Overall Disease-control Rate in Patients With Previously Treated Unresectable or Metastatic Adenocarcinoma of the Upper Gastrointestinal Tract Treated With Everolimus.	Radiologic disease assessment was performed every 8 weeks (14 days = 1 cycle) treatment discontinuation.	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2.5 year	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.
Efficacy in Terms of Progression Free Response	evry 3 months in year 1, every 6 months after that	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.
Observed Biomarkers	30 months	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.
Biomarker Correlations: Progression Free Survival	30 months	Potential correlations between progression free survival and S6 protein and mTOR-related proteins in tumor tissue samples from these patients.
Biomarker Correlations: Time to Progression	30 months	Potential correlations between time to progression and S6 protein and mTOR-related proteins in tumor tissue samples from these patients.

Trial Locations

Locations (18)

Antelope Valley Cancer Center; 🇺🇸 Lancaster, California, United States

Jonsson Comprehensive Cancer Center at UCLA; 🇺🇸 Los Angeles, California, United States

Santa Barbara Hematology Oncology Medical Group, Inc.; 🇺🇸 Santa Barbara, California, United States

Central Hematology Oncology Medical Group, Inc.; 🇺🇸 Alhambra, California, United States

Comprehensive Blood and Cancer Center; 🇺🇸 Bakersfield, California, United States

Translational Oncology Research International (TORI) Network; 🇺🇸 Los Angeles, 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

Central Coast Medical Oncology Corporation; 🇺🇸 Santa Maria, California, United States

Trivalley Oncology Hematology; 🇺🇸 Westlake Village, California, United States

St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center; 🇺🇸 Fullerton, California, United States

Northwest Georgia Oncology Centers, P.C.; 🇺🇸 Marietta, Georgia, United States

Sansum Medical Clinic; 🇺🇸 Santa Barbara, California, United States

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Wilshire Oncology Medical Group, Inc.; 🇺🇸 Pomona, California, United States

North Valley Hematology/Oncology Medical Group; 🇺🇸 Northridge, California, United States

Suburban Hematology-Oncology Associates, P.A.; 🇺🇸 Lawrenceville, Georgia, United States

Pacific Shores Medical Group; 🇺🇸 Long Beach, California, United States