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

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Esophageal Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: everolimus

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 Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Alhambra, California, United States, 91801
      • Central Hematology Oncology Medical Group, Inc.
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center
    • Lancaster, California, United States, 93534
      • Antelope Valley Cancer Center
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90095
      • Translational Oncology Research International (TORI) Network
    • Northridge, California, United States, 91328
      • North Valley Hematology/Oncology Medical Group
    • Pomona, California, United States, 91767
      • Wilshire Oncology Medical Group, Inc.
    • Redondo Beach, California, United States, 90277
      • Cancer Care Associates Medical Group, Inc.
    • Redondo Beach, California, United States, 90277
      • TORI REDONDO BEACH (Cancer Care Associates Medical Group, Inc.)
    • Santa Barbara, California, United States, 93105
      • Sansum Medical Clinic
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Hematology Oncology Medical Group, Inc.
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation
    • Westlake Village, California, United States, 91361
      • Trivalley Oncology Hematology
  • Georgia
    • Lawrenceville, Georgia, United States, 30045
      • Suburban Hematology-Oncology Associates, P.A.
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, P.C.
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Comprehensive Cancer Centers of Nevada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Other: laboratory biomarker analysis; Drug: everolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Translational Oncology Research International
• Collaborators: National Cancer Institute (NCI); University of California, Los Angeles
• Investigators: Principal Investigator: Zev A. Wainberg, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: September 25, 2009
• First Submitted That Met QC Criteria: September 25, 2009
• First Posted (Estimate): September 28, 2009

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: August 3, 2020
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: stage IV gastric cancer; recurrent gastric cancer; stage III gastric cancer; stage III esophageal cancer; adenocarcinoma of the stomach; adenocarcinoma of the esophagus; recurrent esophageal cancer; stage IV esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Neoplasms; Esophageal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CDR0000655574; UCLA-TRIO-TORI-GI-06; IRB# 09-07-061-01; NOVARTIS-UCLA-TRIO-TORI-GI-06