Clinical trial NCT00985192: Everolimus in Treating Patients With Previously Treated Unresectable or Metastatic Esophageal Cancer or Stomach Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Gastric Cancer
Keywords: adenocarcinoma of the esophagus
adenocarcinoma of the stomach
recurrent esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
recurrent gastric cancer
stage III gastric cancer
stage IV gastric cancer
Lead sponsor: Translational Oncology Research International
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: University of California, Los Angeles
First posted: 2009-09-28
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Disease-control Rate in Patients With Previously Treated Unresectable or Metastatic Adenocarcinoma of the Upper Gastrointestinal Tract Treated With Everolimus.
timeFrame: Radiologic disease assessment was performed every 8 weeks (14 days = 1 cycle) treatment discontinuation.
Secondary outcomes:
measure: Overall Survival
timeFrame: 2.5 year
measure: Efficacy in Terms of Progression Free Response
timeFrame: evry 3 months in year 1, every 6 months after that
measure: Observed Biomarkers
timeFrame: 30 months
measure: Biomarker Correlations: Progression Free Survival
timeFrame: 30 months
measure: Biomarker Correlations: Time to Progression
timeFrame: 30 months
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Medical Group at Virginia K. Crosson Cancer Center
state: California
city: Lancaster
country: United States
facility: Antelope Valley Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
city: Los Angeles
country: United States
facility: Translational Oncology Research International (TORI) Network
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group
state: California
city: Pomona
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group, Inc.
state: California
city: Redondo Beach
country: United States
facility: TORI REDONDO BEACH (Cancer Care Associates Medical Group, Inc.)
state: California
city: Santa Barbara
country: United States
facility: Sansum Medical Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc.
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Westlake Village
country: United States
facility: Trivalley Oncology Hematology
state: California
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates, P.A.
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, P.C.
state: Georgia
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Zev A. Wainberg, MD
role: PRINCIPAL_INVESTIGATOR
References: