Everolimus and Combination Chemotherapy in Treating Patients With Metastatic Stomach or Esophageal Cancer

NCT01231399 | Completed Phase 1 Results DMC

• 2 other identifiers: 10064NCI-2010-02168
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Everolimus may stop the growth of stomach or esophageal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Giving everolimus together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with combination chemotherapy in treating patients with metastatic stomach or esophageal cancer that has spread to other places in the body.

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD) of Everolimus

  The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

  Course 1 (first 28 days)

• Number of Subject With Overall Response

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Up to 5 years

• Progression-free Survival

  Estimated using the product-limit method of Kaplan and Meier. From the date treatment started until the date of first documented progression or date of death from any cause, whichever came first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  up to 5 years

• Overall Survival

  Estimated using the product-limit method of Kaplan and Meier. From the date treatment started until the date of death from any cause.

  Up to 5 years.

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive fluorouracil IV continuously over 46 hours, leucovorin calcium IV over 2 hours, and oxaliplatin IV over 2 hours on day 1. Patients also receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Drug: everolimus; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: microarray analysis

Interventions

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU, Adrucil, Efudex, FU

Arm I

leucovorin calcium DRUG

Given IV

Also known as: calcium folinate, CF, CFR, citrovorum factor, LV, Wellcovorin

Arm I

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, diaminocyclohexane oxalatoplatinum, Eloxatin, L-OHP

Arm I

everolimus DRUG

Given orally

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I

microarray analysis GENETIC

Correlative studies

Also known as: gene expression profiling

Arm I

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed diagnosis of gastric, esophageal, and GEJ adenocarcinoma
• Patients must have metastatic disease
• Patients must not have received any chemotherapy for metastatic disease
• Patients may have received prior adjuvant chemotherapy; completion of chemotherapy must be greater than 6 months from date of recurrent disease
• Patients must have computed tomography (CT) or magnetic resonance imaging (MRI) scan; patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
• Patients must have a ECOG Performance Status of 0-1
• Absolute neutrophil count (ANC) \> 1,500/mcl
• Platelet count \> 100,000/mcl
• Hemoglobin (Hg) \> 9 g/dL
• Serum creatinine \< 1.5 mg/dl and/or Creatinine clearance \> 60 cc/min
• Bilirubin \< 1.5 mg/dl
• Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamic pyruvic transaminase (SGPT) =\< 2.5 x institutional upper limit of normal (IULN) (=\< 5 x upper limit of normal \[ULN\] in patients with liver metastases)
• Fasting serum cholesterol =\< 300 mg/dL or =\< 7.75 mmol/L
• Fasting triglycerides =\< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
• Patients should have controlled diabetes as evidenced by hemoglobin (Hb)A1C =\< 8%

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc)
• Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus)
• Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids (prednisone \> 10 mg per day) or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• Severely impaired lung function as defined as spirometry and diffusion lung capacity of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN
• Active (acute or chronic) or uncontrolled severe infections
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

South Pasadena Cancer Center

South Pasadena, California, 91030, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms; Stomach Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Everolimus; Immunohistochemistry; Microarray Analysis; Gene Expression Profiling

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Sirolimus; Macrolides; Lactones; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Microchip Analytical Procedures; Genetic Techniques

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

(626) 218-5265

Study Officials

• Vincent Chung

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2010
• First Posted: November 1, 2010
• Study Start: February 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 31, 2017
• Results First Posted: May 31, 2017

Record last verified: 2017-04

Locations

US (3)