Esophageal Cancer Clinical Trial
Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer
Summary
This randomized phase II trial studies how well paclitaxel with or without cixutumumab works in treating patients with esophageal cancer or gastroesophageal junction cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cixutumumab may kill cancer cells by blocking the action of a protein needed for cancer cell growth. Giving paclitaxel with or without cixutumumab may kill more tumor cells.
Full Description
PRIMARY OBJECTIVES:
I. To evaluate the progression-free survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone as second-line therapy in patients with metastatic esophagus or gastroesophageal (GE) junction cancer.
SECONDARY OBJECTIVES:
I. To evaluate the overall survival of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.
II. To evaluate the response rate of paclitaxel plus cixutumumab (IMC-A12) versus paclitaxel alone in this patient population.
III. To evaluate the toxicity of cixutumumab (IMC-A12) plus paclitaxel versus paclitaxel alone in this patient population.
IV. Exploratory analyses will assess potentially relevant cixutumumab (IMC-A12) pharmacodynamic biomarkers obtained from serum samples, including but not limited to, insulin-like growth factor (IGF)-I, IGF-II, insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-3.
OUTLINE: Patients are equally randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel intravenously (IV) over 1 hour at a dose of 80 mg/m^2 on days 1, 8, and 15 of every 28 day cycle.
ARM II: Patients receive cixutumumab IV over 1 hour at a dose of 10 mg/kg on days 1 and 15 of every 28 day cycle and paclitaxel as in Arm I.
In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Eligibility Criteria
Inclusion Criteria:
Life expectancy >= 12 weeks
Women must not be pregnant or breast-feeding due to potential harm to fetus from cixutumumab (IMC-A12) and paclitaxel; all females of childbearing potential must have a blood test or urine study within 48 hours prior to registration to rule out pregnancy
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method or birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of cixutumumab (IMC-A12); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Patients must have measurable disease
Patients must have metastatic disease of the esophagus or gastroesophageal junction
Histologic, cytologic or radiologic documentation of metastatic squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction; radiologic, endoscopic, histologic or cytologic evidence of locally recurrent or locally residual (post-resection) disease is also permitted
For the purposes of this study, undifferentiated adenocarcinomas and adenosquamous tumors will be considered as adenocarcinomas; in addition, tumors involving the gastroesophageal junction will be defined by the Siewert classification
Patients with gastroesophageal junction tumors who are eligible:
Adenocarcinoma of the esophageal junction (AEG) Type I: adenocarcinoma of the distal esophagus which usually arises from an area with specialized intestinal metaplasia of the esophagus, i.e., Barrett's esophagus, and may infiltrate the esophagogastric junction from above
AEG Type II: true carcinoma of the cardia arising from the cardiac epithelium or short segments with intestinal metaplasia at the esophagogastric junction
Patients with gastroesophageal junction tumors who are NOT eligible:
AEG Type III: subcardial gastric carcinoma which infiltrates the esophagogastric junction and distal esophagus from below
Patients must have received and progressed on one and only one line of prior systemic therapy for esophagus or esophagogastric cancer; this could have included one regimen for metastatic disease, or one regimen with radiotherapy for initially locally advanced disease; prior radiation therapy is permitted
If patients progress or recur within 6 months of neoadjuvant/adjuvant therapy, this will be considered one line of therapy; for patients progressing or recurring more than 6 months after neoadjuvant/adjuvant therapy, they will need to receive one line of therapy for recurrent disease to be eligible
If patients receive one regimen in which a chemotherapy agent is dropped for toxicity without progression, this treatment will be considered one line of therapy; however, substitution or addition of a new agent will be considered a second line of therapy
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Leukocytes > 3,000/mcL
Absolute neutrophil count >= 1,500/mcL
Hemoglobin >= 9 g/dL
Platelets >= 100,000/mcL
Total bilirubin =< institutional upper limit of normal (ULN)
Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional ULN
Creatinine =< 1.5 X institutional ULN or creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels above institutional normal
Patients must have fasting serum glucose =< 160 mg/dL (8.8 mmol/L) or =< ULN, and hemoglobin A1C =< 7% (0.07 International System of Units [SI units]) within 14 days of registration; if baseline nonfasting glucose =< 160 mg/dL (8.8 mmol/L), fasting glucose measurement is not required
Registration no fewer than 28 days from last chemotherapy
A "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse
Exclusion Criteria:
Patients have received prior taxane or anti-insulin growth factor receptor (IGFR) therapy
Patients must not have any of the following conditions:
Poorly controlled diabetes mellitus; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose =< 160 mg/dL [8.8 mmol/L] or below the ULN and hemoglobin A1C =< 7% [0.07 SI units]) and that they are on a stable dietary or therapeutic regimen for this condition
Recent major surgery, hormonal therapy (other than replacement) or chemotherapy, within 4 weeks prior to entering the study or those who have not recovered from adverse events
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cixutumumab (IMC-A12)
Psychiatric illness that would prevent the patient from giving informed consent
Medical conditions such as active/uncontrolled infection (including HIV) or cardiac disease that would make this protocol unreasonably hazardous for the patient in the opinion of the treating physician; cardiac disease may include uncontrolled high blood pressure, unstable angina, or serious uncontrolled cardiac arrhythmia
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There are 205 Locations for this study
Scottsdale Arizona, 85259, United States
Palo Alto California, 94304, United States
Aurora Colorado, 80012, United States
Boulder Colorado, 80301, United States
Colorado Springs Colorado, 80907, United States
Denver Colorado, 80210, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80220, United States
Denver Colorado, 80222, United States
Englewood Colorado, 80113, United States
Grand Junction Colorado, 81501, United States
Greeley Colorado, 80631, United States
Lakewood Colorado, 80228, United States
Littleton Colorado, 80122, United States
Lone Tree Colorado, 80124, United States
Longmont Colorado, 80501, United States
Loveland Colorado, 80539, United States
Parker Colorado, 80138, United States
Pueblo Colorado, 81004, United States
Thornton Colorado, 80229, United States
Wheat Ridge Colorado, 80033, United States
Hartford Connecticut, 06105, United States
Lewes Delaware, 19958, United States
Newark Delaware, 19718, United States
Jacksonville Florida, 32224, United States
Atlanta Georgia, 30322, United States
Savannah Georgia, 31405, United States
Boise Idaho, 83706, United States
Aurora Illinois, 60504, United States
Berwyn Illinois, 60402, United States
Bloomington Illinois, 61701, United States
Canton Illinois, 61520, United States
Carthage Illinois, 62321, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60611, United States
Decatur Illinois, 62526, United States
Decatur Illinois, 62526, United States
Eureka Illinois, 61530, United States
Galesburg Illinois, 61401, United States
Harvey Illinois, 60426, United States
Havana Illinois, 62644, United States
Highland Park Illinois, 60035, United States
Hinsdale Illinois, 60521, United States
Joliet Illinois, 60435, United States
Kankakee Illinois, 60901, United States
Libertyville Illinois, 60048, United States
Macomb Illinois, 61455, United States
Moline Illinois, 61265, United States
Naperville Illinois, 60563, United States
Niles Illinois, 60714, United States
Normal Illinois, 61761, United States
Normal Illinois, 61761, United States
Ottawa Illinois, 61350, United States
Pekin Illinois, 61554, United States
Peoria Illinois, 61614, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61636, United States
Peoria Illinois, 61637, United States
Peru Illinois, 61354, United States
Princeton Illinois, 61356, United States
River Forest Illinois, 60305, United States
Rockford Illinois, 61104, United States
Skokie Illinois, 60076, United States
Springfield Illinois, 62781, United States
Urbana Illinois, 61801, United States
Elkhart Indiana, 46515, United States
Indianapolis Indiana, 46202, United States
Indianapolis Indiana, 46202, United States
Indianapolis Indiana, 46202, United States
Indianapolis Indiana, 46219, United States
Kokomo Indiana, 46904, United States
La Porte Indiana, 46350, United States
Michigan City Indiana, 46360, United States
Mishawaka Indiana, 46545, United States
Muncie Indiana, 47303, United States
South Bend Indiana, 46601, United States
South Bend Indiana, 46628, United States
Ames Iowa, 50010, United States
Cedar Rapids Iowa, 52403, United States
Cedar Rapids Iowa, 52403, United States
Clive Iowa, 50325, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50316, United States
Mason City Iowa, 50401, United States
Sioux City Iowa, 51101, United States
Sioux City Iowa, 51102, United States
Sioux City Iowa, 51104, United States
Chanute Kansas, 66720, United States
Dodge City Kansas, 67801, United States
El Dorado Kansas, 67042, United States
Fort Scott Kansas, 66701, United States
Independence Kansas, 67301, United States
Kingman Kansas, 67068, United States
Lawrence Kansas, 66044, United States
Liberal Kansas, 67905, United States
McPherson Kansas, 67460, United States
Newton Kansas, 67114, United States
Parsons Kansas, 67357, United States
Pratt Kansas, 67124, United States
Salina Kansas, 67401, United States
Wellington Kansas, 67152, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Winfield Kansas, 67156, United States
Baton Rouge Louisiana, 70809, United States
New Orleans Louisiana, 70112, United States
New Orleans Louisiana, 70112, United States
Baltimore Maryland, 21287, United States
Elkton Maryland, 21921, United States
Adrian Michigan, 49221, United States
Adrian Michigan, 49221, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48106, United States
Dearborn Michigan, 48124, United States
Detroit Michigan, 48236, United States
Flint Michigan, 48503, United States
Flint Michigan, 48532, United States
Jackson Michigan, 49201, United States
Kalamazoo Michigan, 49007, United States
Kalamazoo Michigan, 49007, United States
Kalamazoo Michigan, 49048, United States
Lansing Michigan, 48912, United States
Livonia Michigan, 48154, United States
Monroe Michigan, 48162, United States
Monroe Michigan, 48162, United States
Pontiac Michigan, 48341, United States
Port Huron Michigan, 48060, United States
Saginaw Michigan, 48601, United States
Saint Joseph Michigan, 49085, United States
Saint Joseph Michigan, 49085, United States
Warren Michigan, 48093, United States
Brainerd Minnesota, 56401, United States
Burnsville Minnesota, 55337, United States
Coon Rapids Minnesota, 55433, United States
Duluth Minnesota, 55805, United States
Duluth Minnesota, 55805, United States
Duluth Minnesota, 55805, United States
Edina Minnesota, 55435, United States
Fridley Minnesota, 55432, United States
Hutchinson Minnesota, 55350, United States
Maplewood Minnesota, 55109, United States
Maplewood Minnesota, 55109, United States
Minneapolis Minnesota, 55407, United States
Minneapolis Minnesota, 55415, United States
New Ulm Minnesota, 56073, United States
Robbinsdale Minnesota, 55422, United States
Rochester Minnesota, 55905, United States
Saint Louis Park Minnesota, 55416, United States
Saint Louis Park Minnesota, 55416, United States
Saint Paul Minnesota, 55101, United States
Saint Paul Minnesota, 55102, United States
Shakopee Minnesota, 55379, United States
Stillwater Minnesota, 55082, United States
Waconia Minnesota, 55387, United States
Willmar Minnesota, 56201, United States
Woodbury Minnesota, 55125, United States
Lincoln Nebraska, 68510, United States
Omaha Nebraska, 68106, United States
Omaha Nebraska, 68122, United States
Omaha Nebraska, 68124, United States
Omaha Nebraska, 68130, United States
Omaha Nebraska, 68131, United States
Camden New Jersey, 08103, United States
East Orange New Jersey, 07018, United States
Freehold New Jersey, 07728, United States
Hamilton New Jersey, 08690, United States
New Brunswick New Jersey, 08903, United States
Newark New Jersey, 07101, United States
Newark New Jersey, 07112, United States
Albany New York, 12208, United States
Fargo North Dakota, 58103, United States
Akron Ohio, 44304, United States
Bowling Green Ohio, 43402, United States
Canton Ohio, 44708, United States
Cleveland Ohio, 44109, United States
Clyde Ohio, 43410, United States
Elyria Ohio, 44035, United States
Elyria Ohio, 44035, United States
Lima Ohio, 45801, United States
Lima Ohio, 45804, United States
Maumee Ohio, 43537, United States
Maumee Ohio, 43537, United States
Norwalk Ohio, 44857, United States
Oregon Ohio, 43616, United States
Oregon Ohio, 43616, United States
Sandusky Ohio, 44870, United States
Sylvania Ohio, 43560, United States
Tiffin Ohio, 44883, United States
Toledo Ohio, 43606, United States
Toledo Ohio, 43608, United States
Toledo Ohio, 43614, United States
Toledo Ohio, 43617, United States
Toledo Ohio, 43623, United States
Toledo Ohio, 43623, United States
Wauseon Ohio, 43567, United States
Bethlehem Pennsylvania, 18015, United States
Bryn Mawr Pennsylvania, 19010, United States
Butler Pennsylvania, 16001, United States
Danville Pennsylvania, 17822, United States
Hazleton Pennsylvania, 18201, United States
Paoli Pennsylvania, 19301, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19111, United States
Pittsburgh Pennsylvania, 15232, United States
Pottstown Pennsylvania, 19464, United States
Scranton Pennsylvania, 18508, United States
State College Pennsylvania, 16801, United States
West Reading Pennsylvania, 19611, United States
Wilkes-Barre Pennsylvania, 18711, United States
Wynnewood Pennsylvania, 19096, United States
Wynnewood Pennsylvania, 19096, United States
Jackson Tennessee, 38301, United States
Fredericksburg Virginia, 22401, United States
Wheeling West Virginia, 26003, United States
Antigo Wisconsin, 54409, United States
Green Bay Wisconsin, 54301, United States
Johnson Creek Wisconsin, 53038, United States
La Crosse Wisconsin, 54601, United States
Madison Wisconsin, 53715, United States
Madison Wisconsin, 53792, United States
Manitowoc Wisconsin, 54221, United States
Marinette Wisconsin, 54143, United States
Sheboygan Wisconsin, 53081, United States
Wausau Wisconsin, 54401, United States
Wisconsin Rapids Wisconsin, 54494, United States
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