Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Stomach Neoplasms

Recurrence

Esophageal Squamous Cell Carcinoma

Esophageal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

10-deazaaminopterin

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Enzyme Inhibitors

Folinic Acid

Folate

Vitamin B9

Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.

Laboratory Biomarker Analysis

Pralatrexate

Nikhil Khushalani

This phase II trial studies how well pralatrexate and oxaliplatin work in treating patients with esophageal, stomach, or gastroesophageal junction cancer that cannot be removed by surgery or has spread from the primary site (place where it started) to other places in the body. Pralatrexate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, 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. Giving pralatrexate with oxaliplatin may be an effective treatment for esophageal, stomach, or gastroesophageal junction cancer.

PRIMARY OBJECTIVES:

I. To determine the overall response rate in patients with advanced esophago-gastric cancer (EGC) to combination pralatrexate and oxaliplatin.

SECONDARY OBJECTIVES:

I. To examine the toxicity and tolerability of this regimen. II. To determine the time-to-progression and overall survival using this regimen.

III. To examine whether functionally relevant polymorphisms of genes of the folate metabolism pathway correlate with efficacy and toxicity of pralatrexate.

IV. To examine whether response to pralatrexate can be predicted by micro-ribonucleic acid (microRNA) expression profiling of the epithelial component of the tumor.

OUTLINE:

Patients receive pralatrexate intravenously (IV) over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.

After completion of study treatment, patients are followed up for 30 days and then periodically thereafter for up to 5 years.

Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer

Pralatrexate in Combination With Oxaliplatin in Advanced Esophago-gastric Cancer: A Phase II Trial With Predictive Molecular Correlates

Kaplan-Meier estimates of median survival time for each genotype

Mean microRNAs expression of mi-215-5p in tumor tissues of responders and non-responders using a microfabricated device called a gene chip.

Overall response rate to combination pralatrexate and oxaliplatin as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Objective responses will be confirmed 4 weeks after first documentation of response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.

Number of participants with an adverse event. Please refer to the adverse event reporting for more detail. Incidence of toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

Estimated using the Kaplan-Meier method and proportional hazards models.

National Cancer Institute (NCI)

National Comprehensive Cancer Network

Roswell Park Cancer Institute

Patients receive pralatrexate IV over 3-5 minutes and oxaliplatin IV over 2 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Oxaliplatin will be discontinued after 12 courses.

Laboratory Biomarker Analysis: Correlative studies

Oxaliplatin: Given IV

Pralatrexate: Given IV

Treatment (Pralatrexate, Oxaliplatin)

Age, Continuous

Sex: Female, Male

Senior Administrator, Compliance - Clinical Research Services

All Cohort -1 treated and eligible patients

Overall Response Rate

Number of Participants With an Adverse Event

Overall Survival (OS)

Time to Progression (TTP)

Overall Survival (OS) for SNP ATIC/AICART - s10932606 Genotypes

Comparison is CR+PR vs stable disease/progression

Responders: CR+PR

Non responders: stable disease/progression

All treated participants that had enough tissue to perform microdissection to collect epithelial cells for subsequent microRNA profiling.

MicroRNA Expression - miR-215-5p

Overall Study

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Immunologic Factors

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.

Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.

Cixutumumab

Pharmacological Study

Steven J Cohen

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.

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.

Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

Randomized Phase II Study of Paclitaxel With or Without the Anti-IGF-IR mAb Cixutumumab (IMC-A12) as Second Line Treatment for Patients With Metastatic Esophageal or GE Junction Cancer

Progression-free survival (PFS) is defined as the time from randomization to progression or death without evidence of progression. For cases without documentation of progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was counted as an event, or in the case of death within 4 months of randomization in the absence of disease evaluation before that time. PFS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.

Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. OS was estimated using the Kaplan-Meier method, with 90% confidence intervals calculated using Greenwood's formula, and compared by the log rank test.

Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as disappearance of target lesions or at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

Late adverse events (defined as any adverse events that occur prior to diagnosis of progression/relapse and has not been previously reported) are collected via the long-term follow up form at each required follow-up visits.

Patients receive paclitaxel IV over 1 hour at a dose of 80 mg/m\^2 on days 1, 8, and 15 of every 28 day cycle.

paclitaxel: Given IV

Arm I (Paclitaxel)

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.

cixutumumab: Given IV, administered prior to chemotherapy, doses were based on actual body weight

paclitaxel: Given IV

Arm II (Cixutumumab, Paclitaxel)

Total

United States

Region of Enrollment

Per protocol, the primary population for all efficacy endpoints is all eligible patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer	NCT01178944	Adenocarcinoma ... Esophageal Undi... Gastric Adenoca... Gastric Squamou... Recurrent Esoph... Recurrent Esoph... Recurrent Gastr... Stage IIIB Esop... Stage IIIB Esop... Stage IIIB Gast... Stage IIIC Esop... Stage IIIC Esop... Stage IIIC Gast... Stage IV Esopha... Stage IV Esopha... Stage IV Gastri... Undifferentiate...	Laboratory Biom... Oxaliplatin Pralatrexate	18 Years -	Roswell Park Cancer Institute
Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer	NCT01142388	Metastatic Esop... Metastatic Esop... Metastatic Gast... Recurrent Esoph... Recurrent Esoph... Recurrent Esoph... Recurrent Gastr... Stage IV Esopha...	Cixutumumab Laboratory Biom... Paclitaxel Pharmacological...	18 Years -	National Cancer Institute (NCI)
Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer	NCT01178944	Adenocarcinoma ... Esophageal Undi... Gastric Adenoca... Gastric Squamou... Recurrent Esoph... Recurrent Esoph... Recurrent Gastr... Stage IIIB Esop... Stage IIIB Esop... Stage IIIB Gast... Stage IIIC Esop... Stage IIIC Esop... Stage IIIC Gast... Stage IV Esopha... Stage IV Esopha... Stage IV Gastri... Undifferentiate...	Laboratory Biom... Oxaliplatin Pralatrexate	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for recurrent esophageal adenocarcinoma