Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Bone Density Conservation Agents

Hematinics

Vitamins

Paclitaxel

Albumin-Bound Paclitaxel

Oxaliplatin

Carboplatin

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Calcium, Dietary

Tubulin Modulators

Antimitotic Agents

Hormones

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

INDUCTION: Patients receive chemotherapy with carboplatin and paclitaxel. Patients receive carboplatin (AUC=2) and paclitaxel (90 mg/m2) intravenously on days 1 and 8 of a 21 day treatment cycle for two cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive carboplatin (AUC=2) and paclitaxel (50 mg/m2) intravenously once weekly for five weeks throughout the duration of their radiation which is daily (Monday through Friday).

SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

INDUCTION: Patients receive mFOLFOX6 where they get oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin 400 mg/m2 IV on day 1, 5-FU 400 mg/m2 IV on day 1 and then 5FU at 2400 mg/m2 IV to be administered over a 46 hour period. This is repeated every 2 weeks for 3 cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive oxaliplatin 85 mg/m2 IV on day 1 every 2 weeks for a total of 3 cycles (6 weeks) as well as 5FU 300 mg/m2/day over 96 hours via continuous infusion each week of radiation for a total of 6 weeks.

SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

Leucovorin Calcium

Radiation Therapy

Therapeutic Conventional Surgery

Laboratory Biomarker Analysis

Jennifer Eads

This randomized pilot phase II trial studies how well molecular phenotyping works in predicting response in patients with stage IB-III esophageal cancer who are receiving carboplatin and paclitaxel or oxaliplatin, leucovorin calcium, and fluorouracil. Studying the genes in a patients tumor cells before and after chemotherapy may help in understanding if there are specific features of the tumor cells that make a person more or less likely to respond to treatment and how these features may be affected by treatment.

PRIMARY OBJECTIVES:

I. To evaluate gene and micro ribonucleic acid (miRNA) expression levels in patients with esophageal adenocarcinoma prior to receiving chemotherapy and identify relative expression differences between patients responding and not responding to treatment with carboplatin and paclitaxel or 5-fluorouracil (fluorouracil) and oxaliplatin as measured by fluorodeoxyglucose F-18 (\[18F\] FDG)-positron emission tomography (PET).

SECONDARY OBJECTIVES:

I. To evaluate the impact of treatment on expression patterns of both genes and miRNAs in patients with esophageal adenocarcinoma following treatment with either carboplatin and paclitaxel or 5-fluorouracil and oxaliplatin, and identify expression patterns associated with treatment response and resistance as assessed by (18F) FDG-PET.

II. To evaluate the expression patterns of genes and miRNAs in patients with esophageal adenocarcinoma prior to and following a full neoadjuvant combined-modality treatment program with either carboplatin and paclitaxel or 5-fluorouracil and oxaliplatin chemotherapy plus radiation, and identify relative expression differences between patients achieving a pathologic complete response and patients not achieving a pathologic complete response.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION: Patients receive carboplatin (IV) and paclitaxel intravenously (IV) on days 1 and 8 of a 21 day cycle for two cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive carboplatin (AUC=2) and paclitaxel (50 mg/m2) intravenously once weekly for five weeks throughout the duration of their radiation which is daily (Monday through Friday). This will be given in combination with radiation therapy to a total of 50.4Gy using 180cGy fractions.

ARM II:

INDUCTION: Patients receive mFOLFOX6 where they get oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin 400 mg/m2 IV on day 1, 5-FU 400 mg/m2 IV on day 1 and then 5FU at 2400 mg/m2 IV to be administered over a 46 hour period. This is repeated every 2 weeks for 3 cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive chemoradiation with oxaliplatin 85 mg/m2 IV on day 1 every 2 weeks for a total of 3 cycles (6 weeks) as well as 5FU 300 mg/m2/day over 96 hours via continuous infusion each week of radiation for a total of 6 weeks. This will be given in combination with radiation therapy to a total of 50.4Gy using 180cGy fractions.

SURGERY: In both arms, approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

After completion of study treatment, patients are followed up at 30 days and then periodically thereafter.

Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

Pilot Study of Correlation Between Molecular Phenotype and Response to Two Independent Treatment Regimens, Carboplatin and Paclitaxel vs. 5-Fluorouracil and Oxaliplatin Chemotherapy in Patients With Localized Esophageal Adenocarcinoma

Baseline gene profiles will be compared for 10 (18F) FDG-PET responders vs. 15 (18F) FDG-PET non-responders per treatment regimen using a t-test and p-values will be corrected for multiple comparisons by calculating the false discovery rate (FDR) p-value (filtering on a FDR p-value \< 0.05). Top genes identified will be tested in combination for their sensitivity and specificity using logistic regression models.

Baseline microRNA profiles will be compared for 10 (18F) FDG-PET responders vs. 15 (18F) FDG-PET non-responders per treatment regimen using a t-test and p-values will be corrected for multiple comparisons by calculating the FDR p-value (filtering on a FDR p-value \< 0.05). Top microRNAs identified will be tested in combination for their sensitivity and specificity using logistic regression models.

Predefined signatures of biological pathway activities will be evaluated in order to identify pathway perturbation upon exposure to chemotherapy. Significant pathway modulations upon brief exposure will then be evaluated for association with clinical response using non-parametric tests such as the Wilcoxon signed-rank test. In all cases, statistical correction to account for multiple hypothesis testing will be employed and pathways with a false discovery rate of 10% or lower will be considered as significant.

Changes in baseline and post-treatment gene expression levels will be calculated between (18F) FDG-PET responders and non-responders, filtering for expression level changes of \>= 0.20. Differences in expression level change per treatment regimen will be calculated using a t-test and p-values will be corrected for multiple comparisons by calculating FDR p-value (filtering on a FDR p-value \< 0.05). Top genes identified will be tested in combination for their sensitivity and specificity using logistic regression models to predict responsiveness or resistance to each individual treatment regimen.

Changes in baseline and post-treatment microRNA levels will be calculated between (18F) FDG-PET responders and non-responders, filtering for expression level changes of \>= 0.20. Differences in expression level change per treatment regimen will be calculated using a t-test and p-values will be corrected for multiple comparisons by calculating FDR p-value (filtering on a FDR p-value \< 0.05). Top microRNAs identified will be tested in combination for their sensitivity and specificity using logistic regression models to predict responsiveness or resistance to each individual treatment regimen.

Baseline gene expression profiles for 8 pathologic complete responders vs. 17 patients not achieving a pathologic complete response per treatment regimen using a t-test will be compared. Top genes will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

Baseline microRNA profiles for 8 pathologic complete responders vs. 17 patients not achieving a pathologic complete response per treatment regimen using a t-test will be compared. Top microRNAs will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

Changes in baseline and post-treatment gene expression level/profiles will be compared between 8 pathologic responders vs. 17 patients not achieving a pathologic complete response per treatment regimen, filtering for expression levels changes of 0.20 and above. Differences in expression level changes per treatment regimen will be calculated using a t-test. Top genes will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

Changes in baseline and post-treatment microRNA level/profiles will be compared between 8 pathologic responders vs. 17 patients not achieving a pathologic complete response per treatment regimen, filtering for expression levels changes of 0.20 and above. Differences in expression level changes per treatment regimen will be calculated using a t-test. Top microRNAs will be tested in combination for their sensitivity and specificity using logistic regression models to predict achievement of a pathologic complete response vs. patients not achieving a pathologic complete response.

Toxicities will be summarized as the percentage of patients experiencing each type and grade of event according to treatment group. Patients who receive at least one dose of treatment will be included in the analysis.

National Cancer Institute (NCI)

Case Comprehensive Cancer Center

INDUCTION: Patients receive paclitaxel IV over 60 minutes and carboplatin intravenously IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

CHEMORADIATION THERAPY: Patients receive paclitaxel IVPB over 60 minutes and carboplatin IVPB over 30 minutes on days 8 and 22. Patients also undergo radiation therapy QD 5 days a week. Treatment continues for 5-6 weeks in the absence of disease progression or unacceptable toxicity.

SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

Paclitaxel: Given IV or IVPB

Carboplatin: Given IV or IVPB

Radiation Therapy: Undergo radiation therapy

Therapeutic Conventional Surgery: Undergo esophagectomy

Laboratory Biomarker Analysis: Correlative studies

Arm I (Paclitaxel, Carboplatin, Radiation Therapy, Surgery)

INDUCTION: Patients receive oxaliplatin IV over 2-6 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.

CHEMORADIATION THERAPY: Patients receive oxaliplatin IV over 2-6 hours on days 1, 15, and 29 and fluorouracil IV continuously over 96 hours on days 1, 8, 15, 22, and 29. Patients also undergo radiation therapy QD 5 days a week for 5-6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

Oxaliplatin: Given IV

Leucovorin Calcium: Given IV

Fluorouracil: Given IV

Radiation Therapy: Undergo radiation therapy

Therapeutic Conventional Surgery: Undergo esophagectomy

Laboratory Biomarker Analysis: Correlative studies

Arm II (Combination Chemotherapy, Radiation Therapy, Surgery)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Number of patients initially enrolled on study. 0 patients completed the study.

Dr Jennifer Eads

No patients completed study and no patients were enrolled on the comparison group arm. No analysis could be completed.

Relative Expression Differences in Individual Genes and Gene Profiles Between Patients Responding and Not Responding to Treatment, as Assessed by (18F) FDG-PET

Relative Expression Differences in Individual microRNAs and microRNA Profiles Between Patients Responding and Not Responding to Treatment, Assessed by (18F) FDG-PET

Biological Pathway Perturbation Upon Exposure to Chemotherapy

Relative Expression Differences Between Baseline and Post-induction Chemotherapy Specimens of Individual Genes and Gene Expression Profiles

Experimental: Arm I (paclitaxel, carboplatin, radiation therapy, surgery) INDUCTION: Patients receive chemotherapy with carboplatin and paclitaxel. Patients receive carboplatin (AUC=2) and paclitaxel (90 mg/m2) intravenously on days 1 and 8 of a 21 day treatment cycle for two cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive carboplatin (AUC=2) and paclitaxel (50 mg/m2) intravenously once weekly for five weeks throughout the duration of their radiation which is daily (Monday through Friday).

SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

Relative Expression Differences Between Baseline and Post-induction Chemotherapy Specimens of Individual microRNAs and microRNA Profiles

INDUCTION:Patients receive chemotherapy with carboplatin and paclitaxel. Patients receive carboplatin (AUC=2) and paclitaxel (90 mg/m2) intravenously on days 1 and 8 of a 21 day treatment cycle for two cycles (total of 6 weeks).

CHEMORADIATION THERAPY: Patients receive carboplatin (AUC=2) and paclitaxel (50 mg/m2) intravenously once weekly for five weeks throughout the duration of their radiation which is daily (Monday through Friday).

SURGERY: Approximately 4-10 weeks after completion of chemoradiation therapy, patients undergo esophagectomy at the discretion of the treating team.

Relative Expression Differences in Baseline Individual Genes and Gene Expression Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

Relative Expression Differences in Baseline Individual microRNAs and microRNA Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

Relative Expression Differences Between Baseline and Post-induction Gene Expression Levels/Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

Relative Expression Differences Between Baseline and Post-induction microRNA Levels/Profiles Between Patients Achieving and Not Achieving a Pathologic Complete Response Following Treatment

Spots Global Cancer Trial Database for stage ib esophageal adenocarcinoma