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

NCT ID: NCT02392377

Last Updated: 2018-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

Given IV or IVPB

Carboplatin

Intervention Type: DRUG

Given IV or IVPB

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo esophagectomy

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Arm II (combination chemotherapy, radiation therapy, surgery)

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.

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: DRUG

Given IV

Leucovorin Calcium

Intervention Type: DRUG

Given IV

Fluorouracil

Intervention Type: DRUG

Given IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo esophagectomy

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Paclitaxel

Given IV or IVPB

Intervention Type: DRUG

Carboplatin

Given IV or IVPB

Intervention Type: DRUG

Oxaliplatin

Given IV

Intervention Type: DRUG

Leucovorin Calcium

Given IV

Intervention Type: DRUG

Fluorouracil

Given IV

Intervention Type: DRUG

Radiation Therapy

Undergo radiation therapy

Intervention Type: RADIATION

Therapeutic Conventional Surgery

Undergo esophagectomy

Intervention Type: PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Anzatax; TAX; CF; Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; RT

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed localized (T1N1-3M0 or T2-4NanyM0, stage IB-III) Siewert type 1 or type 2 esophageal adenocarcinoma that is amenable to surgical resection as determined by a thoracic surgeon and for which all disease (primary tumor and involved lymph nodes) can be treated with radiation, as determined by a radiation oncologist
• Patients may not have received any prior chemotherapy, biologic therapy or radiation therapy for management of their disease; chemotherapy or biologic therapy administered for treatment of another primary malignancy are permitted if treatment was greater than 5 years ago
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patients must have a life expectancy of > 3 months, in the opinion of and as documented by the investigator
• Hemoglobin >= 10.0 g/dl
• Absolute neutrophil count >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Serum creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (as calculated by Cockcroft-Gault)
• Patients must have an avid primary tumor with an standardized uptake value (SUV) of >= 5 on baseline (18F) FDG-PET/computed tomography (CT) imaging
• Men must agree to use adequate contraception (double barrier method of birth control or abstinence) 1 week prior to study entry, for the duration of study participation and for 1 month after completing combined modality treatment with chemotherapy and radiation; should a male patient's female partner become pregnant or suspect that she is pregnant while her partner is participating in this study, the treating physician should be informed immediately
• Patients must have the ability to understand and the willingness to sign a written informed consent document
• This study will be limited to enrollment of Caucasian males only

Exclusion Criteria

• Patients who are receiving any chemotherapy, biologic therapy, radiation therapy or any investigational agent
• Patients with metastatic disease
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to platinums, taxanes or fluoropyrimidines
• Patients who have previously received radiation therapy to the chest or abdomen such that there would be overlap between the previous and current radiation field
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with human immunodeficiency virus (HIV) whom are not receiving antiretroviral therapy
• Patients with another malignancy within the past 5 years

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Eads

Role: PRINCIPAL_INVESTIGATOR

Case Comprehensive Cancer Center

Locations

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

NCI-2015-00034

Identifier Type: REGISTRY

Identifier Source: secondary_id

CASE 9314

Identifier Type: OTHER

Identifier Source: secondary_id

K12CA076917

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P50CA150964

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE9314

Identifier Type: -

Identifier Source: org_study_id