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

NCT02392377 | Terminated Phase 2 Results

• 6 other identifiers: CASE9314NCI-2015-00034CASE 9314K12CA076917P50CA150964P30CA043703
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (3)

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

  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

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

  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.

  Baseline

• Biological Pathway Perturbation Upon Exposure to Chemotherapy

  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.

  Up to 6 weeks

Secondary Outcomes (7)

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

  Baseline to post-induction (36-43 days)

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

  Baseline to post-induction (36-43 days)

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

  Baseline

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

  Baseline

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

  Baseline to post-induction (36-43 days)

Study Arms (2)

Arm I (paclitaxel, carboplatin, radiation therapy, surgery)

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Carboplatin; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis

Arm II (combination chemotherapy, radiation therapy, surgery)

EXPERIMENTAL

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.

Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Fluorouracil; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis

Interventions

Paclitaxel DRUG

Given IV or IVPB

Also known as: Anzatax, TAX

Arm I (paclitaxel, carboplatin, radiation therapy, surgery)

Carboplatin DRUG

Given IV or IVPB

Arm I (paclitaxel, carboplatin, radiation therapy, surgery)

Oxaliplatin DRUG

Given IV

Arm II (combination chemotherapy, radiation therapy, surgery)

Leucovorin Calcium DRUG

Given IV

Also known as: CF

Arm II (combination chemotherapy, radiation therapy, surgery)

Fluorouracil DRUG

Given IV

Arm II (combination chemotherapy, radiation therapy, surgery)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RT

Arm I (paclitaxel, carboplatin, radiation therapy, surgery); Arm II (combination chemotherapy, radiation therapy, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo esophagectomy

Arm I (paclitaxel, carboplatin, radiation therapy, surgery); Arm II (combination chemotherapy, radiation therapy, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (paclitaxel, carboplatin, radiation therapy, surgery); Arm II (combination chemotherapy, radiation therapy, surgery)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus

Interventions

Paclitaxel; Taxes; Carboplatin; Oxaliplatin; Leucovorin; Fluorouracil; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Dr Jennifer Eads
• Organization: University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

jennifer.eads@uhhospitals.org

(216) 844-6031

Study Officials

• Jennifer Eads

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2015
• First Posted: March 19, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 13, 2018
• Results First Posted: February 13, 2018

Record last verified: 2018-01

Locations

US (1)