Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Within 6-12 weeks after surgery, patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Placebo

Regorafenib

Yelena Janjigian

This randomized phase II trial studies how well regorafenib works in treating patients with cancer of the esophagus or gastroesophageal junction that has spread from where it started to nearby tissue or lymph nodes and have completed chemoradiation therapy and surgery. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To compare the disease-free survival (DFS) for patients with resected esophageal and gastroesophageal (GE) junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.

SECONDARY OBJECTIVES:

I. To compare the safety profile of adjuvant regorafenib vs. placebo in patients with locally advanced resectable esophageal and GE junction adenocarcinoma.

II. To compare the overall survival (OS) for patients with resected esophageal and GE junction adenocarcinoma treated with regorafenib vs. placebo in the adjuvant setting.

III. To compare the DFS in those patients that receive at least 1 cycle of therapy.

IV. To collect tumor samples for future genomic analysis to explore the biology of locally advanced esophageal and GE junction adenocarcinoma.

V. DFS will be compared between the arms from the time of surgery as well.

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

ARM I: Within 6-12 weeks after surgery, patients receive regorafenib orally (PO) once daily (QD) on days 1-21.

ARM II: Within 6-12 weeks after surgery, patients receive placebo PO QD on days 1-21.

In both arms, courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, and every 6 months for up to 5 years.

Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery

Randomized Phase II Double Blind Study of Adjuvant Regorafenib vs Placebo in Patients With Node Positive Esophageal Cancer That Completed Pre-operative Therapy

Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause. The distribution of DFS will be estimated using the Kaplan Meier method.

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Overall survival (OS) is defined as the time from randomization to death due to any cause.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

The descriptions \& grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated.

Within 6-12 weeks after surgery, patients receive regorafenib OR placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Arm I/II (Regorafenib/Placebo)

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated.

Yelena Y. Janjigian MD

Only 1 patient was registered to the placebo arm. Due to protected health information, listing only 1 patient's results is contraindicated. The data below is descriptive and shouldn't be trusted because of the small sample size.

Disease Free Survival (DFS)

Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)

Overall Survival (OS)

Within 6-12 weeks after surgery, patients will receive regorafenib PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Arm I (Regorafenib)

Within 6-12 weeks after surgery, patients will receive placebo PO QD on days 1-21. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Arm II (Placebo)

Overall Study

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.

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

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery	NCT02234180	Adenocarcinoma ... Stage IIB Esoph... Stage IIIA Esop... Stage IIIB Esop... Stage IIIC Esop...	Placebo Regorafenib	18 Years -	Academic and Community Cancer Research United
Regorafenib in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction Who Have Completed Chemoradiation Therapy and Surgery	NCT02234180	Adenocarcinoma ... Stage IIB Esoph... Stage IIIA Esop... Stage IIIB Esop... Stage IIIC Esop...	Placebo Regorafenib	18 Years -	Academic and Community Cancer Research United
Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy	NCT02392377	Stage IB Esopha... Stage IIA Esoph... Stage IIB Esoph... Stage IIIA Esop... Stage IIIB Esop... Stage IIIC Esop...	Paclitaxel Carboplatin Oxaliplatin Leucovorin Calc... Fluorouracil Radiation Thera... Therapeutic Con... Laboratory Biom...	18 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for stage iib esophageal adenocarcinoma