Neoplasms

All Conditions

Digestive System Diseases

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Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Quality of Life

Radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments. 1.8 Gy (or at RBE ("Relative Biologic Equivalence" for PBT)) to be delivered to the periphery of the planning target volume (PTV).

Radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments. 1.8 Gy to be delivered to the periphery of the planning target volume (PTV).

1.8 Gy (Relative Biologic Equivalence ((RBE)) to be delivered to the periphery of the planning target volume (PTV) 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments.

Proton Beam Therapy (PBT)

1.8 Gy to be delivered to the periphery of the planning target volume (PTV) 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments.

Intensity Modulated Radiation Therapy (IMRT)

Symptom and Quality of Life questionnaires completed at baseline, every week during radiation therapy, during break after radiation therapy, and during follow up phase.

Questionnaires

Steven H. Lin, MD,PHD

The goal of this clinical research study is to learn how safe and effective proton-beam therapy (PBT) may be in comparison to intensity modulated radiation therapy (IMRT) in combination with chemotherapy in patients with esophageal cancer.

PBT and IMRT are both forms of radiation therapy that are designed to treat a specific area of the body while affecting as little of the surrounding normal tissue as possible. PBT is a newer technology that is designed to further reduce the amount of radiation that affects the surrounding normal tissue. However, this is still being studied.

Study Treatment:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups:

* If you are in Group 1, you will receive IMRT.
* If you are in Group 2, you will receive PBT.

You will receive radiation therapy 1 time each day, 5 days a week (Monday through Friday) for up to 28 treatments.

Your doctor may think it is in your best interest to also receive chemotherapy while you are receiving radiation therapy. If this occurs, you will sign a separate consent form for these drugs with a full description of how they are given and the risks they may cause.

Study Visits:

Before you begin receiving radiation therapy, you will have a baseline visit. The following tests and procedures will be performed:

* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* Your performance status will be recorded.
* You will have a PET/CT or CT scan to check the status of the disease.
* You will have lung function tests
* You will complete the symptom and quality of life questionnaires.
* Your esophagus will be examined using an endoscope. If the doctor thinks it is needed, you will have a biopsy to check the status of the disease.

You will then have a study visit every week while you are receiving radiation therapy. The following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status, weight, and vital signs will be recorded.
* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* You will complete the symptom and quality of life questionnaires.

Length of Study:

You will receive radiation therapy for up to 28 treatments (about 5½ weeks). You will no longer be able to receive radiation therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the follow-up visits.

Follow-Up:

After you stop receiving radiation therapy, there will be a 4-6 week break. During this time, you will contacted 2 times each week to complete the symptom and quality of life questionnaires. You will receive a call from an automated calling service or from the study staff at a scheduled time of your choosing. You will continue to be followed routinely during treatment and for follow-up visits and tests.

About 4-6 weeks after you stop receiving radiation therapy, the following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status, weight, and vital signs will be recorded.
* You will have a PET/CT scan to check the status of the disease.
* You will have lung function tests.
* Blood (about 1-2 tablespoons) will be drawn for routine tests.
* You will complete the symptom and quality of life questionnaires.
* Your esophagus will be examined using an endoscope. If the doctor thinks it is needed, you will have a biopsy to check the status of the disease.

If your doctor thinks it is in your best interest after you have completed radiation therapy, you will have surgery to remove the tumor. You will sign a separate consent form that describes the procedure and its risks. As part of this study, the study doctor will check you for side effects and discomfort after the surgery.

Every 3-4 months for 2 years, and then every 4-6 months for the next 3 years, you will have follow-up visits. The following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* Your performance status, weight, and vital signs will be recorded.
* You will have either a CT or a PET/CT scan to check the status of the disease.
* You will complete the symptom and quality of life questionnaires. (If the disease gets worse, these questionnaires will no longer be completed.)

Additionally, the following tests and procedures will be performed at follow-up visits only when the doctor thinks they are needed:

* Blood (about 1-2 tablespoons) may be drawn for routine tests.
* You may have lung function tests.
* Your esophagus will be examined using an endoscope. If the doctor thinks it is needed, you will have a biopsy to check the status of the disease.

You may be contacted by the study staff to ask about your health, even if you choose not to return to MD Anderson for follow-up visits after completing treatment for esophageal cancer.

This is an investigational study. IMRT and PBT are delivered using FDA-approved and commercially available methods. It is investigational to compare IMRT to PBT.

Up to 180 patients will take part in this study. All will be enrolled at MD Anderson.

Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiation Therapy (IMRT) Trial

Phase IIB Randomized Trial of Proton Beam Therapy Versus Intensity-Modulated Radiation Therapy for the Treatment of Esophageal Cancer

Defined from the time of enrollment to the date of death or any recurrence. The progression-free survival (PFS) time distribution will be estimated in each treatment arm using the Kaplan-Meier method.

TTB defined from the time of randomization to 12 months after randomization. Total toxicity burden (TTB) is computed as a composite score from serious adverse events (SAEs) and, among patients who undergo surgery, postoperative complications (POCs).

Massachusetts General Hospital

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Docetaxel

Fluorouracil

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Docetaxel 20 mg/m2 given by vein (IV) once a week up to 5 1/2 weeks. Dexamethasone 10 mg IV 30 minutes prior to weekly Docetaxel. 5-FU 300 mg/m2 IV, continuously for 96 hours 5 days a week for about 5 1/2 weeks. Radiation 50.4 Gy (1.8G/Fx/day) for about 5 1/2 weeks. Surgery to remove part of esophagus and nearby lymph nodes, approximately 8 to 10 weeks after completing chemoradiation.

20 mg/m2 given by vein (IV) over 1 hour once a week for up to 5 1/2 weeks.

300 mg/m2 given by vein, continuously for 96 hours a week for about 5 1/2 weeks.

5-FU

50.4 Gy (1.8G/Fx/day) for about 5 1/2 weeks, Monday through Friday.

Radiotherapy

Surgery to remove part of esophagus and nearby lymph nodes, approximately 8 to 10 weeks after completing chemoradiation.

Esophagectomy

10 mg IV 30 minutes prior to weekly Docetaxel.

Steven H. Lin, MD, PHD

The goal of this clinical research study is to learn if giving chemotherapy and radiation therapy before surgery for early-stage esophageal cancer can help to control the disease and if so, for how long. The safety of this treatment will also be studied.

The Study Treatment:

5-fluorouracil and docetaxel are designed to stop the growth of cancer cells, which may cause the cells to die. Docetaxel may also damage blood vessels in tumor tissue.

The radiation therapy in this study will be either intensity modulated radiation therapy (IMRT), which is a form of photon-based radiation therapy, or proton beam therapy (PBT). This will be up to your doctor. Both IMRT and PBT are designed to give radiation to the tumor area and limiting radiation exposure to nearby organs such as the lungs, heart, and spinal cord.

The surgery in this study removes part of the esophagus and nearby lymph nodes. The type of surgery will be the doctor's decision based on the location of the tumor in the esophagus. It will either be laparoscopic surgery (a minimally invasive procedure through small holes made in the abdomen) or open surgery (through the chest wall).

Study Treatment Administration:

If you are found to be eligible to take part in this study, you will receive radiation therapy and chemotherapy on the following schedule for up to 5 1/2 weeks. If there are holidays on the scheduled treatment days, the schedule may be slightly different and the study staff will discuss this with you.

* Radiation therapy will be given Monday through Friday. This will take about 30 minutes, including about 10-15 minutes for the radiation treatment.
* 5-fluorouracil will be given by vein, continuously for about 96 hours a week (Monday through Friday).
* Docetaxel will be given by vein over about 1 hour, 1 time a week (on Mondays).

  5-fluorouracil will be given using a portable pump about the size of a personal CD player. You will need to carry this portable pump with you for about 96 hours each week.

Docetaxel will be given through a central venous catheter. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. The catheter will be removed at the end of Week 5.

Before every dose of docetaxel, you will receive dexamethasone to lower the risk of side effects. Dexamethasone will be given by vein over a few seconds.

Your doctor will let you know if and when you are eligible to have surgery. In this study, the surgery must be performed within 8-10 weeks after you finish chemotherapy and radiation therapy. You will be asked to sign a separate consent form that describes the surgery and anesthesia (numbing medicine) and their risks in more detail. The screening tests that will help your doctor decide if you are eligible to have surgery include the scans and endoscopy described below (4-6 weeks after radiation and chemotherapy).

You will no longer be able to receive radiation and chemotherapy if the disease gets worse or intolerable side effects occur. You will not be able to have surgery if the doctor decides surgery is not in your best interest (for example, if the disease or your general health gets worse).

Study Visits:

During Study Therapy:

Blood (about 3 tablespoons) will be drawn for routine tests during Week 3 of radiation and chemotherapy.

Follow-Up:

At 4-6 weeks after your last dose of radiation and chemotherapy, the following tests and procedures will be performed:

* You will have a CT scan of the chest and a whole-body PET/CT scan to check the status of the disease.
* You may have an endoscopy of your esophagus with 1 or more biopsies of the tumor to check the status of the disease. The number of biopsies you have will be the doctor's decision at the time of the procedure, based on the status and location of the disease.
* Blood (about 3 tablespoons) will be drawn for routine tests.
* You will fill out 3 quality-of-life questionnaires. This should take about 10-15 minutes.

About 4 weeks after surgery, you will fill out 3 quality-of-life questionnaires. You will then fill out 2 quality-of-life questionnaires at 6 of your routine follow-up visits after surgery.

Every 3-6 months in the first 3 years after your last dose of radiation and chemotherapy, then every 6 months in the next 2 years, and every year after that from then on, the following tests and procedures will be performed:

* You will have a CT scan of the chest or a whole-body PET/CT scan to check the status of the disease.
* You will have an endoscopy of your esophagus to check the status of the disease during every follow-up visit in Year 1. After that, you will have an endoscopy of your esophagus at follow-up visits anytime the doctor decides it is needed. You will have 1 or more tumor biopsies at these follow-up visits if the doctor decides they are needed, based on the status and location of the disease. This will be decided at the time of the endoscopy.

Biomarker Testing:

If leftover tumor tissue is available from before you joined the study, the leftover tissue will be used for genetic biomarker testing. If you do not have leftover tumor tissue available from before you joined the study, leftover tissue from study procedures will be used for genetic biomarker testing.

This is an investigational study. Docetaxel and 5-fluorouracil are FDA approved and commercially available to treat esophageal cancer. However, it is investigational to give these drugs to patients with early-stage esophageal cancer.

It is investigational to give the combination of chemotherapy, radiation therapy, and surgery to patients with early-stage esophageal cancer.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Trimodality Management of T1b Esophageal Cancers

Phase IIB Study of Trimodality Management of Clinical T1bN0M0 Cancers of the Esophagus

The primary endpoint for this protocol is to assess the efficacy (pathologic complete response) and safety of Trimodality management (chemoradiotherapy followed by esophagectomy) in patients with clinically staged T1bN0M0 cancer of the esophagus or gastroesophageal junction. This is a single-arm phase IIB trial of chemo-radiation followed by surgery for patients with early stage grade T1b esophageal cancer. The rates of pathologic CR will be tabulated and their possible relationships to baseline covariates assessed by logistic regression. Unadjusted progression free survival time will be estimated by the method of Kaplan and Meier and its possible relationship to baseline covariates assessed by survival regression modeling.

Disease-free survival (DFS) defined as the time to disease progression or death. DFS calculated from the time of surgery to disease progression or death. Followed for disease recurrence every 3-6 months in the first 3 years after last dose of radiation and chemotherapy, then every 6 months in the next 2 years, then every year.

Toxicity was documented according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.0 during the 10-week period beginning at the start of chemo-radiation and ending at the time of surgery, and post-surgery mortality (PostDeath), defined as death due to any cause during the 30-day period following surgery.

Docetaxel + 5-FU + Radiation + Surgery

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

KPS≥ 80

KPS≥ 70

The Karnofsky Performance Status scores range from 0 to 100. The higher KPS scores, the better treatment outcome. KPS 80 Normal activity with effort; some signs or symptoms of disease. KPS 70 Cares for self; unable to carry on normal activity or to do active work.

Karnofsky performance score (KPS)

Never

Prior

Current

Smoking

Cardioesophageal Junction (GEJ)

Lower (distal) esophgus & GEJ

Tumor Location

Tumor Histology- Adenocarcinoma

Moderate to Poorly Differentiation

3 out of 4 patients was were consented and treated under this protocol. 1 patients withdrew consent prior to protocol treatment.

There are no statistical data analysis results available due to the protocol terminated early due to low rate of accrual, changes in treatment paradigm (patients are going for local excision for T1b esophageal cancer). We incorporated the analysis of those patient to the paper of a retrospective cohort, since the 4 patients themselves were not reportable.

Steven H. Lin, Associate Professor, Radiation Oncology Department

Pathologic Complete Response (PCR) Rate

There are no statistical data analysis results available because this protocol termination early due to low rate of accrual, changes in treatment paradigm (patients are going for local excision for T1b esophageal cancer).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiation Therapy (IMRT) Trial	NCT01512589	Esophageal Canc...	Proton Beam The... Intensity Modul... Questionnaires	18 Years -	M.D. Anderson Cancer Center
Trimodality Management of T1b Esophageal Cancers	NCT01217060	Esophageal Canc...	Docetaxel 5-FU Radiotherapy Esophagectomy Dexamethasone	18 Years -	M.D. Anderson Cancer Center
Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiation Therapy (IMRT) Trial	NCT01512589	Esophageal Canc...	Proton Beam The... Intensity Modul... Questionnaires	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for thoracic esophagus