Clinical trial NCT01217060: Trimodality Management of T1b Esophageal Cancers
Official title: Phase IIB Study of Trimodality Management of Clinical T1bN0M0 Cancers of the Esophagus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Esophageal Cancer
Keywords: Adenocarcinoma
Squamous cell carcinoma
Thoracic esophagus
Gastroesophageal junction
Chemoradiotherapy
Esophagectomy
5-Fluorouracil
Docetaxel
Radiation
Radiotherapy
XRT
IMRT
Taxotere
Adrucil
Efudex
Dexamethasone
Decadron
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2010-10-08
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Histologically documented adenocarcinoma or squamous cell carcinoma of the thoracic esophagus or gastroesophageal junction that are staged as T1b using endoscopic ultrasound (EUS) or from a large biopsy (either criteria # 1 or #2 can be met for eligibility).
2. Patients who undergo a diagnostic Endoscopic Mucosal Resection (EMR) and have a diagnosis of T1b stage established.
3. Performance score Karnofsky Performance Scale (KPS) 80-100.
4. Patients should be surgical candidates for esophagectomy and should have no contraindications for chemotherapy or radiation.
5. Negative pregnancy test for women of child bearing potential. They must agree to adequate contraception.
6. Complete blood count (CBC) and complete metabolic panel (chemo-14: Glucose, Calcium, Albumin, Total Protein, Sodium, Potassium, CO2, Chloride, Blood Urea Nitrogen (BUN), Creatinine, Alkaline Phosphatase, ALT (SGPT), AST (SGOT), and Bilirubin) to assess adequate hematologic, renal and hepatic functioning will be obtained. The values are as follows: Adequate hematologic (White Blood Count (WBC) \>2,500/uL, platelets \> 75,000/uL), renal (creatinine clearance \> 50 mL/min), and liver function (bilirubin \<=1.5 fold the upper limit of normal and liver enzymes \< 3 fold the upper limit of normal).
7. Based on the risk factors and propensity of lymph node metastasis (LNM) and poorer survivals seen in retrospective studies as discussed in the introduction, only patients with any one (1) of high risk features such as LVI, tumors \>1.2 cm, and high grade will be enrolled (Grade is the pathologic term defining the degree of differentiation. Grade 1 is well differentiated, Grade 2 is moderately differentiated, and Grade 3 is poorly differentiated).

Exclusion Criteria:

1. Prior radiation to the chest
2. Previous or concomitant cancers other than 1) curatively treated carcinoma in situ of cervix, basal cell of the skin, curative treatment for transitional cell carcinoma of the bladder, and early stage cancers at another non-overlapping site that was treated more than 3 years ago for cure.
3. Pregnant or breast-feeding females
4. Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal or hematologic disease but not limited to: a) active uncontrolled infection b) Symptomatic congestive heart failure, unstable angina, or cardiac dysrrhythmia not controlled by pacer device c) no myocardial infarction within 3 months of registration
5. Known hypersensitivity to docetaxel, 5-fluorouracil, polysorbate-80, or any component of the formulation

Primary outcomes:
measure: Pathologic Complete Response (PCR) Rate
timeFrame: Pathologic Complete Response (PCR) will repeat EGD with biopsy to assess for clinical response to therapy after chemoradiation four to six weeks.
Secondary outcomes:
measure: Disease-free Survival (DFS) Time
timeFrame: Time to disease progression or death, up to 6 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Steven H. Lin, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: