Official Title: “A Phase I/II Study of Docetaxel, 5-Fluorouracil and Oxaliplatin (D-FOX) in Patients With Untreated Locally Unresectable or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction”

Phase I Objectives

Primary:

1. The primary objective of this study is to determine the maximum tolerated dose (MTD) of Docetaxel combined with 5-Fluorouracil and Oxaliplatin (D-FOX) in patients with untreated, locally unresectable or metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ).

Secondary:

1. To determine the qualitative and quantitative toxicity and reversibility of toxicity of this combination.

Phase II Objectives

Primary:

1. To assess time to cancer progression to D-FOX treatment regimen.

Secondary:

1. To assess response rate to D-FOX treatment regimen.

2. To determine the qualitative and quantitative toxicity and reversibility of toxicity of this combination treatment regimen.

3. Determine overall survival.

4. Perform an exploratory investigation into the effect of D-FOX on phenotypic abnormalities in blood.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2010

Oxaliplatin and 5-FU are chemotherapy drugs that are commonly used to treat certain kinds of cancers. Oxaliplatin interferes with the DNA. 5-FU interferes with cell metabolism.

Docetaxel interferes with cell division.

Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will be asked questions about your medical history and have a complete physical exam. You will have around 1 tablespoon of blood drawn for routine tests. You will have your height and weight measured. You will have a chest x-ray and an electrocardiogram (ECG - a test that measures the electrical activity of the heart). You will also have a chest x-ray and a CT scan to check the size and location of the tumor.

Women who are able to have children must have a negative blood pregnancy test.

If you are found to be eligible to take part in this study, you will receive treatment with 5-FU as an infusion into a vein using a continuous 24- hour portable pump. This will start on Day 1 and will continue for 48 hours. You will need to carry this pump with you at all times for 48 hours. The pump is about the size of a Sony Walkman®. You will also receive oxaliplatin as an infusion into a vein over 2 hours on Day 1. Docetaxel will be given as an infusion over 60 minutes on Day 1. You will have 12 days to rest between chemotherapy treatments. These drugs may be given to you as an outpatient.

Treatment will be repeated on Day 15. Two 14-day treatment periods are called one cycle.

You will be asked to fill out side effect sheets throughout your participation in this research study. You will be asked questions regarding nausea, hair loss, fatigue, meals, and other questions regarding your daily activities. Before each dose of chemotherapy (every 14 days), you will have 1 teaspoon of blood drawn for routine tests.

If the cancer gets worse or you experience intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

You will be asked to come for a follow-up visit at M.D. Anderson about 2-3 months after treatment ends if possible. At this visit, you will have a full physical, about one tablespoon of blood drawn for routine tests, a chest x-ray, and CT or MRI scans.

This is an investigational study. Oxaliplatin is approved for treatment of colon and rectal cancer but not approved in the US for use in the treatment of gastric cancer. Docetaxel and 5-FU are commonly used drugs for gastric cancer and are commercially available. The combination of these 3 drugs (docetaxel + oxaliplatin + 5-FU) is investigational. A total of up to 106 patients will take part in this study. All will be enrolled at M.D.

Anderson.

Intervention(s) in this Clinical Trial

• Drug: 5-Fluorouracil
  • 2.2 Gm/m^2 IV over 48 hours on Day 1.
• Drug: Docetaxel
  • 20 mg/m^2 IV over 60 minutes
• Drug: Oxaliplatin
  • 85 mg/m^2 IV over 120 minutes on Day 1.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • 5-Fluorouracil + Docetaxel + Oxaliplatin

Primary Measures

• To find out if a combination of docetaxel, 5-FU, and oxaliplatin can shrink or slow the growth of cancer of the stomach or the junction between the stomach and the esophagus.
  • Time Frame: 6 Years
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Histologically documented adenocarcinoma of the stomach or GEJ.
• 2. Age >18 years;
• 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1;
• 4. Chemotherapy: No prior chemotherapy is permitted for metastatic disease. Use of prior chemotherapy in the adjuvant and/or neo-adjuvant setting or as part of a radiosensitization is permitted, provided that the minimum time from completion of such treatment to study entry is at least 12 months;
• 5. Radiation: Patients may have had prior radiation therapy that has not exceeded 25% of bone marrow reserve provided that they have recovered from the acute, toxic effects of radiotherapy prior to registration. A minimum of 14 days must have elapsed since the end of radiotherapy.
• 6. Previous Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration. Minimum of 14 days must have elapsed between a major surgery and start of chemotherapy.
• 7. At least one target lesion >20 mm (or >10 mm on spiral CT-scan). If indicator lesions are in a previously irradiated field, only a clear disease progression of the irradiated lesion or a new lesion in the previously irradiated field will be accepted
• 8. Adequate baseline bone marrow, hepatic and renal function, defined as follows:
• Neutrophils >1.5 x 10*9/L and platelets >100 x 10*9/L; Bilirubin <1.5 x upper limit of the normal range (ULN); AST and/or ALT <2.5 x ULN; Serum creatinine <1.5 x ULN;
• 9. Patients must give written informed consent to participate in the study.
• 10. Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of child-bearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to registration.

Exclusion Criteria:

• 1. Concurrent anticancer therapy
• 2. Pregnant or lactating women
• 3. History of other prior malignancy except for adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer or malignancy from which the patient has been disease-free for 5 years;
• 4. Brain metastases
• 5. Patients with active or uncontrolled infections or with serious illnesses or medical conditions, including patients with a history of chronic alcohol abuse, hepatitis, HIV and/or cirrhosis
• 6. History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent.
• 7. Known hypersensitivity to any of the drugs.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Jaffer Ajani, MD Principal Investigator U.T.M.D. Anderson Cancer Center  

Overall Contact: Jaffer Ajani, MD 713-792-2828 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00526110

Study ID Number: 2004-0290

ClinicalTrials.gov Identifier: NCT00526110

Health Authority: United States: Food and Drug Administration

UT MD Anderson Cancer Center