Gastrointestinal Diseases
Conditions
Keywords
Gastrointestinal Diseases, Adenocarcinoma of the Stomach, Gastroesophageal Junction Cancer, Cancer of the Stomach, 5-Fluorouracil, 5-FU, Adrucil, Efudex, Docetaxel, Oxaliplatin, Eloxatin, Taxotere, Esophagus
Brief summary
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.
Detailed description
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 computed tomography (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 magnetic resonance imaging (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.
Interventions
DRUG5-Fluorouracil
2.2 Gm/m\^2 IV over 48 hours on Day 1.
DRUGDocetaxel
20 mg/m\^2 IV over 60 minutes
DRUGOxaliplatin
85 mg/m\^2 IV over 120 minutes on Day 1.
Sponsors
Sanofi-Synthelabo
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically documented adenocarcinoma of the stomach or Gastroesophageal Junction (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 \* 10\*9/L and platelets \>100 \* 10\*9/L; Bilirubin \<1.5 \* upper limit of the normal range (ULN); aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) \<2.5 \* ULN; Serum creatinine \<1.5 \* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 28 days | MTD is the highest dose at which 1 or fewer dose limiting toxicities (DLT's) are observed in 6 patients. DLT defined as any non-hematologic grade III/IV or neutropenia-associated (infection or fever treated in the hospital) toxicity attributable to this therapy. Response evaluated after two 14-day treatments of Docetaxel, 5-Fluorouracil and Oxaliplatin (One cycle = 28 days). |
| Progression Free Survival | Assessed from baseline to 30 months | Progression Free Survival (PFS) defined as the time from the first study drug administration until the first day of radiological and/or symptomatic disease progression is documented, or the start of further anticancer therapy or death from any cause, whichever occurs first. Kaplan-Meier curve was used to estimate PFS. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | Up to 30 months | Overall survival was defined as the time from the start of treatment until death or last follow-up. Kaplan-Meier curve was used to estimate overall survival. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: September 8, 2004 to August 5, 2009. All recruitment was done at The University of Texas (UT) MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Phase I Phase I: Starting dose of 20mg/m\^2 IV Docetaxel over 60 minutes. Dose escalation of Docetaxel in 2.5 mg/m\^2 increments until the maximum tolerated dose is determined. 5-Fluorouracil by continuous infusion pump at a dose of 2.2 g/m\^2 over 48 hours on Day 1. Oxaliplatin 85 mg/m\^2 IV over 120 minutes on Day 1. Treatment was repeated every 14 days (one cycle = 28 days or two 14-day treatments). | 53 |
| Phase II Phase II: Docetaxel 50 mg/m\^2 IV over 60 minutes. 5-Fluorouracil by continuous infusion pump at a dose of 2.2 g/m\^2 over 48 hours on Day 1. Oxaliplatin 85 mg/m\^2 IV over 120 minutes on Day 1. Treatment was repeated every 14 days (one cycle = 28 days or two 14-day treatments). | 45 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 9 |
| Overall Study | Disease Progression | 0 | 19 |
| Overall Study | Maximal Response | 0 | 6 |
| Overall Study | Poor Tolerance | 0 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Phase I | Phase II | Total |
|---|---|---|---|
| Age, Continuous | 55 years | 59 years | 57 years |
| Region of Enrollment United States | 53 participants | 45 participants | 98 participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 41 Participants | 31 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 53 / 53 | 9 / 45 |
| serious Total, serious adverse events | 33 / 53 | 13 / 45 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
MTD is the highest dose at which 1 or fewer dose limiting toxicities (DLT's) are observed in 6 patients. DLT defined as any non-hematologic grade III/IV or neutropenia-associated (infection or fever treated in the hospital) toxicity attributable to this therapy. Response evaluated after two 14-day treatments of Docetaxel, 5-Fluorouracil and Oxaliplatin (One cycle = 28 days).
Time frame: 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I | Maximum Tolerated Dose (MTD) | 50 mg/m^2 |
Primary
Progression Free Survival
Progression Free Survival (PFS) defined as the time from the first study drug administration until the first day of radiological and/or symptomatic disease progression is documented, or the start of further anticancer therapy or death from any cause, whichever occurs first. Kaplan-Meier curve was used to estimate PFS. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion.
Time frame: Assessed from baseline to 30 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I | Progression Free Survival | 6.5 months |
Secondary
Median Overall Survival
Overall survival was defined as the time from the start of treatment until death or last follow-up. Kaplan-Meier curve was used to estimate overall survival.
Time frame: Up to 30 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I | Median Overall Survival | 11.1 months |