Esophageal Adenocarcinoma
Conditions
Keywords
Esophageal, Esophagus
Brief summary
The primary objective of this pilot study is to determine whether neoadjuvant capecitabine/oxaliplatin/cetuximab and external beam radiation therapy followed by surgical resection \[and then followed by post operative adjuvant capecitabine, oxaliplatin and cetuximab\] is feasible and tolerable.
Detailed description
It is clear that new approaches are needed to improve the therapeutic ratio in esophageal cancer. This study proposes to evaluate the novel combination of preoperative capecitabine, oxaliplatin, and cetuximab concurrently with radiation therapy. This will be followed by esophagectomy 6-9 weeks after the completion of chemoradiation. Followed by further adjuvant chemotherapy. It is hypothesized that our novel combination of neoadjuvant capecitabine, oxaliplatin, and cetuximab combined with thoracoabdominal radiation therapy will be feasible and result in acceptable toxicity.
Interventions
DRUGCapecitabine
Given 650 mg/m\^2 BID on days of ration therapy, 825 mg/m\^2 day 1-14, day 15-20 off x 4
DRUGOxaliplatin
Oxaliplatin 30 mg/m\^2, 130mg/m2 IV Q 21 days x 4
DRUGCetuximab
Initial Cetuximab 400 mg/m\^2 IV starting no earlier than 8 weeks and no later than 10 weeks after surgical resection
Sponsors
Bristol-Myers Squibb
Sanofi
University of Colorado, Denver
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
* signed informed consent * patients 18 years of age or older * biopsy proven, non-recurrent primary adenocarcinoma of the thoracic esophagus or gastro-esophageal junction, disease confined to esophagus and peri-esophageal soft tissue, tumors at the gastroesophageal junction must be limited to no greater than 2 cm into the gastric cardia * clinical stage T3, N0-1 or T1-2, N1 and M0 or M1a (celiac axis lymph nodes are allowed) * Karnofsky Performance Status of \>60% * forced expiratory volume at one second (FeV1) must be \>1.0 L * adequate bone marrow reserve equal to or absolute neutrophil count (ANC) \> 1500/mcl, total white blood cell count (WBC) \> 3000/mcl, platelets \>100,000/mcl and hemoglobin \> 10.0 g/dl (transfusion permitted) * adequate hepatic function of direct serum bilirubin \< 2 times the upper limit of normal, total bilirubin \< 1.5 times the upper limit normal, alanine transaminase (ALT), aspartate transaminase (AST) \< 2.5 times the upper limit normal, Alkaline phosphatase \< 2.5 times the upper limit normal * creatinine clearance \> 50 ml/min * female patients of childbearing potential must have a negative serum or urin pregnancy test within 7 days prior to starting therapy
Exclusion criteria
* no previous resection or attempted resection of an esophageal cancer * women who are pregnant or lactating * life expectancy \< 3 months * serious, uncontrolled concurrent infection(s) * prior fluoropyrimidine therapy * prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known Dihydro Pyrimidine Dehydrogenase Deficiency (DPD) deficiency * treatment for other carcinomas within 5 years, except cured non-melanoma skin and treated in-situ cervical cancer * history of or evidence of uncontrolled diabetes * surgical procedure within 6 months of study entry * participation in any investigational drug study within 4 weeks preceding the start of study treatment * prior therapy with andy agent that specifically targets the Epidermal Growth Factor Receptor (EGFR) pathway * prior severe infusion reaction to a monoclonal antibody * acute hepatitis or known HIV * clinically significant cardia disease * evidence of metastases * other serious uncontrolled medical conditions that the investigator feels might compromise study participation * major surgery within 4 weeks of the start of treatment without complete recovery * lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome * known, existing uncontrolled coagulopathy * unwillingness to give written informed consent * unwillingness to participate or inability to comply with the protocol for the duration of the study * neuropathy of grade 2 or greater
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Toxicity | Up to 4 weeks | The primary objective of this pilot study was to determine whether neoadjuvant capecitabine/oxaliplatin/cetuximab and external beam radiation therapy followed by surgical resection and then followed by post operative adjuvant capecitabine, oxaliplatin and cetuximab is feasible with acceptable toxicity profile. |
Countries
United States
Participant flow
Recruitment details
Between November 2006 and August 2008, 8 patients were enrolled in the study from the Radiation Oncology clinic.
Pre-assignment details
This was to be a pilot/feasibility trial with a maximum of 15 patients enrolled, with the intent to propose a phase II trial. The study stopped before enrolling 15 patients, therefore the phase II trial was not pursued.
Participants by arm
| Arm | Count |
|---|---|
| Capecitabine, Oxaliplatin, Cetuximab, and Radiation Therapy Patients enrolled on the trial received neoadjuvant combined capecitabine, oxaliplatin, cetuximab, and radiation therapy. This was followed by surgical resection and adjuvant capecitabine, oxaliplatin, and cetuximab | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated | 8 |
Baseline characteristics
| Characteristic | Capecitabine, Oxaliplatin, Cetuximab, and Radiation Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age Continuous | 64.0 years STANDARD_DEVIATION 10.28 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
Overall Toxicity
The primary objective of this pilot study was to determine whether neoadjuvant capecitabine/oxaliplatin/cetuximab and external beam radiation therapy followed by surgical resection and then followed by post operative adjuvant capecitabine, oxaliplatin and cetuximab is feasible with acceptable toxicity profile.
Time frame: Up to 4 weeks
Population: The study was terminated, study end points were not reached.