S0414 Cetuximab, Combo Chemo, and RT in Locally Advanced Esophageal Cancer
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|ClinicalTrials.gov Identifier: NCT00109850|
Recruitment Status : Terminated (Closed due to poor accrual)
First Posted : May 4, 2005
Results First Posted : August 23, 2012
Last Update Posted : November 18, 2015
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of esophageal cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab together with combination chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients with locally advanced esophageal cancer that cannot be removed by surgery.
|Condition or disease||Intervention/treatment||Phase|
|Esophageal Cancer||Biological: cetuximab Drug: cisplatin Drug: irinotecan hydrochloride Radiation: radiation therapy||Phase 2|
- Determine the 2-year overall survival of patients with previously untreated, clinically unresectable, locally advanced squamous cell carcinoma or adenocarcinoma of the esophagus treated with cetuximab, cisplatin, irinotecan, and thoracic radiotherapy.
- Determine the toxicity profile of this regimen in these patients.
- Determine the probability of objective response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen.
- Determine the time to progression in patients with measurable disease treated with this regimen.
- Correlate, preliminarily, gene expression (RNA) levels and germline polymorphisms of genes involved in DNA repair (e.g., ECRCC-1 and XRCC-1), drug metabolism (e.g., UGT1A1), and the epidermal growth factor receptor (EGFR) pathway (e.g., EGFR, interleukin-8, and vascular endothelial growth factor) with response, time to progression, overall survival, and toxicity in patients treated with this regimen. (This will not be completed as this study was closed due to poor accrual.)
OUTLINE: This is a multicenter study.
Patients receive cetuximab intravenous (IV) over 1-2 hours on days 1, 8, and 15. Patients also receive cisplatin IV and irinotecan IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of course 3, patients undergo thoracic radiotherapy once daily 5 days a week for 5-6 weeks (total of 28 treatments).
After completion of study treatment, patients are followed at 4 weeks and then every 3-6 months for up to 5 years after study entry.
PROJECTED ACCRUAL: A total of 75-100 patients (75 with adenocarcinoma and 25 with squamous cell carcinoma) will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Cetuximab Plus Cisplatin, Irinotecan and Thoracic Radiotherapy (TRT) for Locally Advanced (Non-Metastatic), Clinically Unresectable Esophageal Cancer: A Phase II Trial With Molecular Correlates|
|Study Start Date :||May 2005|
|Actual Primary Completion Date :||September 2009|
|Actual Study Completion Date :||May 2012|
Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
400mg/m^2 loading dose, intravenous (IV) over 120 min, day 1 of cycle 1 only. 250mg/m^2 maintenance dose, IV over 60 min, Days 8 & 15 of Cycle 1 and Days 1, 8, and 15 of subsequent cycles.
Other Name: ErbituxDrug: cisplatin
30mg/m^2, bolus intravenous (IV), on Days 1 & 8 of each cycle.
Other Name: PlatinolDrug: irinotecan hydrochloride
65mg/m^2, intravenous (IV) over 30 min, on Days 1 & 8 of each cycle.
Other Name: CPT-11Radiation: radiation therapy
The total dose to the prescription point will be 5,040 cGy given in 28 fractions. The patient will be treated with one fraction per day with all fields treated per day. 180 cGy will be delivered to the isocenter. The dose variation in the planning target volume (PTV) will be +7% and -5% of the prescription point dose.
- Overall Survival at 2 Years [ Time Frame: 0-2 years ]Measured from time of registration to date of death due to any cause, or last contact date
- Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events after every two cycles of chemotherapy. ]Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
- Objective Response (Confirmed and Unconfined, Complete and Partial) [ Time Frame: at week 16, then every 3 months until progression ]Complete response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. Partial response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration.
- Progression Free Survival [ Time Frame: 0 - 5 years ]Measured from date of registration to date of first observation of progression or symptomatic deterioration. Patients last known to be alive and progression-free are censored at date of last contact.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00109850
Show 132 Study Locations
|Study Chair:||Charles R. Thomas, MD||OHSU Knight Cancer Institute|
|Study Chair:||Charles D. Blanke, MD, FACP||OHSU Knight Cancer Institute|
|Study Chair:||James L. Abbruzzese, MD||M.D. Anderson Cancer Center|
|Study Chair:||Lisa Hammond, MD||The University of Texas Health Science Center at San Antonio|
|Study Chair:||Vivek Mehta, MD||Swedish Cancer Institute at Swedish Medical Center - First Hill Campus|