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S0414 Cetuximab, Combo Chemo, and RT in Locally Advanced Esophageal Cancer

This study has been terminated.
(Closed due to poor accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00109850
First received: May 3, 2005
Last updated: July 20, 2012
Last verified: July 2012

May 3, 2005
July 20, 2012
May 2005
September 2009   (final data collection date for primary outcome measure)
Overall Survival at 2 Years [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
Measured from time of registration to date of death due to any cause, or last contact date
Not Provided
Complete list of historical versions of study NCT00109850 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
Not Provided
Not Provided
Not Provided
 
S0414 Cetuximab, Combo Chemo, and RT in Locally Advanced Esophageal Cancer
Cetuximab Plus Cisplatin, Irinotecan and Thoracic Radiotherapy (TRT) for Locally Advanced (Non-Metastatic), Clinically Unresectable Esophageal Cancer: A Phase II Trial With Molecular Correlates

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.

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Esophageal Cancer
  • Biological: cetuximab
    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: Erbitux
  • Drug: cisplatin
    30mg/m^2, bolus intravenous (IV), on Days 1 & 8 of each cycle.
    Other Name: Platinol
  • Drug: irinotecan hydrochloride
    65mg/m^2, intravenous (IV) over 30 min, on Days 1 & 8 of each cycle.
    Other Name: CPT-11
  • Radiation: 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.
    Other Names:
    • RT
    • TRT
Experimental: Treatment
Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
Interventions:
  • Biological: cetuximab
  • Drug: cisplatin
  • Drug: irinotecan hydrochloride
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
22
May 2012
September 2009   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (≥ 20 cm from the incisors*) or the gastroesophageal junction (confined to ≤ 2 cm into the gastric cardia)

    • Disease confined to the esophagus or peri-esophageal soft tissue
    • T4, M0 disease
    • Surgically unresectable disease by esophageal endoscopic ultrasonography OR medically unresectable disease

NOTE: *Patients with primary disease < 26 cm from the incisors must undergo bronchoscopy AND have negative cytology within the past 4 weeks

  • Measurable or non-measurable disease by x-ray, CT scan and/or MRI, or physical examination within the past 4 weeks (for measurable disease) or within the past 6 weeks (for non-measurable disease)
  • Tumor specimens available
  • No recurrent disease

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • White Blood Cell (WBC) count ≥ 3,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL

Hepatic

  • Albumin normal
  • Bilirubin normal
  • Alkaline phosphatase normal
  • Serum glutamic oxaloacetic transaminase (SGOT) or Serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times upper limit of normal

Renal

  • Creatinine clearance > 50 mL/min

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No prior severe reaction to monoclonal antibodies
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for esophageal cancer

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy for esophageal cancer
  • No concurrent intensity modulated radiotherapy
  • No concurrent cobalt-60

Surgery

  • No prior surgical resection or attempted surgical resection of esophageal cancer
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00109850
CDR0000426442, S0414, U10CA032102
Yes
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
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
Southwest Oncology Group
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP