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
  Purpose

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 Intervention Phase
Esophageal Cancer
Biological: cetuximab
Drug: cisplatin
Drug: irinotecan hydrochloride
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 22
Study Start Date: May 2005
Study Completion Date: May 2012
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00109850

  Show 132 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
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
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00109850     History of Changes
Other Study ID Numbers: CDR0000426442, S0414, U10CA032102
Study First Received: May 3, 2005
Results First Received: June 14, 2012
Last Updated: July 20, 2012
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage III esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Irinotecan
Cetuximab
Cisplatin
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014