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

Sponsor
Southwest Oncology Group (Other)
Overall Status
Terminated
CT.gov ID
NCT00109850
Collaborator
National Cancer Institute (NCI) (NIH)
22
132
1
84
0.2
0

Study Details

Study Description

Brief Summary

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
  • Biological: cetuximab
  • Drug: cisplatin
  • Drug: irinotecan hydrochloride
  • Radiation: radiation therapy
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (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
Study Start Date :
May 1, 2005
Actual Primary Completion Date :
Sep 1, 2009
Actual Study Completion Date :
May 1, 2012

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • Erbitux
  • Drug: cisplatin
    30mg/m^2, bolus intravenous (IV), on Days 1 & 8 of each cycle.
    Other Names:
  • Platinol
  • Drug: irinotecan hydrochloride
    65mg/m^2, intravenous (IV) over 30 min, on Days 1 & 8 of each cycle.
    Other Names:
  • 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
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Survival at 2 Years [0-2 years]

      Measured from time of registration to date of death due to any cause, or last contact date

    Secondary Outcome Measures

    1. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [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.

    2. Objective Response (Confirmed and Unconfined, Complete and Partial) [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.

    3. Progression Free Survival [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Mobile Infirmary Medical Center Mobile Alabama United States 36652-2144
    2 Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    3 Alta Bates Comprehensive Cancer Center Berkeley California United States 94704
    4 Providence Saint Joseph Medical Center - Burbank Burbank California United States 91505
    5 Peninsula Medical Center Burlingame California United States 94010
    6 Eden Medical Center Castro Valley California United States 94546
    7 Marin Cancer Institute at Marin General Hospital Greenbrae California United States 94904
    8 Sutter Health - Western Division Cancer Research Group Greenbrae California United States 94904
    9 Saint Rose Hospital Hayward California United States 94545
    10 USC/Norris Comprehensive Cancer Center and Hospital Los Angeles California United States 90089-9181
    11 Highland General Hospital Oakland California United States 94602
    12 Alta Bates Summit Medical Center - Summit Campus Oakland California United States 94609
    13 CCOP - Bay Area Tumor Institute Oakland California United States 94609
    14 Desert Regional Medical Center Comprehensive Cancer Center Palm Springs California United States 92262
    15 Valley Care Medical Center Pleasanton California United States 94588
    16 University of California Davis Cancer Center Sacramento California United States 95817
    17 California Pacific Medical Center - California Campus San Francisco California United States 94118
    18 Doctors Medical Center - San Pablo Campus San Pablo California United States 94806
    19 CCOP - Santa Rosa Memorial Hospital Sana Rosa California United States 95405
    20 Sutter Solano Medical Center Vallejo California United States 94589
    21 Poudre Valley Hospital Fort Collins Colorado United States 80524
    22 Watson Clinic, LLC Lakeland Florida United States 33804-5000
    23 Augusta Oncology Associates - Walton Way Augusta Georgia United States 30901
    24 Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center Savannah Georgia United States 31403-3089
    25 Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler Savannah Georgia United States 31405
    26 St. Luke's Mountain States Tumor Institute - Boise Boise Idaho United States 83712
    27 Regional Cancer Center at Memorial Medical Center Springfield Illinois United States 62781-0001
    28 St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove Indiana United States 46107
    29 Reid Hospital & Health Care Services, Incorporated Richmond Indiana United States 47374
    30 Cancer Center of Kansas, PA - Chanute Chanute Kansas United States 66720
    31 Cancer Center of Kansas, PA - Dodge City Dodge City Kansas United States 67801
    32 Cancer Center of Kansas, PA - El Dorado El Dorado Kansas United States 67042
    33 Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City Kansas United States 66160-7357
    34 Cancer Center of Kansas, PA - Kingman Kingman Kansas United States 67068
    35 Southwest Medical Center Liberal Kansas United States 67901
    36 Cancer Center of Kansas, PA - Newton Newton Kansas United States 67114
    37 Cancer Center of Kansas, PA - Parsons Parsons Kansas United States 67357
    38 Cancer Center of Kansas, PA - Pratt Pratt Kansas United States 67124
    39 Cancer Center of Kansas, PA - Salina Salina Kansas United States 67042
    40 Tammy Walker Cancer Center at Salina Regional Health Center Salina Kansas United States 67401
    41 Cancer Center of Kansas, PA - Wellington Wellington Kansas United States 67152
    42 Associates in Womens Health, PA - North Review Wichita Kansas United States 67203
    43 Cancer Center of Kansas, PA - Medical Arts Tower Wichita Kansas United States 67208
    44 Cancer Center of Kansas, PA - Wichita Wichita Kansas United States 67214
    45 CCOP - Wichita Wichita Kansas United States 67214
    46 Via Christi Cancer Center at Via Christi Regional Medical Center Wichita Kansas United States 67214
    47 Wesley Medical Center Wichita Kansas United States 67214
    48 Cancer Center of Kansas, PA - Winfield Winfield Kansas United States 67156
    49 Markey Cancer Center at University of Kentucky Chandler Medical Center Lexington Kentucky United States 40536-0293
    50 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109-0942
    51 Battle Creek Health System Cancer Care Center Battle Creek Michigan United States 49017
    52 Mecosta County Medical Center Big Rapids Michigan United States 49307
    53 Josephine Ford Cancer Center at Henry Ford Hospital Detroit Michigan United States 48202
    54 CCOP - Grand Rapids Grand Rapids Michigan United States 49503
    55 Lacks Cancer Center at Saint Mary's Health Care Grand Rapids Michigan United States 49503
    56 Spectrum Health Hospital - Butterworth Campus Grand Rapids Michigan United States 49503
    57 Metro Health Hospital Grand Rapids Michigan United States 49506
    58 Holland Community Hospital Holland Michigan United States 49423
    59 Hackley Hospital Muskegon Michigan United States 49442
    60 Munson Medical Center Traverse City Michigan United States 49684
    61 CCOP - Kansas City Kansas City Missouri United States 64131
    62 Saint Louis University Cancer Center Saint Louis Missouri United States 63110
    63 CCOP - Cancer Research for the Ozarks Springfield Missouri United States 65802
    64 St. John's Regional Health Center Springfield Missouri United States 65804
    65 Hulston Cancer Center at Cox Medical Center South Springfield Missouri United States 65807
    66 CCOP - Montana Cancer Consortium Billings Montana United States 59101
    67 Hematology-Oncology Centers of the Northern Rockies - Billings Billings Montana United States 59101
    68 Northern Rockies Radiation Oncology Center Billings Montana United States 59101
    69 St. Vincent Healthcare Cancer Care Services Billings Montana United States 59101
    70 Billings Clinic - Downtown Billings Montana United States 59107-7000
    71 Bozeman Deaconess Cancer Center Bozeman Montana United States 59715
    72 St. James Healthcare Cancer Care Butte Montana United States 59701
    73 Great Falls Clinic - Main Facility Great Falls Montana United States 59405
    74 Great Falls Montana United States 59405
    75 St. Peter's Hospital Helena Montana United States 59601
    76 Glacier Oncology, PLLC Kalispell Montana United States 59901
    77 Kalispell Medical Oncology at KRMC Kalispell Montana United States 59901
    78 Kalispell Regional Medical Center Kalispell Montana United States 59901
    79 Community Medical Center Missoula Montana United States 59801
    80 Guardian Oncology and Center for Wellness Missoula Montana United States 59804
    81 Montana Cancer Specialists at Montana Cancer Center Missoula Montana United States 59807-7877
    82 Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula Montana United States 59807
    83 Good Samaritan Cancer Center at Good Samaritan Hospital Kearney Nebraska United States 68848-1990
    84 Interlakes Oncology/Hematology PC Rochester New York United States 14623
    85 James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York United States 14642
    86 Wayne Memorial Hospital, Incorporated Goldsboro North Carolina United States 27534
    87 McDowell Cancer Center at Akron General Medical Center Akron Ohio United States 44307
    88 Grandview Hospital Dayton Ohio United States 45405
    89 Good Samaritan Hospital Dayton Ohio United States 45406
    90 David L. Rike Cancer Center at Miami Valley Hospital Dayton Ohio United States 45409
    91 Samaritan North Cancer Care Center Dayton Ohio United States 45415
    92 Veterans Affairs Medical Center - Dayton Dayton Ohio United States 45428
    93 CCOP - Dayton Dayton Ohio United States 45429
    94 Blanchard Valley Medical Associates Findlay Ohio United States 45840
    95 Charles F. Kettering Memorial Hospital Kettering Ohio United States 45429
    96 Middletown Regional Hospital Middletown Ohio United States 45044
    97 UVMC Cancer Care Center at Upper Valley Medical Center Troy Ohio United States 45373-1300
    98 Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia Ohio United States 45385
    99 Legacy Mount Hood Medical Center Gresham Oregon United States 97030
    100 Providence Milwaukie Hospital Milwaukie Oregon United States 97222
    101 Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center Portland Oregon United States 97210
    102 Providence Cancer Center at Providence Portland Medical Center Portland Oregon United States 97213-2967
    103 CCOP - Columbia River Oncology Program Portland Oregon United States 97225
    104 Providence St. Vincent Medical Center Portland Oregon United States 97225
    105 Legacy Emanuel Hospital and Health Center & Children's Hospital Portland Oregon United States 97227
    106 Northwest Cancer Specialists at Rose Quarter Cancer Center Portland Oregon United States 97227
    107 Oregon Health & Science University Cancer Institute Portland Oregon United States 97239-3098
    108 Salem Hospital Regional Cancer Care Services Salem Oregon United States 97309-5014
    109 Legacy Meridian Park Hospital Tualatin Oregon United States 97062
    110 Roper St. Francis Cancer Center at Roper Hospital Charleston South Carolina United States 29401
    111 Hollings Cancer Center at Medical University of South Carolina Charleston South Carolina United States 29425
    112 CCOP - Greenville Greenville South Carolina United States 29615
    113 Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center Kingsport Tennessee United States 37662
    114 U.T. Cancer Institute at University of Tennessee Medical Center Knoxville Tennessee United States 37920-6999
    115 Danville Regional Medical Center Danville Virginia United States 24541
    116 Southwest Virginia Regional Cancer Center Norton Virginia United States 24273
    117 St. Joseph Cancer Center Bellingham Washington United States 98225
    118 Olympic Hematology and Oncology Bremerton Washington United States 98310
    119 Columbia Basin Hematology Kennewick Washington United States 99336
    120 Skagit Valley Hospital Cancer Care Center Mt. Vernon Washington United States 98273
    121 Fred Hutchinson Cancer Research Center Seattle Washington United States 98104
    122 Harborview Medical Center Seattle Washington United States 98104
    123 Minor and James Medical, PLLC Seattle Washington United States 98104
    124 Group Health Central Hospital Seattle Washington United States 98112
    125 Swedish Cancer Institute at Swedish Medical Center - First Hill Campus Seattle Washington United States 98122-4307
    126 Polyclinic First Hill Seattle Washington United States 98122
    127 University Cancer Center at University of Washington Medical Center Seattle Washington United States 98195-6043
    128 Cancer Care Northwest - Spokane South Spokane Washington United States 99202
    129 Southwest Washington Medical Center Cancer Center Vancouver Washington United States 98668
    130 Northwest Cancer Specialists at Vancouver Cancer Center Vancouver Washington United States 98684
    131 Wenatchee Valley Medical Center Wenatchee Washington United States 98801-2028
    132 Welch Cancer Center at Sheridan Memorial Hospital Sheridan Wyoming United States 82801

    Sponsors and Collaborators

    • Southwest Oncology Group
    • National Cancer Institute (NCI)

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00109850
    Other Study ID Numbers:
    • CDR0000426442
    • S0414
    • U10CA032102
    First Posted:
    May 4, 2005
    Last Update Posted:
    Nov 18, 2015
    Last Verified:
    Nov 1, 2015

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Treatment
    Arm/Group Description Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3
    Period Title: Overall Study
    STARTED 22
    Eligible 21
    Eligible and Began Protocol Therapy 21
    COMPLETED 18
    NOT COMPLETED 4

    Baseline Characteristics

    Arm/Group Title Treatment
    Arm/Group Description Cetuximab+Cisplatin+Irinotecan followed by radiation therapy (RT) in Cycle 3
    Overall Participants 21
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    61.4
    Sex: Female, Male (Count of Participants)
    Female
    6
    28.6%
    Male
    15
    71.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    20
    95.2%
    Unknown or Not Reported
    1
    4.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    2
    9.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    19%
    White
    15
    71.4%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival at 2 Years
    Description Measured from time of registration to date of death due to any cause, or last contact date
    Time Frame 0-2 years

    Outcome Measure Data

    Analysis Population Description
    All eligible patients who started treatment were included in the analysis.
    Arm/Group Title Cetuximab+Cisplatin+Irinotecan Followed by Radiation Therapy
    Arm/Group Description Patients received four 21-day cycles of cetuximab 400 mg/m^2 (day 1, cycle 1), cetuximab 250 mg/m^2 (day 8, 15, cycle 1, then days 1, 8 and 15 for subsequent cycles), cisplatin 30 mg/m^2 (days 1 and 8, all cycles), and irinotecan 65 mg/m^2 (days 1 and 8, all cycles). Thoracic Radiotherapy (TRT) was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, beginning on day 1 of cycle 3.
    Measure Participants 21
    Number (95% Confidence Interval) [percentage of participants]
    33.3
    158.6%
    2. Secondary Outcome
    Title Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
    Description 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.
    Time Frame Patients were assessed for adverse events after every two cycles of chemotherapy.

    Outcome Measure Data

    Analysis Population Description
    Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
    Arm/Group Title Cetuximab+Cisplatin+Irinotecan Followed by Radiation Therapy
    Arm/Group Description Patients received four 21-day cycles of cetuximab 400 mg/m^2 (day 1, cycle 1), cetuximab 250 mg/m^2 (day 8, 15, cycle 1, then days 1, 8 and 15 for subsequent cycles), cisplatin 30 mg/m^2 (days 1 and 8, all cycles), and irinotecan 65 mg/m^2 (days 1 and 8, all cycles). Thoracic Radiotherapy (TRT) was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, beginning on day 1 of cycle 3.
    Measure Participants 21
    Albumin, serum-low (hypoalbuminemia)
    1
    4.8%
    Anorexia
    4
    19%
    CNS cerebrovascular ischemia
    1
    4.8%
    Calcium, serum-low (hypocalcemia)
    1
    4.8%
    Creatinine
    1
    4.8%
    Death not associated w/CTCAE term - Sudden death
    1
    4.8%
    Dehydration
    4
    19%
    Dermatology/Skin-Other (Specify)
    1
    4.8%
    Diarrhea
    5
    23.8%
    Dysphagia (difficulty swallowing)
    3
    14.3%
    Esophagitis
    2
    9.5%
    Fatigue (asthenia, lethargy, malaise)
    5
    23.8%
    Febrile neutropenia
    1
    4.8%
    Glucose, serum-high (hyperglycemia)
    1
    4.8%
    Hemoglobin
    3
    14.3%
    Leukocytes (total WBC)
    9
    42.9%
    Lymphopenia
    4
    19%
    Magnesium, serum-low (hypomagnesemia)
    1
    4.8%
    Nausea
    4
    19%
    Necrosis, GI - Colon/cecum/appendix
    1
    4.8%
    Neuropathy: sensory
    1
    4.8%
    Neutrophils/granulocytes (ANC/AGC)
    6
    28.6%
    Pain - Abdomen NOS
    1
    4.8%
    Pain - Esophagus
    1
    4.8%
    Perforation, GI - Colon
    1
    4.8%
    Potassium, serum-low (hypokalemia)
    2
    9.5%
    Rash: acne/acneiform
    1
    4.8%
    Renal failure
    1
    4.8%
    Sodium, serum-low (hyponatremia)
    1
    4.8%
    Thrombosis/thrombus/embolism
    1
    4.8%
    Typhlitis (cecal inflammation)
    1
    4.8%
    Vomiting
    3
    14.3%
    Weight loss
    1
    4.8%
    3. Secondary Outcome
    Title Objective Response (Confirmed and Unconfined, Complete and Partial)
    Description 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.
    Time Frame at week 16, then every 3 months until progression

    Outcome Measure Data

    Analysis Population Description
    All eligible patients who started treatment and were evaluable for response were included in assessing response estimates.
    Arm/Group Title Cetuximab+Cisplatin+Irinotecan Followed by Radiation Therapy
    Arm/Group Description Patients received four 21-day cycles of cetuximab 400 mg/m^2 (day 1, cycle 1), cetuximab 250 mg/m^2 (day 8, 15, cycle 1, then days 1, 8 and 15 for subsequent cycles), cisplatin 30 mg/m^2 (days 1 and 8, all cycles), and irinotecan 65 mg/m^2 (days 1 and 8, all cycles). Thoracic Radiotherapy (TRT) was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, beginning on day 1 of cycle 3.
    Measure Participants 17
    Number (95% Confidence Interval) [percentage of participants]
    17.6
    83.8%
    4. Secondary Outcome
    Title Progression Free Survival
    Description 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.
    Time Frame 0 - 5 years

    Outcome Measure Data

    Analysis Population Description
    All eligible patients who started treatment were included in the analysis.
    Arm/Group Title Cetuximab+Cisplatin+Irinotecan Followed by Radiation Therapy
    Arm/Group Description Patients received four 21-day cycles of cetuximab 400 mg/m^2 (day 1, cycle 1), cetuximab 250 mg/m^2 (day 8, 15, cycle 1, then days 1, 8 and 15 for subsequent cycles), cisplatin 30 mg/m^2 (days 1 and 8, all cycles), and irinotecan 65 mg/m^2 (days 1 and 8, all cycles). Thoracic Radiotherapy (TRT) was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, beginning on day 1 of cycle 3.
    Measure Participants 21
    Median (95% Confidence Interval) [months]
    6.4

    Adverse Events

    Time Frame Patients were assessed for adverse events after every two cycles of chemotherapy.
    Adverse Event Reporting Description Only adverse events and serious adverse events that are possibly, probably or definitely related to study drug are reported.
    Arm/Group Title Cetuximab+Cisplatin+Irinotecan Followed by RT in Cycle 3
    Arm/Group Description Patients received four 21-day cycles of cetuximab 400 mg/m^2 (day 1, cycle 1), cetuximab 250 mg/m^2 (day 8, 15, cycle 1, then days 1, 8 and 15 for subsequent cycles), cisplatin 30 mg/m^2 (days 1 and 8, all cycles), and irinotecan 65 mg/m^2 (days 1 and 8, all cycles). Thoracic Radiotherapy (TRT) was administered at 1.8 Gy in 28 daily fractions to a total dose of 50.4 Gy, beginning on day 1 of cycle 3.
    All Cause Mortality
    Cetuximab+Cisplatin+Irinotecan Followed by RT in Cycle 3
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Cetuximab+Cisplatin+Irinotecan Followed by RT in Cycle 3
    Affected / at Risk (%) # Events
    Total 3/21 (14.3%)
    Gastrointestinal disorders
    Necrosis, GI - Colon/cecum/appendix 1/21 (4.8%)
    General disorders
    Death not associated with CTCAE term - Sudden death 1/21 (4.8%)
    Nervous system disorders
    CNS cerebrovascular ischemia 1/21 (4.8%)
    Other (Not Including Serious) Adverse Events
    Cetuximab+Cisplatin+Irinotecan Followed by RT in Cycle 3
    Affected / at Risk (%) # Events
    Total 21/21 (100%)
    Blood and lymphatic system disorders
    Hemoglobin 10/21 (47.6%)
    Gastrointestinal disorders
    Constipation 9/21 (42.9%)
    Diarrhea 15/21 (71.4%)
    Dysphagia (difficulty swallowing) 8/21 (38.1%)
    Esophagitis 4/21 (19%)
    Heartburn/dyspepsia 2/21 (9.5%)
    Mucositis/stomatitis (clinical exam) - Oral cavity 4/21 (19%)
    Mucositis/stomatitis (functional/symptomatic) - Oral cavity 3/21 (14.3%)
    Nausea 19/21 (90.5%)
    Pain - Abdomen NOS 2/21 (9.5%)
    Pain - Esophagus 4/21 (19%)
    Vomiting 10/21 (47.6%)
    General disorders
    Fatigue (asthenia, lethargy, malaise) 16/21 (76.2%)
    Injury, poisoning and procedural complications
    Rash: dermatitis associated with radiation - Chemoradiation 2/21 (9.5%)
    Investigations
    ALT, SGPT (serum glutamic pyruvic transaminase) 2/21 (9.5%)
    AST, SGOT (serum glutamic oxaloacetic transaminase) 2/21 (9.5%)
    Alkaline phosphatase 4/21 (19%)
    Leukocytes (total WBC) 14/21 (66.7%)
    Lymphopenia 4/21 (19%)
    Neutrophils/granulocytes (ANC/AGC) 14/21 (66.7%)
    Platelets 8/21 (38.1%)
    Weight loss 10/21 (47.6%)
    Metabolism and nutrition disorders
    Albumin, serum-low (hypoalbuminemia) 5/21 (23.8%)
    Anorexia 8/21 (38.1%)
    Calcium, serum-low (hypocalcemia) 6/21 (28.6%)
    Dehydration 4/21 (19%)
    Glucose, serum-high (hyperglycemia) 6/21 (28.6%)
    Magnesium, serum-low (hypomagnesemia) 8/21 (38.1%)
    Potassium, serum-low (hypokalemia) 5/21 (23.8%)
    Sodium, serum-low (hyponatremia) 6/21 (28.6%)
    Musculoskeletal and connective tissue disorders
    Pain - Muscle 2/21 (9.5%)
    Nervous system disorders
    Neuropathy: sensory 2/21 (9.5%)
    Taste alteration (dysgeusia) 4/21 (19%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/21 (9.5%)
    Skin and subcutaneous tissue disorders
    Dry skin 7/21 (33.3%)
    Hair loss/Alopecia (scalp or body) 2/21 (9.5%)
    Rash/desquamation 2/21 (9.5%)
    Rash: acne/acneiform 13/21 (61.9%)
    Vascular disorders
    Hypotension 2/21 (9.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Study Statistician
    Organization SWOG Statistical Center
    Phone 206-667-4623
    Email
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT00109850
    Other Study ID Numbers:
    • CDR0000426442
    • S0414
    • U10CA032102
    First Posted:
    May 4, 2005
    Last Update Posted:
    Nov 18, 2015
    Last Verified:
    Nov 1, 2015