Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00655876
First received: April 9, 2008
Last updated: March 28, 2014
Last verified: March 2014

April 9, 2008
March 28, 2014
June 2008
August 2018   (final data collection date for primary outcome measure)
Overall survival (failure: death due to any cause) [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00655876 on ClinicalTrials.gov Archive Site
  • Local control (failure: residual cancer on post-treatment endoscopic biopsy or recurrent primary disease as defined in protocol) [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Endoscopic complete response rate [ Designated as safety issue: No ]
  • Health-related quality of life (FACT-E) [ Designated as safety issue: No ]
  • Quality-adjusted survival (using EQ-5D), if primary hypothesis is supported [ Designated as safety issue: No ]
  • Tissue handling/storage for future studies [ Designated as safety issue: No ]
  • Local control [ Designated as safety issue: No ]
  • Adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Endoscopic complete response rate [ Designated as safety issue: No ]
  • Health-related quality of life (FACT-E) [ Designated as safety issue: No ]
  • Quality-adjusted survival (using EQ-5D), if primary hypothesis is supported [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer
A Phase III Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Patients With Esophageal Cancer Who Are Treated Without Surgery

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, 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. 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 stop the growth of esophageal cancer by blocking blood flow to the tumor. It is not yet known whether giving paclitaxel and cisplatin together with radiation therapy is more effective with or without cetuximab in treating esophageal cancer.

PURPOSE: This randomized phase III trial is comparing how well giving paclitaxel and cisplatin together with radiation therapy works with or without cetuximab in treating patients with locally advanced esophageal cancer.

OBJECTIVES:

Primary

  • To evaluate whether the addition of cetuximab to chemotherapy comprising paclitaxel, cisplatin, and radiotherapy improves overall survival compared with paclitaxel, cisplatin, and radiotherapy alone in patients with esophageal cancer treated without surgery.

Secondary

  • To evaluate whether the addition of cetuximab to paclitaxel, cisplatin, and radiotherapy improves local control by increasing the clinical complete response and decreasing local recurrence in these patients.
  • To evaluate adverse events in these patients.
  • To evaluate endoscopic complete response rates in these patients.
  • To evaluate if the addition of cetuximab to paclitaxel, cisplatin, and radiotherapy improves the Esophageal Cancer Subscale score of the FACT-E quality of life tool.
  • To evaluate the quality-adjusted survival of each treatment arm using EQ-5D if the primary endpoint supports the primary hypothesis.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (adenocarcinoma* vs squamous), cancer lesion size (< 5 cm vs ≥ 5 cm), and disease status of celiac nodes (present vs absent). Patients are randomized to 1 of 2 treatment arms.

NOTE: * The adenocarcinoma stratum is closed as of 5/3/2012.

  • Arm I: Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiotherapy once daily, 5 days a week, for 5½ weeks for a total dose of 50.4Gy.
  • Arm II: Patients receive paclitaxel and cisplatin as in arm I. Patients also undergo radiotherapy as in arm I.

Patients undergo endoscopy 6 to 8 weeks after completion of chemoradiotherapy. Quality of life is assessed at baseline, within 1 week of post-treatment endoscopy, and at 1 and 2 years from beginning of study treatment.

After completion of study treatment, patients are followed periodically.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Esophageal Cancer
  • Biological: cetuximab
    Given IV
  • Drug: cisplatin
    Given IV
  • Drug: paclitaxel
    Given IV
  • Radiation: radiation therapy
    Given 5 days a week for 5½ weeks
  • Experimental: Arm I
    Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiotherapy once daily, 5 days a week, for 5½ weeks.
    Interventions:
    • Biological: cetuximab
    • Drug: cisplatin
    • Drug: paclitaxel
    • Radiation: radiation therapy
  • Active Comparator: Arm II
    Patients receive paclitaxel and cisplatin as in arm I. Patients also undergo radiotherapy as in arm I.
    Interventions:
    • Drug: cisplatin
    • Drug: paclitaxel
    • 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.
 
Active, not recruiting
420
Not Provided
August 2018   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary squamous cell or adenocarcinoma* of the esophagus or gastroesophageal junction

    • Patients with involvement of the gastroesophageal junction with Siewert type I or II tumors (tumors arising from the distal esophagus and involving the esophagogastric junction or tumors starting at the esophagogastric junction and involving the cardia) are eligible
    • Patients with cervical esophageal carcinoma are eligible
    • Patients with celiac, perigastric, mediastinal, or supraclavicular adenopathy are eligible NOTE: * The adenocarcinoma stratum is closed as of 5/3/2012.
  • Stage T1, N1, M0; T2-4, Any N, M0; or Any T, Any N, M1a disease based on history/physical examination, endoscopy with biopsy, AND PET/PET-CT scan or chest/abdominal CT scan within 6 weeks prior to registration
  • Disease must be encompassed in a radiotherapy field
  • No evidence of tracheoesophageal fistulas or invasion into the trachea or major bronchi

    • Patients with T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo bronchoscopy to exclude fistula

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • ANC ≥ 1,500/mm³
  • Platelets ≥ 100,000 cells/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL allowed)
  • Creatinine ≤ 1.5 mg/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 3 times ULN
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Total intake (oral/enteral) must be ≥ 1,500 kCal/day
  • No prior invasive malignancy except nonmelanomatous skin cancer (e.g., carcinoma in situ of the breast, oral cavity, or cervix) unless disease-free for ≥ 2 years
  • No prior allergic reaction to the study drugs
  • No prior severe infusion reaction to a monoclonal antibody
  • No severe, active comorbidity, including any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 3 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
    • Acquired immune deficiency syndrome based upon current CDC definition

      • HIV testing is not required for entry into this study

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for esophageal cancer (prior chemotherapy for another cancer allowed)
  • No prior therapy that specifically and directly targets the EGFR pathway
  • No prior platinum-based and/or paclitaxel-based therapy
  • No prior radiotherapy that would result in overlap of planned study radiotherapy fields
  • No concurrent investigational agent
  • No concurrent cytotoxic agent
  • No other concurrent radiotherapy
Both
18 Years to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00655876
RTOG 0436, CDR0000538085
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Mohan Suntharalingam, MD University of Maryland Greenebaum Cancer Center
Study Chair: David H. Ilson, MD, PhD Memorial Sloan-Kettering Cancer Center
Radiation Therapy Oncology Group
March 2014

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