Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI RTOG-0436 RTOG-0436, NCT00655876

Special Category: CTSU trial

Objectives

Primary

1. 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

1. 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.
2. To evaluate adverse events in these patients.
3. To evaluate endoscopic complete response rates in these patients.
4. 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.
5. To evaluate the quality-adjusted survival of each treatment arm using EQ-5D if the primary endpoint supports the primary hypothesis.

Entry Criteria

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



• 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 tracheoesophageal fistulas or invasion into the trachea or major bronchi
  • T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo bronchoscopy to exclude fistula

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

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 ≤ 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, carcinoma in situ of the breast, oral cavity, or cervix, and 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

Expected Enrollment

Outcomes

Overall survival

Local control
Adverse events as assessed by NCI CTCAE v3.0
Endoscopic complete response rate
Health-related quality of life (FACT-E)
Quality-adjusted survival (using EQ-5D), if primary hypothesis is supported

Outline

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

• 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.



• 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.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Mohan Suntharalingam, MD, Protocol chair		Ph: 410-328-2331; 800-888-8823 Email: msuntha@umm.edu
David Ilson, MD, PhD, Protocol co-chair		Ph: 212-639-8306; 800-525-2225

U.S.A.
California
	Auburn
	Auburn Radiation Oncology
		Christopher Jones, MD	Ph:  916-888-1266
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Cameron Park
	Radiation Oncology Centers - Cameron Park
		Christopher Jones, MD	Ph:  916-622-9700
	Carmichael
	Mercy Cancer Center at Mercy San Juan Medical Center
		Christopher Jones, MD	Ph:  916-904-3440
	Sacramento
	Mercy General Hospital
		Christopher Jones, MD	Ph:  916-453-4453
	Radiological Associates of Sacramento Medical Group, Incorporated
		Christopher Jones, MD	Ph:  916-646-8300
	Vacaville
	Solano Radiation Oncology Center
		Christopher Jones, MD	Ph:  707-447-0400
Delaware
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
Iowa
	Des Moines
	John Stoddard Cancer Center at Iowa Methodist Medical Center
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Methodist Medical Center	Ph:  515-241-6727
Maryland
	Baltimore
	Greenebaum Cancer Center at University of Maryland Medical Center
		Clinical Trials Office - Greenebaum Cancer Center at University of Maryladn Medical Center	Ph:  800-888-8823
New Hampshire
	Exeter
	Center for Cancer Care at Exeter Hospital
		Gary Proulx	Ph:  570-882-4048
New Jersey
	Long Branch
	Monmouth Medical Center
		Clinical Trials Office - Monmouth Medical Center	Ph:  732-923-7689
New York
	Glens Falls
	Charles R. Wood Cancer Center at Glens Falls Hospital
		Clinical Trials Office - Charles R. Wood Cancer Center at Glens Falls Hospital	Ph:  518-926-6700
Ohio
	Canton
	Mercy Cancer Center at Mercy Medical Center
		Mitchell Haut, MD	Ph:  330-453-9993
Oklahoma
	Tulsa
	Natalie Warren Bryant Cancer Center at St. Francis Hospital
		Charles Stewart	Ph:  918-494-2273
Pennsylvania
	Wynnewood
	Lankenau Cancer Center at Lankenau Hospital
		Paul Gilman, MD	Ph:  610-645-2000
	York
	York Cancer Center at Apple Hill Medical Center
		Amit Shah	Ph:  717-741-8180
South Dakota
	Rapid City
	Rapid City Regional Hospital
		Eric Eastmo, MD	Ph:  605-719-2360
Utah
	Murray
	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
		R. Jeffrey Lee, MD	Ph:  801-408-1146
	Salt Lake City
	Huntsman Cancer Institute at University of Utah
		Clinical Trials Office - Huntsman Cancer Institute at University of Utah	Ph:  801-581-4477
			Email: clinical.trials@hci.utah.edu
Washington
	Yakima
	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
		Clinical Trails Office - North Star Lodge Cancer Center	Ph:  509-574-3422

Registry Information
Official Title		A Phase III Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Patients with Esophageal Cancer who are Treated without Surgery
Trial Start Date		2008-06-30
Trial Completion Date		2011-09-01 (estimated)
Registered in ClinicalTrials.gov		NCT00655876
Date Submitted to PDQ		2008-03-31
Information Last Verified		2008-10-10
NCI Grant/Contract Number		CA21661