Clinical trial NCT00757172: Panitumumab, Docetaxel, Cisplatin, Radiation Therapy, and Surgery in Treating Patients With Newly Diagnosed, Locally Advanced Esophageal Cancer or Cancer of the Gastroesophageal Junction
Official title: A Phase II Study of Neoadjuvant Therapy With Cisplatin, Docetaxel, Panitumumab Plus Radiation Therapy Followed by Surgery in Patients With Locally Advanced Adenocarcinoma of the Distal Esophagus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Gastroesophageal Junction
Esophageal Cancer
Keywords: adenocarcinoma of the esophagus
adenocarcinoma of the gastroesophageal junction
stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Amgen
First posted: 2008-09-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as panitumumab, 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. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to kill tumor cells or stop them from growing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with panitumumab and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving panitumumab together with docetaxel, cisplatin, radiation therapy, and surgery works in treating patients with newly diagnosed, locally advanced esophageal cancer or cancer of the gastroesophageal junction.

Detailed description: OBJECTIVES:

Primary

* To determine the pathologic complete response rate in patients with newly diagnosed, locally advanced adenocarcinoma of the distal esophagus or gastroesophageal junction treated with neoadjuvant panitumumab and combination chemoradiotherapy followed by surgery.

Secondary

* To determine the near-complete pathologic response rate in the primary tumor (≤ 10% residual viable cancer).
* To determine the overall survival and disease-free survival rates of these patients.
* To determine the safety profile of this regimen.

OUTLINE: Patients receive panitumumab IV over 1 hour, docetaxel IV over 1 hour, and cisplatin IV over 1-2 hours on day 1 in weeks 1, 3, 5, 7, and 9. Patients also undergo radiotherapy once daily 5 days a week beginning in week 5 and continuing for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 6-9 weeks after completion of chemoradiotherapy, patients with no evidence of metastatic disease undergo esophagectomy.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year OR every 6 months for 3 years.

Eligibility criteria: 1. ≥ 18 years old
2. ECOG/Zubrod Performance Status 0-1
3. Biopsy-proven resectable primary (nonrecurrent) adenocarcinoma of the distal esophagus or GE junction (Siewert Type I or II)

   * Siewert Type I: adenocarcinoma of the distal esophagus
   * Siewert Type II: adenocarcinoma of the esophago-gastric junction/real cardia
4. Pre-registration EUS, CT of chest and upper abdomen, and PET must support a clinical stage of T3N0M0, T2-3N1M0 or T2-3N0-1M1a (celiac adenopathy must be ≤ 2 cm by EUS). Clinically staged T1 tumors and T2N0M0 tumors are not eligible. N1 does not require biopsy/FNA. Note: Patients requiring a stent for nutrition must have staging examinations and scans completed before stent placement.
5. No definitive radiological evidence of distant metastases.
6. No pre-existing grade 2 or greater peripheral neuropathy (CTCAE v3) of any etiology.
7. Adequate bone marrow, hepatic and renal function prior to registration:

   * WBC ≥ 3,000/mm³
   * ANC ≥ 1,500/mm³
   * Platelet count ≥ 100,000/mm³
   * Hemoglobin ≥ 9.5 g/dL
   * Creatinine ≤ 1.5 mg/dL
   * Total bilirubin ≤ 3 mg/dL
   * AST (SGOT) ≤ 2.0 times upper limit of normal (ULN)
   * ALT (SGPT) ≤ 2.0 times ULN
   * Alkaline phosphatase ≤ 2.0 times ULN
   * Albumin ≥ 2.0 g/dL OR prealbumin ≥ 15 mg/dL
   * Magnesium ≥ lower limit of normal (LLN)
8. Patient must be evaluated before registration by medical oncologist, radiation oncologist and surgeon and deemed fit for protocol therapy and surgery.
9. No prior invasive malignancy, unless disease-free for ≥ 5 years prior to registration (Exceptions: non-melanoma skin cancer, in-situ cancers).
10. Non-pregnant and non-breast feeding. Female participants of child-bearing potential must have a negative urine or serum pregnancy test prior to registration. Perimenopausal participants must be amenorrheic ≥ 12 months to be considered not of childbearing potential. All patients of reproductive potential must agree to use an an effective method of birth-control while receiving study therapy and for six months after completion of therapy.
11. No prior chest or upper abdomen radiotherapy; prior therapy with cisplatin, docetaxel, panitumumab or other anti-EGFR therapy or prior esophageal or gastric surgery (Exception: prior surgery to treat reflux disease)
12. No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psyschiatric illness/social situations that would limit compliance with study requirements.
13. No history of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan
14. No history of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results.

Primary outcomes:
measure: Number of Participants With Pathologic Complete Response Following Surgery
timeFrame: Post surgery
Secondary outcomes:
measure: Number of Participants With Near-complete Response Rate (≤ 10% Residual Cancer in Primary Tumor Viable)
timeFrame: Post surgery
measure: Percentage of Participants With 3-year Overall Survival
timeFrame: 3 years
measure: Percentage of Participants With 2-year Disease-free Survival
timeFrame: 2 years
measure: Number of Participants With Frequent (>=15% Grade 3/4 Incidence) Adverse Events Regardless of Attribution
timeFrame: Week 1, 3, 5, 7, 9, 4-6 weeks after therapy and within 30 days post surgery
Other outcomes:
Locations:
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Springfield
country: United States
facility: Simmons Cooper Cancer Institute
state: Illinois
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center and Children's Hospital
state: Oregon
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Washington University School of Medicine
name: A. Craig Lockhart, MD
role: STUDY_CHAIR
References:
citation: Lockhart AC, Reed CE, Decker PA, Meyers BF, Ferguson MK, Oeltjen AR, Putnam JB, Cassivi SD, Montero AJ, Schefter TE; American College of Surgeons Oncology Group. Phase II study of neoadjuvant therapy with docetaxel, cisplatin, panitumumab, and radiation therapy followed by surgery in patients with locally advanced adenocarcinoma of the distal esophagus (ACOSOG Z4051). Ann Oncol. 2014 May;25(5):1039-44. doi: 10.1093/annonc/mdu091. Epub 2014 Feb 20.