Panitumumab, Docetaxel, Cisplatin, Radiation Therapy, and Surgery in Treating Patients With Newly Diagnosed, Locally Advanced Esophageal Cancer or Cancer of the Gastroesophageal Junction

Esophageal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00757172
• Other study ID #: ACOSOG-Z4051
• Secondary ID: ACOSOG-Z4051CDR0
• Status: Completed
• Phase: Phase 2
• First received: September 22, 2008
• Last updated: February 10, 2016
• Start date: January 2009
• Est. completion date: December 2014

Study information

• Verified date: February 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2014
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Biological:
• panitumumab

Drug:
• cisplatin

• docetaxel

Procedure:
• neoadjuvant therapy

• therapeutic conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Evanston Hospital	Evanston	Illinois
United States	Wayne Hospital	Greenville	Ohio
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Simmons Cooper Cancer Institute	Springfield	Illinois
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	Amgen, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Pathologic Complete Response Following Surgery	Pathologic complete response (pCR) was defined as no viable residual tumor cells. A cellular residual mucin pools should be noted but also considered a pathologic complete response.	Post surgery	No
Secondary	Number of Participants With Near-complete Response Rate (= 10% Residual Cancer in Primary Tumor Viable)		Post surgery	No
Secondary	Percentage of Participants With 3-year Overall Survival	Survival time was defined to be the length of time from start of study therapy to death due to any cause or until last follow-up (censored value).	3 years	No
Secondary	Percentage of Participants With 2-year Disease-free Survival	Disease-free survival was defined as the time from start of study therapy to documentation of disease recurrence. Participants who died without documentation of recurrence were considered to have had tumor recurrence at the time of death unless there was documented evidence that no recurrence occured before death. Participants who failed to return for evaluation after beginning therapy were censored for recurrence on the last day of therapy. Participants who experienced major treatment violations were censored for recurrence on the date the treatment violation occured.	2 years	No
Secondary	Number of Participants With Frequent (>=15% Grade 3/4 Incidence) Adverse Events Regardless of Attribution	Adverse events were assessed by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening; and grade 5= death.	Week 1, 3, 5, 7, 9, 4-6 weeks after therapy and within 30 days post surgery	Yes