Pre-op Rectal ChemoRad +/- Cetuximab

Rectal Cancer Clinical Trial

Official title:

A Randomized Phase II Trial of Pre-operative Chemoradiotherapy With or Without Cetuximab (ERBITUX(R)) in Locally-advanced Adenocarcinoma of the Rectum

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00527111
• Other study ID #: 05102
• Secondary ID: CA225269
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2007
• Last updated: November 7, 2015
• Start date: February 2007
• Est. completion date: January 2015

Study information

• Verified date: November 2015
• Source: US Oncology Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to find out what effects (good and bad) cetuximab has on rectal cancer.

Description:

Rectal cancer remains a significant cause of morbidity and mortality in the United States. Standard treatment for patients with locally advanced rectal cancer generally includes combined chemotherapy and radiotherapy administered either before (neoadjuvant) or after (adjuvant) definitive surgical resection. Published data from Germany has suggested advantages to a neoadjuvant strategy. Currently, the standard concurrent chemoradiotherapy regimen in the United States is pelvic irradiation administered concurrently with 5-fluorouracil (5-FU) given as a protracted venous infusion. However, local recurrence remains a problem. Recently completed randomized trials of chemoradiotherapy have demonstrated local recurrence rates between 8-17% even with currently accepted standard chemoradiotherapy and adequate surgical management.

Several recent trials have explored the use of radiotherapy and cetuximab with good results.

Because of the non-overlapping toxicity profiles and the potentially diverse and complimentary mechanisms of action, the combination of chemotherapy plus ERBITUX given concurrently with pelvic radiotherapy may improve on the outcomes seen with current standards for patients with locally advanced adenocarcinoma of the rectum.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Note: Please see Section 8.1 for the necessary "Prestudy Assessments".

A patient will be eligible for inclusion in this study if s/he meets all of the following criteria:

• Has a histologically confirmed diagnosis of newly diagnosed adenocarcinoma of the rectum (tumor within 15 cm of the anal verge). Location of tumor (lower 1/3rd vs. middle or upper 1/3rd) and pre-treatment nodal status (N0 vs. N1 or N2) will be recorded in the eCRF. Patients with only non-measurable disease are eligible as long as they meet the other disease requirements in this criterion as well as all other eligibility criteria.

• Has tumor that is locally advanced (T3/T4 or lymph node positive) by preoperative assessment with CT or MRI imaging or transrectal ultrasonography.

• Has no evidence of distant metastases by radiographic staging

• Has an ECOG Performance Status (PS) 0-1

• Is greater than 18 years of age

• Has adequate marrow and organ system function as assessed by the following lab values:

White blood cell (WBC) count See protocol for specific details Absolute neutrophil count (ANC) See protocol for specific details Hemoglobin See protocol for specific details Total bilirubin See protocol for specific details AST and ALT See protocol for specific details Serum creatinine See protocol for specific details Platelet count See protocol for specific details

• Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.

Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.

All WOCBP MUST have a negative pregnancy test within 3 weeks prior to registration (confirmed within 7 days prior to first receiving investigational product). If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.

In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (eg, missed or late menstrual period) at any time during study participation.

The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.

• Has signed a Patient Informed Consent Form

• Has signed a Patient Authorization Form

Exclusion Criteria:

• A patient will be excluded from this study if s/he meets any of the following criteria:

• Has another disease similar to one being studied (ie, colon cancer)

• Has evidence of distant metastases by radiographic staging

• Has had prior treatment for the current disease

• Has had prior stem cell or bone marrow transplant or any organ transplant with the exception of corneal transplant or cadaver bone graft

• Has a history of hypersensitivity to any of study treatments

• Has had a prior severe infusion reaction to a monoclonal antibody

• Has received prior therapy, at any time, which specifically and directly targets the EGFR pathway

• Has a significant history of uncontrolled cardiac disease; ie, uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, or cardiomyopathy with decreased ejection fraction

• Has evidence of CNS involvement (CNS imaging is not required for study enrollment unless clinically suspected CNS disease is present.)

• Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection or Gilbert's Syndrome

• Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs. Patients, who have received prior radiotherapy to any regional site other than the pelvis, as long as all other inclusion criteria are met, could be considered for enrollment after discussion with Dr. McCollum.

• Is a pregnant or nursing woman

• Is unable to comply with requirements of study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer

Intervention

Drug:
• Cetuximab

• 5-fluorouracil

Radiation:
• Pelvic irradiation

Locations

Country	Name	City	State
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	Texas Oncology Cance Center	Austin	Texas
United States	Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Raleigh Regional Cancer Center	Beckley	West Virginia
United States	Highline Medical Oncology	Burien	Washington
United States	Missouri Cance Associates	Columbia	Missouri
United States	Methodist Charlton Cancer Ctr.	Dallas	Texas
United States	Texas Cancer Center at Medical City	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Texas Cancer Center	Denton	Texas
United States	El Paso Cancer Treatment Ctr	El Paso	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Texas Oncology, P.A.	Fort Worth	Texas
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Lake Vista Cancer Center	Lewisville	Texas
United States	Longview Cance Center	Longview	Texas
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Advanced Medical Specialties	Miami	Florida
United States	Allison Cancer Center	Midland	Texas
United States	Cancer Care & Hematology Specialists of Chicagoland, PC	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Cancer Centers of Florida, P.A.	Ocoee	Florida
United States	Texas Oncology-Odessa	Odessa	Texas
United States	Kansas City Cancer Centers-Southwest	Overland Park	Kansas
United States	Paris Regional Cancer Center	Paris	Texas
United States	Cancer Centers of North Carolina	Raleigh	North Carolina
United States	HOAST - Medical Dr.	San Antonio	Texas
United States	Texas Cancer Center - Sherman	Sherman	Texas
United States	Cancer Care Northwest-South	Spokane	Washington
United States	St. Joseph Oncology, Inc.	St. Joseph	Missouri
United States	Texas Oncology Cancer Center-Sugar Land	Sugar Land	Texas
United States	Oncology Associates D.B.A. Hematology Oncology Physicians & Extenders	Tucson	Arizona
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists-Vancouver	Vancouver	Washington
United States	Texas Oncology Cancer Care and Research	Waco	Texas
United States	Texas Oncology, P.A.	Webster	Texas
United States	Alliance Hematology Oncology PA	Westminster	Maryland
United States	Texoma Cancer Center	Wichita Falls	Texas
United States	Yakima Valley Mem Hosp/North Star Lodge	Yakima	Washington

Sponsors (3)

Lead Sponsor	Collaborator
US Oncology Research	Bristol-Myers Squibb, ImClone LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective of this study is to determine the pathologic response rate, using tumor regression grading, to treatment with preoperative chemoradiotherapy (pelvic radiotherapy with concurrent 5-FU) with and without concurrent ERBITUX.		7 weeks	No
Secondary	To determine response rate based on RECIST; the toxicity rates in patients who receive preoperative chemoradiotherapy with or without ERBITUX; local recurrence-free survival in these patient groups; overall and recurrence-free survival in these cohorts.		7 weeks	No