Clinical trial NCT00527111: Pre-op Rectal ChemoRad +/- Cetuximab
Official title: A Randomized Phase II Trial of Pre-operative Chemoradiotherapy With or Without Cetuximab (ERBITUX(R)) in Locally-advanced Adenocarcinoma of the Rectum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rectal Cancer
Lead sponsor: US Oncology Research
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
name: Eli Lilly and Company
First posted: 2007-09-10
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Pathologic Response Rate (pCR) With 95% Confidence Interval.
timeFrame: 5 years
Secondary outcomes:
measure: To Determine Objective Response Rate (ORR) Based on RECIST Local Recurrence-free Survival in These Patient Groups; Overall and Recurrence-free Survival in These Cohorts.
timeFrame: 5 years
measure: 5- Year Overall Survival (OS) Rate
timeFrame: 5 years
measure: Recurrence-free Survival (RFS) Rate at 5 Years
timeFrame: 5 years
measure: KRAS Mutation Rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Oncology Associates D.B.A. Hematology Oncology Physicians & Extenders
state: Arizona
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates
state: Florida
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida, P.A.
state: Florida
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland, PC
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Cancer Centers-Southwest
state: Kansas
city: Westminster
country: United States
facility: Alliance Hematology Oncology PA
state: Maryland
city: Columbia
country: United States
facility: Missouri Cance Associates
state: Missouri
city: St. Joseph
country: United States
facility: St. Joseph Oncology, Inc.
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina
state: North Carolina
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Amarillo
country: United States
facility: Texas Oncology - Amarillo
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cance Center
state: Texas
city: Beaumont
country: United States
facility: Mamie McFaddin Ward Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Methodist Charlton Cancer Ctr.
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Ctr
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Lewisville
country: United States
facility: Lake Vista Cancer Center
state: Texas
city: Longview
country: United States
facility: Longview Cance Center
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: Odessa
country: United States
facility: Texas Oncology-Odessa
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: San Antonio
country: United States
facility: HOAST - Medical Dr.
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center - Sherman
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology Cancer Center-Sugar Land
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care and Research
state: Texas
city: Webster
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Wichita Falls
country: United States
facility: Texoma Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-South
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists-Vancouver
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Mem Hosp/North Star Lodge
state: Washington
city: Beckley
country: United States
facility: Raleigh Regional Cancer Center
state: West Virginia
Study officials:
affiliation: US Oncology Research
name: Andrew D McCollum, MD
role: PRINCIPAL_INVESTIGATOR
References: