Radiation Therapy and Fluorouracil With or Without Combination Chemotherapy Followed by Surgery in Treating Patients With Stage II or Stage III Rectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Timing of Rectal Cancer Response to Chemoradiation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00335816
• Other study ID #: mskcc 12-201
• Secondary ID: P30CA033572CHNMC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 2008
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Fluorouracil may also make tumor cells more sensitive to radiation therapy. Leucovorin calcium may protect normal cells from the side effects of chemotherapy, and it may help fluorouracil work better by making tumor cells more sensitive to the drug. Giving radiation therapy together with chemotherapy 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 radiation therapy together with fluorouracil with or without combination therapy works in treating patients who are undergoing surgery for stage II or stage III rectal cancer.

Description:

OBJECTIVES:

I. To determine the rate of pathologic complete response to chemoradiation (no evidence of residual tumor in the resected specimen) of Stage II and Stage III rectal cancers that are staged preoperatively by endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI), treated according to a standardized chemoradiation and surgery protocol, and evaluated by a systematic pathologic exam of the surgical specimen.

II. To study the effect of different chemoradiation-to-surgery intervals on the rate of pathologic complete response, on surgical difficulty, and on postoperative complications.

III. To investigate the feasibility of using sensitive molecular assays to detect tumor cells in the tumor bed and regional lymph nodes of rectal cancer specimens, with or without pathologic complete response to preoperative chemoradiation.

OUTLINE:

Patients are assigned to 1 of 4 treatment groups. All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil intravenously (IV) continuously over 24 hours 7 days a week for 6 weeks.

GROUP I (closed to enrollment): Patients undergo standard surgical resection after completion of chemoradiation therapy.

GROUP II (closed to enrollment): Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2. Treatment repeats every 14 days for 2 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

GROUP III: Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 4 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

GROUP IV: Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 6 courses. After the last week of post- radiation chemotherapy, patients undergo standard surgical resection.

In all groups, treatment continues in the absence of disease progression or unacceptable toxicity. A

fter completion of study treatment, patients are followed up for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 248
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1, or comparable Karnofsky performance status

• Patients must have histologically confirmed invasive adenocarcinoma of the rectum Distal border of the tumor must be within 12 cm from the anal verge as measured on rigid proctoscopic exam

• Patients must have Stage II (uT3-4, uN0) or Stage III (any T, uN1-2) tumors, as confirmed by ERUS or MRI; females with anterior tumors invading the posterior vaginal wall (uT4) and males with anterior tumors that invade the seminal vesicles or adjacent organs (uT4) will also be eligible provided they undergo an extended resection including the organs involved

• Patients with high grade obstruction that impedes the ERUS exam are eligible for the study provided they can be staged by MRI

• Patients with synchronous or metachronous colorectal cancer are eligible for the study on condition that they are treated for rectal cancer in accordance with the protocol

• Patients with the following are NOT allowed on study:

• Metastatic disease or other primaries

• Locally recurrent rectal cancer

• Previously documented history of Familial Adenomatous Polyposis

• History of Inflammatory Bowel Disease

• History of prior radiation treatments to pelvis

• History of clinically significant cardiac disease (i.e., Class 3-4 congestive heart failure, symptomatic coronary artery disease, uncontrolled arrhythmia, and/or myocardial infarction within the previous 6 months

• History of uncontrolled seizures or clinically significant central nervous system disorders

• History of psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance

• History of allergy and/or hypersensitivity to 5-fluorouracil (fluorouracil), leucovorin (leucovorin calcium), and/or oxaliplatin

• History of difficulty or inability to take or absorb oral medications

• Patients must have adequate bone marrow, hepatic and renal function within 7 days prior to registration

• White blood cells (WBC) >= 3,000 mm^3

• Absolute neutrophil count (ANC) > 1,500 mm^3

• Hemoglobin > 9.5 mg/dl

• Platelet count >= 100,000 mm^3

• Total bilirubin =< 1.5 mg/dl

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.0 times institutional upper limit of normal (ULN)

• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.0 times ULN

• Alkaline phosphatase =< 2.0 times ULN

• Serum creatinine =< 1.5 times ULN

• Patients with hereditary non-polyposis colorectal cancer are eligible for the study provided they meet the rest of the eligibility criteria

• Patients who have experienced a prior malignancy should have received potentially curative therapy for that malignancy, and should be cancer-free for at least five years from the date of initial diagnosis (Exceptions: patients treated for basal cell carcinoma, or carcinoma in-situ of the cervix)

• Patients of reproductive potential should agree to use an effective method of birth control when undergoing treatments with known or possible mutagenic or teratogenic effects; all female participants of childbearing potential must have a negative urine or serum pregnancy test within two weeks prior to study registration

• Patients or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of protected health information; NOTE: this may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration or the initiation of any study-specific procedures

Related Conditions & MeSH terms

• Colorectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• fluorouracil
Given IV
• leucovorin calcium
Given IV
• oxaliplatin
Given IV

Procedure:
• conventional surgery
Patients undergo surgery

Radiation:
• radiation therapy
Patients undergo radiotherapy

Other:
• laboratory biomarker analysis
Correlative studies

Genetic:
• DNA analysis
Correlative studies
• polymerase chain reaction
Correlative studies

Other:
• immunohistochemistry staining method
Correlative studies

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
United States	Vermont Cancer Center at University of Vermont	Burlington	Vermont
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Cancer Care Center at John Muir Health - Concord Campus	Concord	California
United States	City of Hope Medical Center	Duarte	California
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Colon and Rectal Surgery, Incorporated	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of pathologic complete response		Determined at the time of surgery
Primary	Effect of different chemoradiation-to-surgery intervals on rate of pathologic complete response and surgical difficulty.		Measured at the time of surgery
Primary	Effect of different chemoradiation-to-surgery intervals on postoperative complications		30 days after surgery

External Links

•   Memorial Sloan Kettering Cancer Center