Radiation Therapy and Chemotherapy Followed by Surgery and Combination Chemotherapy in Treating Patients With Rectal Cancer

Sponsor

Fox Chase Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00021398

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

266

Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy and chemotherapy may shrink the tumor so that it can be removed during surgery.

PURPOSE: Phase II trial to study the effectiveness of radiation therapy and chemotherapy followed by surgery and combination chemotherapy in treating patients who have stage II or stage III rectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: fluorouracil Drug: leucovorin calcium Procedure: conventional surgery Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES: I. Determine the local recurrence rate, disease-free survival, and overall survival of patients with stage II or III rectal cancer treated with neoadjuvant radiotherapy and fluorouracil followed by surgical resection and adjuvant fluorouracil and leucovorin calcium. II. Determine the toxicity rate in patients treated with this regimen. III. Correlate failure-free survival with ultrasound-determined preoperative staging in patients treated with this regimen. IV. Determine the quality of life of patients treated with this regimen. V. Determine if toxicity due to treatment, daily stool frequency, sexual dysfunction, and disease-free survival correlates with quality of life parameters in patients treated with this regimen. VI. Correlate clinical selection criteria with ability to perform sphincter-sparing surgery in patients treated with this regimen. VII. Determine post-chemoradiotherapy pathological response, margin status, and lymph node status and correlate these factors with initial clinico-pathologic findings in patients treated with this regimen.

OUTLINE: Patients undergo pelvic radiotherapy once daily five days a week for 5 weeks followed by boost radiotherapy twice daily for 7 days. Patients also receive neoadjuvant fluorouracil IV continuously over days 1-4 and 36-40. Patients undergo surgical resection 4-6 weeks after completion of radiotherapy. At 4 weeks after surgery, patients receive adjuvant leucovorin calcium IV and fluorouracil IV once daily five days a week. Treatment continues every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at the completion of pelvic and boost radiotherapy, at 4 weeks after completion of chemoradiotherapy (prior to surgery), and then at 3, 6, and 12 months after completion of study therapy. Patients are followed every 3 months for 2 years, every 4 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 23-41 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study: Hyperfractionated Pre-Op Chemo-Radiation for Locally Advanced Rectal Cancer

Study Start Date :

Jul 1, 1996

Actual Primary Completion Date :

Jul 1, 2001

Actual Study Completion Date :

Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiation Therapy, Chemotherapy and Surgery	Drug: fluorouracil Drug: leucovorin calcium Procedure: conventional surgery Radiation: radiation therapy

Arm

Intervention/Treatment

Experimental: Radiation Therapy, Chemotherapy and Surgery

Drug: fluorouracil

Drug: leucovorin calcium

Procedure: conventional surgery

Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

Frequency of toxicity [weekly during treatment]
tolerated dose of preoperative hyperfractionated radiation and concurrent chemotherapy [during radiation therapy and chemotherapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
Tumor extending through bowel wall (T3) OR
Fixation to surrounding structures (T4) OR
Nodal involvement by endorectal ultrasound (N1-2)
Tumor extending through bowel wall, but not fixed (T3) must be:
At least 4 cm or at least 40% of bowel circumference OR
Accompanied by nodal involvement
Evidence of transmural penetration confirmed by 2 of the following:
CT scan
Pelvic MRI
Transrectal ultrasound
Physical exam
Proximal extent of tumor must not extend higher than 12 cm above dentate line and must be below pelvic peritoneal reflexion or sacral promontory
Regional lymph node involvement allowed
No distant metastases by CT scan of abdomen and pelvis or chest x-ray

PATIENT CHARACTERISTICS:

Age: Over 18
Performance status: ECOG 0-1
Life expectancy: At least 2 years
Hematopoietic:
Leukocyte count greater than 4,000/mm3
Platelet count at least 100,000/mm3
Hemoglobin greater than 10 g/dL
Hepatic:
SGOT and SGPT less than 1.5 times normal
Bilirubin less than 1.5 mg/dL
Renal: Creatinine less than 1.8 mg/dL
Other:
Not pregnant or nursing
Negative pregnancy test
No other prior or concurrent malignancy within the past 5 years except inactive non-melanoma skin cancer or carcinoma in situ of the cervix
No psychiatric condition that would preclude informed consent
No other serious medical illness that would limit survival

PRIOR CONCURRENT THERAPY:

Biologic therapy: Not specified
Chemotherapy: No prior chemotherapy for rectal cancer
Endocrine therapy: Not specified
Radiotherapy: No prior radiotherapy for rectal cancer
Surgery: No prior surgery for rectal cancer, except diagnostic biopsy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hunterdon Regional Cancer Center	Flemington	New Jersey	United States	08822
2	Kimball Medical Center	Lakewood	New Jersey	United States	08701
3	Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County	Mount Holly	New Jersey	United States	08060
4	Riverview Medical Center	Red Bank	New Jersey	United States	07701
5	Community Medical Center	Toms River	New Jersey	United States	08755
6	St. Francis Medical Center	Trenton	New Jersey	United States	08629
7	Bon Secours-Holy Family Health System	Altoona	Pennsylvania	United States	16602
8	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
9	Pinnacle Health Hospitals	Harrisburg	Pennsylvania	United States	17105-8700
10	Conemaugh Memorial Hospital	Johnstown	Pennsylvania	United States	15905
11	Saint Mary Regional Center	Langhorne	Pennsylvania	United States	19047
12	North Penn Hospital	Lansdale	Pennsylvania	United States	19446
13	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
14	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
15	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania	United States	19464
16	Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
17	Southern Chester County Medical Center	West Grove	Pennsylvania	United States	19390