Clinical trial NCT00021398: Radiation Therapy and Chemotherapy Followed by Surgery and Combination Chemotherapy in Treating Patients With Rectal Cancer
Official title: Phase II Study: Hyperfractionated Pre-Op Chemo-Radiation for Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-13
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of toxicity
timeFrame: weekly during treatment
measure: tolerated dose of preoperative hyperfractionated radiation and concurrent chemotherapy
timeFrame: during radiation therapy and chemotherapy
Secondary outcomes:
Other outcomes:
Locations:
city: Flemington
country: United States
facility: Hunterdon Regional Cancer Center
state: New Jersey
city: Lakewood
country: United States
facility: Kimball Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County
state: New Jersey
city: Red Bank
country: United States
facility: Riverview Medical Center
state: New Jersey
city: Toms River
country: United States
facility: Community Medical Center
state: New Jersey
city: Trenton
country: United States
facility: St. Francis Medical Center
state: New Jersey
city: Altoona
country: United States
facility: Bon Secours-Holy Family Health System
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Harrisburg
country: United States
facility: Pinnacle Health Hospitals
state: Pennsylvania
city: Johnstown
country: United States
facility: Conemaugh Memorial Hospital
state: Pennsylvania
city: Langhorne
country: United States
facility: Saint Mary Regional Center
state: Pennsylvania
city: Lansdale
country: United States
facility: North Penn Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pottstown
country: United States
facility: Pottstown Memorial Regional Cancer Center
state: Pennsylvania
city: Reading
country: United States
facility: Reading Hospital and Medical Center
state: Pennsylvania
city: West Grove
country: United States
facility: Southern Chester County Medical Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Joshua Meyer, MD
role: PRINCIPAL_INVESTIGATOR
References: