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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Radiation: radiation therapy; Procedure: conventional surgery

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Hunterdon Regional Cancer Center
    • Lakewood, New Jersey, United States, 08701
      • Kimball Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County
    • Red Bank, New Jersey, United States, 07701
      • Riverview Medical Center
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Trenton, New Jersey, United States, 08629
      • St. Francis Medical Center
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Bon Secours-Holy Family Health System
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • Harrisburg, Pennsylvania, United States, 17105-8700
      • Pinnacle Health Hospitals
    • Johnstown, Pennsylvania, United States, 15905
      • Conemaugh Memorial Hospital
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Regional Center
    • Lansdale, Pennsylvania, United States, 19446
      • North Penn Hospital
    • Paoli, Pennsylvania, United States, 19301-1792
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pottstown, Pennsylvania, United States, 19464
      • Pottstown Memorial Regional Cancer Center
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • West Grove, Pennsylvania, United States, 19390
      • Southern Chester County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of toxicity	weekly during treatment
tolerated dose of preoperative hyperfractionated radiation and concurrent chemotherapy	during radiation therapy and chemotherapy

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: July 1, 1996
• Primary Completion (Actual): July 1, 2001
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: April 12, 2004
• First Posted (Estimate): April 13, 2004

Study Record Updates

• Last Update Posted (Actual): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage II rectal cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000068776; P30CA006927 (U.S. NIH Grant/Contract); FCCC-96071; NCI-G01-1988