Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Rectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003799
First received: November 1, 1999
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

Phase I trial to study the effectiveness of radiation therapy plus chemotherapy followed by surgery and additional chemotherapy in treating patients who have advanced nonmetastatic primary cancer of the rectum. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, radiation therapy, and surgery may be an effective treatment for rectal cancer


Condition Intervention Phase
Adenocarcinoma of the Rectum
Mucinous Adenocarcinoma of the Rectum
Signet Ring Adenocarcinoma of the Rectum
Stage IIA Rectal Cancer
Stage IIB Rectal Cancer
Stage IIC Rectal Cancer
Stage IIIA Rectal Cancer
Stage IIIB Rectal Cancer
Stage IIIC Rectal Cancer
Drug: fluorouracil
Drug: oxaliplatin
Radiation: radiation therapy
Drug: leucovorin calcium
Procedure: therapeutic conventional surgery
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Preoperative Radiation Therapy With Concurrent Protracted Continuous Infusion 5-FU and Dose Escalating Oxaliplatin Followed by Surgery, 5-FU, and Leucovorin for Locally Advanced (T3 and T4) Rectal Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of oxaliplatin when combined with radiation therapy and fluorouracil based on the incidence of DLT as assessed by CTC version 2.0 [ Time Frame: 5 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: May 1999
Primary Completion Date: September 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, radiotherapy, surgery)

Patients receive fluorouracil IV continuously with concurrent radiotherapy for 5.5 weeks. Patients also receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5.

Patients undergo surgery 6-8 weeks after completing preoperative chemotherapy and radiotherapy. The surgical procedure is determined by the extent of the tumor before preoperative therapy. The type of operative procedure may be abdominoperineal resection, low anterior resection (LAR), or LAR/coloanal anastomosis.

Postoperative chemotherapy begins within 6 weeks after surgery, comprising leucovorin calcium and fluorouracil IV on days 1-5. Treatment repeats every 21 days for 4 courses.

Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Procedure: therapeutic conventional surgery
Undergo surgery

Detailed Description:

PRIMARY OBJECTIVES:

I. To identify maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of oxaliplatin when combined preoperatively with concurrent radiation therapy (XRT) and fluorouracil (5-FU) by PVI.

II. To evaluate the resection rate for T4 rectal cancers, the pathologic CR rate for T3 and T4 rectal cancers, and the expected versus actual type of resection (APR vs. LAR vs. LAR/coloanal anastomosis).

III. To make preliminary observations of patient survival and patterns of recurrence for this treatment combination.

IV. To evaluate anastomotic and sphincter function following pre-op combined modality therapy.

OUTLINE: This is a dose-escalation study of preoperative oxaliplatin.

Patients receive fluorouracil IV continuously with concurrent radiotherapy for 5.5 weeks. Patients also receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5.

Cohorts of 5 patients each receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 5 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

Patients undergo surgery 6-8 weeks after completing preoperative chemotherapy and radiotherapy. The surgical procedure is determined by the extent of the tumor before preoperative therapy. The type of operative procedure may be abdominoperineal resection, low anterior resection (LAR), or LAR/coloanal anastomosis.

Postoperative chemotherapy begins within 6 weeks after surgery, comprising leucovorin calcium and fluorouracil IV on days 1-5. Treatment repeats every 21 days for 4 courses.

Patients are followed every 3 months for 2.5 years, every 6 months for 3 years, then annually for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, locally advanced, non-metastatic primary T3 or T4 primary adenocarcinoma of the rectum
  • No evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
  • No intra-operative radiotherapy (IORT) or brachytherapy will be allowed
  • The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of anal verge by proctoscopic examination
  • Transmural penetration of tumor through the muscularis propria must be demonstrated by either of the following:

    • CT scan plus endorectal ultrasound or
    • MRI
  • Tumors must be defined prospectively by the surgeon as clinically resectable or not; clinically resectable tumors will be defined by the surgeon as mobile and completely resectable with negative margins based on the routine examination of the non-anesthetized patient; before pre-op treatment, the surgeon should estimate and record the type of resection anticipated: APR, LAR, or LAR/coloanal anastomosis
  • The tumor may be clinically fixed or initially not completely resectable, clinical stage T4, N0-2, M0 based on the presence of at least one of the following criteria:

    • Clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall or sacrum
    • Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack of clear tissue plane will be considered evidence of fixation
    • Hydronephrosis on CT scan or IVP or ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy, or invasion into prostate
    • Vaginal or uterine involvement
  • ECOG performance status 0-2 and surgical evaluation confirms the patient's medical condition would tolerate the proposed surgical procedure
  • Caloric intake should be >= 1500 kilocalories/d
  • WBC >= 3500/uL
  • Platelets >= 100,000/uL
  • Serum creatinine =< 2.0 mg/dL
  • Serum bilirubin less than 2.0 mg/dL
  • Alk Phos =< 2 x ULN
  • SGOT =< 2 x ULN
  • CEA should be determined prior to initiation of therapy
  • Absence of clinical evidence of high-grade (lumen diameter < 1cm) large bowel obstruction, unless diverting colostomy has been performed
  • Pregnant or lactating women are not eligible
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
  • No prior chemotherapy or pelvic irradiation therapy
  • No previous or concurrent malignancy is allowed, except:

    • Nonmelanoma skin cancer or in situ cervical cancer
    • Treated non-pelvic cancer from which the patient has been continuously disease free more than five years
  • No active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003799

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Daniel Haller Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003799     History of Changes
Other Study ID Numbers: NCI-2012-03145, E1297, U10CA021115, CDR0000066943
Study First Received: November 1, 1999
Last Updated: January 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 23, 2014