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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00003799
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 10, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date January 10, 2013
Study Start Date  ICMJE May 1999
Actual Primary Completion Date September 2003   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 9, 2013)
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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Locally Advanced Rectal Cancer
Official Title  ICMJE 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
Brief Summary 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.

Interventions:
  • Drug: fluorouracil
  • Drug: oxaliplatin
  • Radiation: radiation therapy
  • Drug: leucovorin calcium
  • Procedure: therapeutic conventional surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: April 9, 2007)
20
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date September 2003   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00003799
Other Study ID Numbers  ICMJE NCI-2012-03145
E1297
U10CA021115 ( U.S. NIH Grant/Contract )
CDR0000066943 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel Haller Eastern Cooperative Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP