Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in 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. Identifier: NCT00831181
Recruitment Status : Completed
First Posted : January 28, 2009
Results First Posted : March 20, 2018
Last Update Posted : March 20, 2018
Information provided by (Responsible Party):
Beth Israel Medical Center

Brief Summary:

RATIONALE: 5FU based neoadjuvant chemoradiation (nCRT) is the standard of care for Stage II/III rectal cancer. Pathologic complete response (pCR) and downstaging have been associated with improved outcomes. The addition of oxaliplatin (OXA) to neoadjuvant therapy may reduce distant disease recurrence. Adjuvant treatment with OXA for rectal cancer has been motivated by benefits demonstrated in stage III colon cancer.

Objective: To determine the feasibility, toxicity, and efficacy of preoperative OXA/5FU and RT followed by total mesorectal excision (TME) and adjuvant

PURPOSE: This phase II trial is studying the side effects and how well giving neo-adjuvant combination chemotherapy with radiation works in treating patients undergoing surgery for rectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: 5-FU Drug: Oxaliplatin Drug: leucovorin Procedure: mesorectal excision Phase 2

Detailed Description:



  • To assess the complete pathologic response rate in patients with rectal cancer treated with radiation, modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.


  • To observe the overall pathologic response rate in these patients.
  • To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
  • To assess toxic side effects of these regimens in these patients.
  • To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.


Patients with stage II/III rectal cancer were treated with OXA 60mg/m2 weekly continuous infusion 5FU of 225 mg/m2/d d1-5 with pelvic RT of 1.8Gy/d for 28 doses. Adjuvant therapy consisted of 6 cycles of biweekly FOLFOX6.

Surgery: Patients undergo total mesorectal excision by anterior resection or an abdominal perineal resection within 4 weeks after completion of neoadjuvant therapy.

Adjuvant therapy: Within 4 weeks after surgery, patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life assessment questionnaires at baseline and at each follow-up visit.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Open-labeled, Prospective Study to Determine the Efficacy of Preoperative Chemoradiation With Oxaliplatin/5-FU in Locally Advanced Rectal Cancer Followed by Total Mesorectal Excision and FOLFOX6
Study Start Date : July 2004
Actual Primary Completion Date : November 2009
Actual Study Completion Date : November 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Preoperative Chemoradiation
Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and 5-FU / leucovorin (FOLFOX 6)
Drug: 5-FU
5-FU: continuous infusion via portable pump during all RT (approximately 33 days)
Other Name: fluorouracil

Drug: Oxaliplatin
Oxaliplatin: 50mg/m2 weekly dosing during RT (Day 1)
Other Name: Eloxatin

Drug: leucovorin
Folinic Acid (Leucovorin): 400 mg/m2; 2-hour IV infusion simultaneously with oxaliplatin
Other Name: Folinic Acid

Procedure: mesorectal excision
mesorectal excision

Primary Outcome Measures :
  1. Pathologic Response and Complete Response [ Time Frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months ]

    Pathologic Response and Complete Response to preoperative therapy will be determined at the time of surgical resection. All grossly visible areas of ulceration and/or induration with be measured and submitted for histological evaluation.

    The unit of measure is the tumor response rate to preoperative chemoradiation.

    Pathologic complete response (pCR) is defined as no evidence of invasive tumor cells on pathologic examination of the primary rectal cancer.

    Tumor regression grade (TRG) will be quantitated into five grades:

    TRG 1 (complete regression) -absence of residual cancer and fibrosis extending from the site of original tumor through the layers of the rectal wall.

    TRG 2 characterized by the presence of rare residual cancer cells scattered through the fibrosis.

    TRG 3 characterized by an increase in the number of residual cancer cells, but fibrosis still predominant.

    TRG 4 -residual cancer outgrowing fibrosis. TRG 5 characterized by absence of regressive changes.

Secondary Outcome Measures :
  1. Treatment Toxicity [ Time Frame: Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months). ]
    Toxicity was assessed weekly during neoadjuvant chemotherapy and radiation therapy, bi-weekly during adjuvant FOLFOX therapy.

  2. Complete Resectability Rates [ Time Frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. ]
    Complete resectability rates assessed by circumferential margin.

  3. Local Regional Control [ Time Frame: median follow-up 22 months post-TME ]
    subjects were followed for median of 22 months post-surgery

  4. Disease-free Survival [ Time Frame: median 22 months follow-up ]
  5. Overall Survival [ Time Frame: median follow-up 22 months ]
  6. Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan [ Time Frame: median follow-up 22 months ]
  7. Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage [ Time Frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. ]
    Thin-section high resolution pelvic MRI was used to image the tumor prior to chemoradiation and repeated prior to surgery, and then compared to post-treatment pathological stage.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • Histologically proven adenocarcinoma of the rectum with no distant metastases.
  • T3-4N0M0, TanyN1-3M0 assessed by clinical exam, TRUS, MRI and CT
  • The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by protoscopic examination.
  • No prior chemotherapy or pelvic irradiation.
  • ECOG performance status 0-1
  • Age 18 to 70 years
  • ANC >= 1500/mm3 and platelets >= 100,000/mm3
  • Serum creatinine <= 1.5 x ULN; bilirubin <= 1.5 x ULN; ALT<= 2.5 x ULN

Exclusion Criteria

  • Pregnant or lactating females; patients not practicing active contraception while sexually active.
  • No other serious medical condition
  • A psychiatric disorder that would prohibit the subject from participating fully.
  • Peripheral neuropathy > grade 1
  • History within the past 5 years of a cancer diagnosis except for non-melanomatous skin cancers or in situ cervix carcinoma.
  • HIV positive patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00831181

United States, New York
Beth Israel Medical Center - Philipps Ambulatory Care Center
New York, New York, United States, 10003
St. Luke's-Roosevelt Hospital Center - Roosevelt Division
New York, New York, United States, 10019
Sponsors and Collaborators
Beth Israel Medical Center
Principal Investigator: Peter Kozuch, MD Beth Israel Medical Center

Responsible Party: Beth Israel Medical Center Identifier: NCT00831181     History of Changes
Other Study ID Numbers: CDR0000633360
BIMCP-OX-08-006 ( Registry Identifier: BIMCP-OX-08-006 )
AVENTIS-BIMCP-OX-08-006 ( Other Grant/Funding Number: AVENTIS-BIMCP-OX-08-006 )
First Posted: January 28, 2009    Key Record Dates
Results First Posted: March 20, 2018
Last Update Posted: March 20, 2018
Last Verified: February 2018

Keywords provided by Beth Israel Medical Center:
stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Folic Acid
Antineoplastic Agents
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances