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Oxaliplatin, Leucovorin, and Fluorouracil Before and After Radiation Therapy and Surgery in Treating Patients With Rectal Cancer That Can Be Removed by Surgery (COPERNICUS)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01263171
First Posted: December 20, 2010
Last Update Posted: September 21, 2016
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.
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Cardiff University
  Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying giving oxaliplatin, leucovorin, and fluorouracil together, before and after radiation therapy and surgery in treating patients with rectal cancer that can be removed by surgery.


Condition Intervention Phase
Colorectal Cancer Drug: Leucovorin Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Radiation: radiation therapy Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Stratified Phase II Study of Neoadjuvant Chemotherapy Given Before SCPRT as Treatment for Patients With MRI-Staged Operable Rectal Cancer at High Risk of Metastatic Relapse

Further study details as provided by Cardiff University:

Primary Outcome Measures:
  • Proportion of patients who commence neoadjuvant chemotherapy and radiotherapy and then undergo surgical resection [ Time Frame: Two years ]

Secondary Outcome Measures:
  • Feasibility in terms of achieved dose intensity for chemotherapy and radiotherapy [ Time Frame: Two years ]
  • Safety in terms of NCI CTCAE v 4 toxicities up to 30 days postoperatively and late toxicity at 1 year after surgery [ Time Frame: Two years ]
  • Complete response [ Time Frame: Two years ]
  • Efficacy in terms of down-staging rectal cancer [ Time Frame: Two years ]
  • Local recurrence-free, distant metastasis-free, and overall survival at 1 year after surgery [ Time Frame: Two years ]

Enrollment: 60
Study Start Date: April 2012
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Neo-adjuvant chemotherapy
Neo-adjuvant chemotherapy prior to short course pre-operative radiotherapy followed by adjuvant chemotherapy.
Drug: Leucovorin Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

Primary

  • To assess the feasibility of introducing 8 weeks of neoadjuvant oxaliplatin and fluorouracil followed by radiotherapy and immediate surgical resection in patients with resectable adenocarcinoma of the rectum.

Secondary

  • Determine feasibility of achieving dose intensity for chemotherapy and radiotherapy in these patients.
  • Determine the safety, in terms of NCI CTCAE version 4 toxicities, including postoperative complication rate (up to 30 days postoperatively), and late toxicity assessment at 1 year following surgery, in these patients.
  • Determine how active is the neoadjuvant chemotherapy, in terms of down staging the rectal cancer, local recurrence-free, distant metastasis-free, and overall survival at 1 year following surgery in these patients.

Neoadjuvant therapy: Patients receive oxaliplatin and leucovorin (L-leucovorin or leucovorin calcium) IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Radiotherapy/Surgery: Beginning 1 week after completion of chemotherapy, patients undergo radiotherapy, followed by surgical resection of their primary tumor, within 7-14 days after completion of radiotherapy. Between 6-8 weeks following surgery, patients begin adjuvant therapy.

Adjuvant therapy: Patients receive oxaliplatin and leucovorin (L-leucovorin or leucovorin calcium) IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 2 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Blood and biopsy specimens are collected at baseline and periodically for translational research studies.

After completion of study therapy, patients are followed up periodically for 1 year.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histopathologically confirmed rectal adenocarcinoma meeting the following criteria:

    • Inferior aspect of tumor is > 4 cm from anal verge on digital examination and pelvic MRI scan
    • Superior aspect of tumor is not higher than the anterior aspect of the S1/S2 interspace on pelvic MRI scan
    • Mesorectal fascia is not threatened or involved (tumor > 1 mm from mesorectal fascia)
    • Primary tumor meets 1 of the following criteria:

      • T3a-b (mesorectal primary tumor invasion seen ≤ 5 mm beyond muscularis propria) in the presence of 1 of the following:

        • Extra-mural vascular invasion
        • Mesorectal lymph node(s)/tumor deposit(s) with irregular border and mixed signal intensity
      • Any T3c (primary tumor invasion seen > 5 mm beyond muscularis propria)-T4a (invasion of visceral peritoneum for tumors with a component above peritoneal reflection)
    • Low tumors should not involve levator ani (> 1 mm gap between tumor and levator ani) or anal sphincters
  • No evidence of distant metastases or stage T4b cancer with invasion into adjacent organs or structures
  • Must have measurable disease at the baseline visit
  • Impending rectal obstruction is permitted if relieved by a non-functioning ileostomy or colostomy
  • No disease threatening mesorectal fascia (disease ≤ 1 mm from mesorectal fascia whether this is primary tumor, extra-mural vascular invasion, or tumor deposit with irregular border and mixed signal intensity)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Hemoglobin ≥ 9 g/dL
  • WBC ≥ 3 x 10^9/L
  • Absolute neutrophil count ≥ 1.5 x10^9/L
  • Platelet count ≥ 100 x10^9/L
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 5 x ULN
  • AST or ALT ≤ 2.5 x ULN
  • Creatinine clearance ≥ 50 mL/min
  • Magnesium and calcium normal
  • Candidate for systemic therapy, in the opinion of the primary oncologist
  • No known significant impairment of intestinal absorption (e.g., chronic diarrhea, inflammatory bowel disease)
  • No evidence of established or acute ischemic heart disease (e.g., left bundle branch block, pathological q-waves, ST elevation, or ST-segment depression) and normal clinical cardiovascular assessment by ECG
  • No enlarged pelvic sidewall lymph nodes
  • No severe local bowel symptoms of tenesmus or irregularity or frequency of bowel habit precluding accurate assessment of diarrhea
  • No pelvic sepsis
  • No uncontrolled infection
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during treatment and for 6 months after completion of treatment
  • No other prior or current malignant disease that, in the judgement of the treating investigator, is likely to interfere with study treatment or assessment of response
  • No clinically significant cardiovascular disease, including any of the following within the past year:

    • Myocardial infarction
    • Unstable angina
    • Symptomatic congestive heart failure
    • Serious uncontrolled cardiac arrhythmia
  • No history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease)

PRIOR CONCURRENT THERAPY:

  • No prior pelvic radiotherapy
  • No metallic colon stent or rectal stent in situ
  • More than 30 days since prior chemotherapy, radiotherapy, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloproteinase inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibodies, or other experimental drugs
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT01263171


Locations
United Kingdom
Walsgrave Hospital
Coventry, England, United Kingdom, CV2 2DX
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Rosemere Cancer Centre at Royal Preston Hospital
Preston, England, United Kingdom, PR2 9HT
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
Glan Clwyd Hospital
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
Sponsors and Collaborators
Cardiff University
Cancer Research UK
Investigators
Principal Investigator: Simon Gollins, MD Glan Clwyd Hospital
  More Information

Responsible Party: Cardiff University
ClinicalTrials.gov Identifier: NCT01263171     History of Changes
Other Study ID Numbers: CDR0000691166
WCTU-COPERNICUS ( Other Identifier: Cardiff University )
2010-023083-40 ( EudraCT Number )
C23134/A11537 ( Other Grant/Funding Number: Cancer Research UK )
CARDIFF-SPON830-10 ( Other Identifier: Cardiff University )
First Submitted: December 17, 2010
First Posted: December 20, 2010
Last Update Posted: September 21, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Cardiff University:
adenocarcinoma of the rectum
stage IIIB rectal cancer
stage IIIC rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Fluorouracil
Levoleucovorin
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents