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 is currently recruiting participants.
Verified December 2012 by Wales Cancer Trials Unit
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
Wales Cancer Trials Unit
ClinicalTrials.gov Identifier:
NCT01263171
First received: December 17, 2010
Last updated: December 17, 2012
Last verified: December 2012
  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: L-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: 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

Resource links provided by NLM:


Further study details as provided by Wales Cancer Trials Unit:

Primary Outcome Measures:
  • Proportion of patients who commence neoadjuvant chemotherapy and radiotherapy and then undergo surgical resection [ Time Frame: Two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Feasibility in terms of achieved dose intensity for chemotherapy and radiotherapy [ Time Frame: Two years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Complete response [ Time Frame: Two years ] [ Designated as safety issue: No ]
  • Efficacy in terms of down-staging rectal cancer [ Time Frame: Two years ] [ Designated as safety issue: No ]
  • Local recurrence-free, distant metastasis-free, and overall survival at 1 year after surgery [ Time Frame: Two years ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: April 2012
Estimated Primary Completion Date: July 2014 (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: L-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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01263171

Locations
United Kingdom
Walsgrave Hospital Recruiting
Coventry, England, United Kingdom, CV2 2DX
Contact: Contact Person    44-24-7660-2020      
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Contact Person    44-113-206-6400      
Christie Hospital Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: Contact Person    44-845-226-3000      
Rosemere Cancer Centre at Royal Preston Hospital Recruiting
Preston, England, United Kingdom, PR2 9HT
Contact: Contact Person    44-1772-522-913      
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Contact Person    44-20-8642-6011      
Velindre Cancer Center at Velindre Hospital Recruiting
Cardiff, Wales, United Kingdom, CF14 2TL
Contact: Contact Person    44-29-2031-6292      
Glan Clwyd Hospital Recruiting
Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
Contact: Contact Person    44-1745-445-161    simon.gollins@cd-tr.wales.nhs.uk   
Sponsors and Collaborators
Wales Cancer Trials Unit
Cancer Research UK
Investigators
Principal Investigator: Simon Gollins, MD Glan Clwyd Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Wales Cancer Trials Unit
ClinicalTrials.gov Identifier: NCT01263171     History of Changes
Other Study ID Numbers: CDR0000691166, WCTU-COPERNICUS, EUDRACT-2010-023083-40, EU-21087, CRUK-C23134/A11537, CARDIFF-SPON830-10
Study First Received: December 17, 2010
Last Updated: December 17, 2012
Health Authority: Medicines and Healthcare products Regulatory Agency United Kingdom:

Keywords provided by Wales Cancer Trials Unit:
adenocarcinoma of the rectum
stage IIIB rectal cancer
stage IIIC rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on April 16, 2014