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NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer (NEOLAR)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03280407
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : September 28, 2017
Sponsor:
Information provided by (Responsible Party):
Ismail Gögenur, Zealand University Hospital

Tracking Information
First Submitted Date  ICMJE September 7, 2017
First Posted Date  ICMJE September 12, 2017
Last Update Posted Date September 28, 2017
Actual Study Start Date  ICMJE March 1, 2017
Estimated Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
Disease free survival [ Time Frame: 5 years ]
All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually until the number of events is reached and the trial is stopped (max 5 years)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • Overall survival [ Time Frame: 5 years ]
    All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years
  • Local relapse [ Time Frame: 5 years ]
    Defined to be within the pelvis. Any relapse should be verified by biopsy
  • Distant relapse [ Time Frame: 5 years ]
    Defined to be outside the pelvis. Any relapse should be verified by biopsy
  • Early toxicity [ Time Frame: 5 years ]
    Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.
  • Late toxicity [ Time Frame: 5 years ]
    Evaluated using CTCEA version 4.
  • Functional outcome [ Time Frame: 5 years ]
    Measured with LARS questionnaire
  • Quality of life (QoL) [ Time Frame: 5 years ]
    Measured with EORTC QoL questionnaire
Original Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
  • Overall survival [ Time Frame: 5 years ]
    All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years
  • Local relapse [ Time Frame: 5 years ]
    Defined to be within the pelvis. Any relapse should be verified by biopsy
  • Distant relapse [ Time Frame: 5 years ]
    Defined to be outside the pelvis. Any relapse should be verified by biopsy
  • Early toxicity [ Time Frame: 5 years ]
    Evaluated using CTCEA version 4.
  • Late toxicity [ Time Frame: 5 years ]
    Evaluated using CTCEA version 4.
  • Functional outcome [ Time Frame: 5 years ]
    Measured with LARS questionnaire
  • QoL [ Time Frame: 5 years ]
    Measured with EORTC QoL questionnaire
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer
Official Title  ICMJE NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial
Brief Summary

The main clinical hypothesis is that compared to radio-chemotherapy for low and mid rectal tumors or surgery for high rectal tumors neoadjuvant chemotherapy reduces the rate of distant relapse without increasing the rate of local relapse.

The aim of the present study is to compare long term and short term outcomes in rectal cancer patients undergoing standard treatment (radio-chemotherapy/surgery) or experimental neoadjuvant chemotherapy/surgery Furthermore, early surgical and medical complications, the functional outcome, toxicity and quality of life (QoL) may be improved if radiotherapy can be avoided.

Exploratory analyses are planned in order to find potential predictive markers for selecting patients to either radio-chemotherapy/surgery or neoadjuvant combination chemotherapy/surgery.

Detailed Description The standard treatment of locally advanced but resectable cancer in the middle or lower rectum is preoperative radio-chemotherapy and in the upper part initial surgery. The clinical benefit from radio-chemotherapy is primarily through a reduction in local relapse but the treatment is associated with acute toxicity and long term functional dysfunction. Subsequently, it is important to select patients with high risk of local relapse. Intense systemic combination chemotherapy reduces the risk of distant relapse and increases survival in the postoperative setting. The biological rationale is eradication of micrometastases and hence it may be anticipated that earlier, i.e. neoadjuvant, combination therapy may improve systemic control.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is an open label, randomized phase II screening trial allocating eligible patients to either standard treatment for rectal cancer or experimental preoperative combination chemotherapy.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colorectal Neoplasm
  • Colorectal Cancer
  • Rectal Neoplasms
  • Chemotherapy Effect
  • Intestinal Disease
  • Intestinal Neoplasms
  • Rectal Cancer
Intervention  ICMJE
  • Drug: Capecitabine
    Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d
  • Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU)
    Six cycles: Oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every two weeks.
    Other Name: FOLFOX (oxaliplatin/leucovorin/5FU)
  • Drug: CAPOX (oxaliplatin/capecitabine)
    Four cycles: Oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.
Study Arms  ICMJE
  • Active Comparator: A, capecitabine
    Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy
    Intervention: Drug: Capecitabine
  • Experimental: B, FOLFOX or CAPOX
    Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
    Interventions:
    • Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU)
    • Drug: CAPOX (oxaliplatin/capecitabine)
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 8, 2017)
124
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adenocarcinoma of the rectum with the lower boarder within 15 cm from the anal verge
  • Locally advanced tumor based on imaging
  • T3 tumors within 10 cm from the anal verge fulfilling the criteria for preoperative radio-chemotherapy according to Danish Colorectal Cancer Group (DCCG) guidelines
  • T3c or T4 tumors 10-15 cm from the anal verge
  • Deemed resectable at the multidisciplinary team (MDT) conference
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Age at least 18 years
  • Adequate bone marrow, liver and renal function allowing systemic chemotherapy
  • Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l.
  • Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value
  • Calculated or measured renal glomerular filtration rate at least 30 mL/min
  • Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable
  • Written and orally informed consent

Exclusion Criteria:

  • Distant metastasis
  • Invasive ingrowth into other organs
  • Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
  • Previous radiotherapy to the pelvis
  • Previous treatment with 5FU or oxaliplatin
  • Surgery within two weeks
  • Neuropathy NCI grade > 1
  • Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
  • Pregnant (positive pregnancy test) or breast feeding women
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: Ismail Gögenur, MD +45 26336426 igo@regionsjaelland.dk
Contact: Lars Henrik Jensen, MD
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03280407
Other Study ID Numbers  ICMJE S-20160158
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Undecided
Responsible Party Ismail Gögenur, Zealand University Hospital
Study Sponsor  ICMJE Zealand University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Ismail Gögenur, MD Department of Surgery, ZUH
Principal Investigator: Lars Henrik Jensen, MD Vejle Hospital
PRS Account Zealand University Hospital
Verification Date September 2017

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