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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. Identifier: NCT03280407
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : September 28, 2017
Information provided by (Responsible Party):
Ismail Gögenur, Zealand University Hospital

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.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasm Colorectal Cancer Rectal Neoplasms Chemotherapy Effect Intestinal Disease Intestinal Neoplasms Rectal Cancer Drug: Capecitabine Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU) Drug: CAPOX (oxaliplatin/capecitabine) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
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
Official Title: NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: A, capecitabine
Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy
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

Experimental: B, FOLFOX or CAPOX
Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
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.

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. 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

  2. Local relapse [ Time Frame: 5 years ]
    Defined to be within the pelvis. Any relapse should be verified by biopsy

  3. Distant relapse [ Time Frame: 5 years ]
    Defined to be outside the pelvis. Any relapse should be verified by biopsy

  4. Early toxicity [ Time Frame: 5 years ]
    Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.

  5. Late toxicity [ Time Frame: 5 years ]
    Evaluated using CTCEA version 4.

  6. Functional outcome [ Time Frame: 5 years ]
    Measured with LARS questionnaire

  7. Quality of life (QoL) [ Time Frame: 5 years ]
    Measured with EORTC QoL questionnaire

Information from the National Library of Medicine

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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:

  • 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

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): NCT03280407

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Contact: Ismail Gögenur, MD +45 26336426
Contact: Lars Henrik Jensen, MD

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Vejle Hospital Recruiting
Vejle, Denmark
Contact: Lars Henrik Jensen, MD PhD   
Sponsors and Collaborators
Zealand University Hospital
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Study Chair: Ismail Gögenur, MD Department of Surgery, ZUH
Principal Investigator: Lars Henrik Jensen, MD Vejle Hospital
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Responsible Party: Ismail Gögenur, Professor, Zealand University Hospital Identifier: NCT03280407    
Other Study ID Numbers: S-20160158
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ismail Gögenur, Zealand University Hospital:
Neoadjuvant chemotherapy,
locally advanced rectal cancer,
CAPOX (oxaliplatin/capecitabine)
FOLFOX (oxaliplatin/leucovorin/5FU)
Additional relevant MeSH terms:
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Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Intestinal Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Growth Substances