Back to resultsNEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer (NEOLAR)
Primary Purpose
Colorectal Neoplasm, Colorectal Cancer, Rectal Neoplasms
Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Capecitabine
FOLFOX regimen (oxaliplatin/leucovorin/5FU)
CAPOX (oxaliplatin/capecitabine)
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasm focused on measuring Neoadjuvant chemotherapy,, locally advanced rectal cancer,, chemotherapy, CAPOX (oxaliplatin/capecitabine), FOLFOX (oxaliplatin/leucovorin/5FU)
Eligibility Criteria
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
Sites / Locations
- Vejle HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
A, capecitabine
B, FOLFOX or CAPOX
Arm Description
Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy
Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
Outcomes
Primary Outcome Measures
Disease free survival
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
Overall survival
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
Defined to be within the pelvis. Any relapse should be verified by biopsy
Distant relapse
Defined to be outside the pelvis. Any relapse should be verified by biopsy
Early toxicity
Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.
Late toxicity
Evaluated using CTCEA version 4.
Functional outcome
Measured with LARS questionnaire
Quality of life (QoL)
Measured with EORTC QoL questionnaire
Full Information
NCT ID
NCT03280407
First Posted
September 7, 2017
Last Updated
September 26, 2017
Sponsor
Zealand University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03280407
Brief Title
NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer
Acronym
NEOLAR
Official Title
NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
December 31, 2018 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zealand University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasm, Colorectal Cancer, Rectal Neoplasms, Chemotherapy Effect, Intestinal Disease, Intestinal Neoplasms, Rectal Cancer
Keywords
Neoadjuvant chemotherapy,, locally advanced rectal cancer,, chemotherapy, CAPOX (oxaliplatin/capecitabine), FOLFOX (oxaliplatin/leucovorin/5FU)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
124 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A, capecitabine
Arm Type
Active Comparator
Arm Description
Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy
Arm Title
B, FOLFOX or CAPOX
Arm Type
Experimental
Arm Description
Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d
Intervention Type
Drug
Intervention Name(s)
FOLFOX regimen (oxaliplatin/leucovorin/5FU)
Other Intervention Name(s)
FOLFOX (oxaliplatin/leucovorin/5FU)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
CAPOX (oxaliplatin/capecitabine)
Intervention Description
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 Measure Information:
Title
Disease free survival
Description
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)
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years
Time Frame
5 years
Title
Local relapse
Description
Defined to be within the pelvis. Any relapse should be verified by biopsy
Time Frame
5 years
Title
Distant relapse
Description
Defined to be outside the pelvis. Any relapse should be verified by biopsy
Time Frame
5 years
Title
Early toxicity
Description
Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.
Time Frame
5 years
Title
Late toxicity
Description
Evaluated using CTCEA version 4.
Time Frame
5 years
Title
Functional outcome
Description
Measured with LARS questionnaire
Time Frame
5 years
Title
Quality of life (QoL)
Description
Measured with EORTC QoL questionnaire
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ismail Gögenur, MD
Phone
+45 26336426
Email
igo@regionsjaelland.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Lars Henrik Jensen, MD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ismail Gögenur, MD
Organizational Affiliation
Department of Surgery, ZUH
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lars Henrik Jensen, MD
Organizational Affiliation
Vejle Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vejle Hospital
City
Vejle
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars Henrik Jensen, MD PhD
Email
lars.henrik.jensen@rsyd.dk
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Undecided
Learn more about this trial
NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer
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