Colorectal NeoplasmPhase 2NEOLARNCT03280407
NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer
A Phase 2 study testing Capecitabine, FOLFOX regimen (oxaliplatin/leucovorin/5FU) and CAPOX (oxaliplatin/capecitabine) in people with Colorectal Neoplasm and Colorectal Cancer, run by Zealand University Hospital at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasm, Colorectal Cancer, Rectal Neoplasms
- What is being tested?
- Capecitabine, FOLFOX regimen (oxaliplatin/leucovorin/5FU) and CAPOX (oxaliplatin/capecitabine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Mar 2017to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Lars Henrik Jensen, MD contact
Denmark1 site, 1 recruiting
- Recruiting
Vejle Hospital
Vejle
Lars Henrik Jensen, MD PhD, lars.henrik.jensen@rsyd.dk
About this study
Official title: NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial
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.
Read the 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.
- Conditions
- Colorectal Neoplasm, Colorectal Cancer, Rectal Neoplasms, Chemotherapy Effect, Intestinal Disease, Intestinal Neoplasms
- Being tested
- Capecitabine, FOLFOX regimen (oxaliplatin/leucovorin/5FU), CAPOX (oxaliplatin/capecitabine)
- Keywords
- Neoadjuvant chemotherapy,, locally advanced rectal cancer,, chemotherapy, CAPOX (oxaliplatin/capecitabine), FOLFOX (oxaliplatin/leucovorin/5FU)
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms, Intestinal Diseases, Intestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d
FOLFOX regimen (oxaliplatin/leucovorin/5FU)Drug
Also called FOLFOX (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.
CAPOX (oxaliplatin/capecitabine)Drug
Four cycles: Oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| A, capecitabine | Active comparator | Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy Receives: Drug: Capecitabine |
| B, FOLFOX or CAPOX | Experimental | Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice Receives: Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU); Drug: CAPOX (oxaliplatin/capecitabine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 5 years
Secondary outcomes (7)
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
Measured: 5 years
Local relapse
Defined to be within the pelvis. Any relapse should be verified by biopsy
Measured: 5 years
Distant relapse
Defined to be outside the pelvis. Any relapse should be verified by biopsy
Measured: 5 years
Early toxicity
Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.
Measured: 5 years
Late toxicity
Evaluated using CTCEA version 4.
Measured: 5 years
Functional outcome
Measured with LARS questionnaire
Measured: 5 years
Quality of life (QoL)
Measured with EORTC QoL questionnaire
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2017
- Study start1 Mar 2017
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ismail Gögenur, Zealand University Hospital
- Investigators
- Ismail Gögenur, MD, Study chair, Department of Surgery, ZUHLars Henrik Jensen, MD, Principal investigator, Vejle Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03280407
- Sponsor's protocol ID
- S-20160158
- Acronym
- NEOLAR
- Status last verified
- Sep 2017
- First submitted
- 7 Sep 2017
- Last updated
- 28 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer: a Randomized Phase II Trial
- ClinicalTrials.gov ID
- NCT03280407
- Acronym / sponsor ID
- NEOLAR / S-20160158
- Conditions
- Colorectal Neoplasm, Colorectal Cancer, Rectal Neoplasms, Chemotherapy Effect, Intestinal Disease, Intestinal Neoplasms
- Keywords
- Neoadjuvant chemotherapy,, locally advanced rectal cancer,, chemotherapy, CAPOX (oxaliplatin/capecitabine), FOLFOX (oxaliplatin/leucovorin/5FU)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 12 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| A, capecitabine | Active comparator | Drug: CapecitabineRadiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy |
| B, FOLFOX or CAPOX | Experimental | Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU), Drug: CAPOX (oxaliplatin/capecitabine)Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineRadio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d | Drug | A, capecitabine |
| FOLFOX regimen (oxaliplatin/leucovorin/5FU)Also: FOLFOX (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. | Drug | B, FOLFOX or CAPOX |
| 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. | Drug | B, FOLFOX or CAPOX |
Primary outcome
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)
7 secondary outcomes
Overall survival
Time frame: 5 years
Local relapse
Time frame: 5 years
Distant relapse
Time frame: 5 years
Early toxicity
Time frame: 5 years
Late toxicity
Time frame: 5 years
Functional outcome
Time frame: 5 years
Quality of life (QoL)
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2017.
- Individual participant dataSharing planned: Undecided. Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Henrik Jensen, MD contact
Ismail Gögenur, MD study chair
Department of Surgery, ZUH
Lars Henrik Jensen, MD principal investigator
Vejle Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine, FOLFOX regimen (oxaliplatin/leucovorin/5FU) and CAPOX (oxaliplatin/capecitabine) in people with Colorectal Neoplasm and Colorectal Cancer, run by Zealand University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ismail Gögenur, MD (+45 26336426, igo@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2017.