Rectal Cancer, AdenocarcinomaPhase 2ICARNCT03170115
Induction Chemotherapy Plus Chemoradiotherapy With or Without Aspirin in High Risk Rectal Cancer
A Phase 2 study testing Aspirin in people with Rectal Cancer, Adenocarcinoma and Locally Advanced Malignant Neoplasm, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.
Trial summary
The benefit of aspirin in cancer of the colon and rectum is already known. Recently, it was described its potential activity during chemoradiotherapy, with higher rate of tumor downstaging. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer, Adenocarcinoma, Locally Advanced Malignant Neoplasm, Chemoradiation
- What is being tested?
- Aspirin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteBrazil
- Study dates
- 30 Nov 2017to 17 Jan 2020
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed adenocarcinoma of mid or low rectum
- Locally advanced rectal cancer with one of the high-risk factors confirmed by high-resolution thin-slice Magnetic resonance image (3 mm)
- tumors extending to within 1 mm of, or beyond the mesorectal fascia;
- tumor extending 5 mm or more into perirectal fat;
- resectable cT4 tumors;
- lower third;
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- nodal involvement;
- extramural vascular invasion
- ECOG performance status of 0-2
- An informed consent has been signed by the patient
Who cannot join
- Upper rectal cancer
- Metastatic disease
- The patient received any previous therapy for colorectal cancer or another malignancy
- Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
- Previous thromboembolic or haemorrhagic events within 6 months prior to registration
- Patients with malabsorption syndrome or difficulties in swallowing
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- The patient has severe underlying diseases or poor condition to receive chemotherapy or radiotherapy
- Pregnant of breastfeeding women
- The patient who participate in another clinical trial, or receives any drug for the trial
- Uncontrolled peripheral neuropathy (more than grade 2)
- Active gastrointestinal bleeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Randomized Study of Induction Chemotherapy Followed by Chemoradiotherapy With or Without Aspirin in High Risk Locally Advanced Rectal Cancer
The benefit of aspirin in cancer of the colon and rectum is already known. Recently, it was described its potential activity during chemoradiotherapy, with higher rate of tumor downstaging. Furthermore, induction chemotherapy followed by chemoradiation represents an attractive approach, with more favorable compliance and toxicity profiles. The aim of this study was to evaluate the efficacy of total neoadjuvant treatment and assess the efficacy and feasibility of aspirin use during chemoradiotherapy for high-risk rectal cancer.
Read the detailed description
Methods: This is a randomized trial to evaluate induction treatment with XELOX and Capecitabine-based chemoradiotherapy with or without aspirin in a high-risk population selected by MRI. High-risk will be defined by presence of at least one of the following criteria on high-resolution thin-slice MRI (3 mm): tumors extending to within 1 mm of, or beyond the mesorectal fascia; tumor extending 5 mm or more into perirectal fat; resectable cT4 tumors; lower third; nodal involvement; extramural vascular invasion. Random assignment of treatment will be stratified by MRI tumour regression grade. All the patients enrolled in the study will receive XELOX every 21 days for four cycles, unless unacceptable toxicity or progression is detected. After this treatment, patients will be randomized to receive Capecitabine-based chemoradiotherapy with aspirin or placebo (Capecitabine 850 mg/m² 5 days per week combined with radiotherapy with total dose of 50.4 Gy in 28 days). After 8-10 weeks, they will be evaluate by MRI. Patients with incomplete clinical response will be referred to immediate surgery and patients with complete clinical response will be managed with "watch and wait" approach. Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.
The sample size was calculated according to Simon's optimal two-stage design. Accordingly, 11 patients must be included in each group during the first stage and 20 during the second stage. A treatment regimen will be considered effective if more than 18 patients of the total 31 show downstaging (final analysis), reaching 80% power with an alpha of 0.05 level of significance.
- Being tested
- Aspirin, Placebo Oral Tablet
- Keywords
- Rectal Cancer, Total neoadjuvant therapy, Induction chemotherapy, Aspirin colorectal cancer
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called aas
chemoradiotherapy with capecitabine and aspirin Aspirin daily during chemoradiotherapy
Placebo Oral TabletDrug
Also called placebo
chemoradiotherapy with capecitabine and placebo Placebo daily during chemoradiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Aspirin | Experimental | Induction chemotherapy followed by chemoradiotherapy with aspirin Aspirin 100mg daily during the chemoradiotherapy Receives: Drug: Aspirin |
| Placebo Oral Tablet | Placebo comparator | Induction chemotherapy followed by chemoradiotherapy without aspirin Placebo daily during the chemoradiotherapy Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor downstaging after induction chemotherapy followed by chemoradiotherapy with or without aspirin
This will be assessed by MR imaging 8-10 weeks after chemoradiotherapy and it will be considered tumor downstaging if mrTRG 1 to 3
Measured: 8-10 weeks after chemoradiotherapy
Secondary outcomes (5)
Radiological Tumor response rate after induction chemotherapy
This will be assessed by MR imaging after induction chemotherapy
Measured: 3-4 weeks after last induction chemotherapy
Pathological Tumor response rate
Amount of tumor regression after surgery according to the guideline including Mandard
Measured: 10-12 weeks after chemoradiotherapy
Pathologic complete response
it will be defined as the absence of residual invasive cancer on pathological evaluation of the complete resected rectal specimen
Measured: 8-10 weeks after chemoradiotherapy
Disease-free survival
defined as the time from surgery to relapse or death, whichever occurred first
Measured: 3 years
Overall survival
defined as the time from surgery to death, whichever occurred first
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 posted30 May 2017
- Study start30 Nov 2017
- Primary completion17 Jan 2020
- Study completion17 Jan 2020
Why it stopped: Aspirin added to chemoradiotherapy was safe but did not improve response to total neoadjuvant treatment. The study was closed due absence of benefit.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal Cancer, AdenocarcinomaStudies 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
- preoperative induction chemotherapy followed by combined radiochemotherapy with capecitabine and aspirin
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cancer, Brazil
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Luiz Henrique Araujo, MD, PHD, Principal investigator, National Cancer Institute, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03170115
- Sponsor's protocol ID
- ICAR trial
- Acronym
- ICAR
- Status last verified
- Dec 2020
- First submitted
- 17 Apr 2017
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Study of Induction Chemotherapy Followed by Chemoradiotherapy With or Without Aspirin in High Risk Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT03170115
- Acronym / sponsor ID
- ICAR / ICAR trial
- Keywords
- Rectal Cancer, Total neoadjuvant therapy, Induction chemotherapy, Aspirin colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Aspirin added to chemoradiotherapy was safe but did not improve response to total neoadjuvant treatment. The study was closed due absence of benefit.
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Instituto Nacional de Cancer, BrazilOther government
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 17 Jan 2020 (actual)
- Study completion
- 17 Jan 2020 (actual)
- First posted
- 30 May 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 benefit of aspirin in cancer of the colon and rectum is already known. Recently, it was described its potential activity during chemoradiotherapy, with higher rate of tumor downstaging. Furthermore, induction chemotherapy followed by chemoradiation represents an attractive approach, with more favorable compliance and toxicity profiles. The aim of this study was to evaluate the efficacy of total neoadjuvant treatment and assess the efficacy and feasibility of aspirin use during chemoradiotherapy for high-risk rectal cancer.
Detailed description
Methods: This is a randomized trial to evaluate induction treatment with XELOX and Capecitabine-based chemoradiotherapy with or without aspirin in a high-risk population selected by MRI. High-risk will be defined by presence of at least one of the following criteria on high-resolution thin-slice MRI (3 mm): tumors extending to within 1 mm of, or beyond the mesorectal fascia; tumor extending 5 mm or more into perirectal fat; resectable cT4 tumors; lower third; nodal involvement; extramural vascular invasion. Random assignment of treatment will be stratified by MRI tumour regression grade. All the patients enrolled in the study will receive XELOX every 21 days for four cycles, unless unacceptable toxicity or progression is detected. After this treatment, patients will be randomized to receive Capecitabine-based chemoradiotherapy with aspirin or placebo (Capecitabine 850 mg/m² 5 days per week combined with radiotherapy with total dose of 50.4 Gy in 28 days). After 8-10 weeks, they will be evaluate by MRI. Patients with incomplete clinical response will be referred to immediate surgery and patients with complete clinical response will be managed with "watch and wait" approach. Patients with progression disease during the treatment phase will be withdrawn from the study and will receive their treatment according to the investigator's judgment.
The sample size was calculated according to Simon's optimal two-stage design. Accordingly, 11 patients must be included in each group during the first stage and 20 during the second stage. A treatment regimen will be considered effective if more than 18 patients of the total 31 show downstaging (final analysis), reaching 80% power with an alpha of 0.05 level of significance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- preoperative induction chemotherapy followed by combined radiochemotherapy with capecitabine and aspirin
| Arm | Type | Receives |
|---|---|---|
| Aspirin | Experimental | Drug: AspirinInduction chemotherapy followed by chemoradiotherapy with aspirin Aspirin 100mg daily during the chemoradiotherapy |
| Placebo Oral Tablet | Placebo comparator | Drug: Placebo Oral TabletInduction chemotherapy followed by chemoradiotherapy without aspirin Placebo daily during the chemoradiotherapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed adenocarcinoma of mid or low rectum
- Locally advanced rectal cancer with one of the high-risk factors confirmed by high-resolution thin-slice Magnetic resonance image (3 mm)
- ECOG performance status of 0-2
- An informed consent has been signed by the patient
Key exclusion criteria (11 listed)
- Upper rectal cancer
- Metastatic disease
- The patient received any previous therapy for colorectal cancer or another malignancy
- Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
- Previous thromboembolic or haemorrhagic events within 6 months prior to registration
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 |
|---|---|---|
| AspirinAlso: aaschemoradiotherapy with capecitabine and aspirin Aspirin daily during chemoradiotherapy | Drug | Aspirin |
| Placebo Oral TabletAlso: placebochemoradiotherapy with capecitabine and placebo Placebo daily during chemoradiotherapy | Drug | Placebo Oral Tablet |
Primary outcome
Tumor downstaging after induction chemotherapy followed by chemoradiotherapy with or without aspirin
Time frame: 8-10 weeks after chemoradiotherapy
This will be assessed by MR imaging 8-10 weeks after chemoradiotherapy and it will be considered tumor downstaging if mrTRG 1 to 3
5 secondary outcomes
Radiological Tumor response rate after induction chemotherapy
Time frame: 3-4 weeks after last induction chemotherapy
Pathological Tumor response rate
Time frame: 10-12 weeks after chemoradiotherapy
Pathologic complete response
Time frame: 8-10 weeks after chemoradiotherapy
Disease-free survival
Time frame: 3 years
Overall survival
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Aspirin added to chemoradiotherapy was safe but did not improve response to total neoadjuvant treatment. The study was closed due absence of benefit.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Individual participant dataSharing planned: No
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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.
Luiz Henrique Araujo, MD, PHD principal investigator
National Cancer Institute, France
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 Aspirin in people with Rectal Cancer, Adenocarcinoma and Locally Advanced Malignant Neoplasm, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.
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 10 inclusion and 11 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: stopped early, as of the sponsor's last update on 17 Dec 2020. 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 Brazil. 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. Some participants in this study may receive a placebo. 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?
The study was stopped early (reason given: Aspirin added to chemoradiotherapy was safe but did not improve response to total neoadjuvant treatment. The study was closed due absence of benefit.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor downstaging after induction chemotherapy followed by chemoradiotherapy with or without aspirin (time frame: 8-10 weeks after chemoradiotherapy). 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 17 Dec 2020; AzTrials last refreshed its copy on 6 Nov 2026.