Colorectal NeoplasmsPhase 3BRAZIL-TNTNCT05081687
Brazilian Total Neoadjuvant Therapy Trial
A Phase 3 study testing Folfirinox in people with Colorectal Neoplasms, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
Trial summary
Standard therapy for localized rectal cancer includes chemotherapy and radiation therapy, followed by a "recovery" period of 7-12 weeks, surgery and adjuvant chemotherapy for 3-6 months. Even though this protocol achieves high cure rates, many patients need a rectal amputation with placement of definitive colostomies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Folfirinox
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteBrazil
- Study dates
- 20 Feb 2020to 30 Dec 2023
- Phase
- Phase 3
- 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
- Age >= 18 y/o
- Biopsy-confirmed rectal adenocarcinoma
- Tumor Stage T3+ or N+ M0
- Adequate liver function (total bilirubin < = 4.0)
- Adequate kidney function (calculate creatinine-clearance >=30ml/m2/min)
- Adequate bone marrow function (Platelet counts >=90.000, hemoglobin >=8mg/dl, neutrophile count >= 1.500/cm3)
- Completed chemo-radiation with at least 54Gy and capecitabine 1650mg/m2/d
Who cannot join
- Prior tumor resection
- Prior radiation to the pelvis
- Prior chemotherapy for rectal cancer
- Life expectancy < 6 months
- Unfit for surgery
- Need for urgent/ immediate surgery
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital Municipal Vila Santa Catarina
São Paulo, 04378-500
Diogo Gomes, MD, +55-11-2151-8056, diogo.gomes@einstein.br
Leticia Brito, +55-11-2151-8056, leticia.brito@einstein.br
About this study
Official title: A Prospective Randomized Controlled Trial of Total Neo-adjuvant Therapy vs Conventional Chemo-radiation Aiming at Increasing Rates of Clinical Complete Response in Locally Advanced Rectal Cancer
Standard therapy for localized rectal cancer includes chemotherapy and radiation therapy, followed by a "recovery" period of 7-12 weeks, surgery and adjuvant chemotherapy for 3-6 months. Even though this protocol achieves high cure rates, many patients need a rectal amputation with placement of definitive colostomies. About 10-20% of patients have a complete clinical response to chemo-radiation and no tumor can be found in the surgical specimen. These patients can be followed with close surveillance and avid surgery. The aim of this study is to evaluate if a strategy including the use of a highly active chemotherapy called "FOLFIRINOX" during the 12 weeks between the end of radiation therapy and evaluation for surgery increases the rates of complete response and, therefore, allows more patients to undergo non-surgical management.
Read the detailed description
Adult patients with locally advanced rectal cancer who have completed conventional long-course chemo-radiation of 54Gy with capecitabine will be randomized 1:1 to a total neo-adjuvant therapy (TNT) protocol or to a control group. Patients in the TNT arm will receive 4 cycles of interval chemotherapy with FOLFIRINOX (5-FU, irinotecan, oxaliplatin) between the end of chemo-radiation and re-staging and those in the control group will undergo standard post-radiation care during this period. All patients will be re-staged with colonoscopy and pelvic MRI 12 weeks after the end of chemo-radiation. Those with a complete clinical response will be placed under a watch-and-wait protocol with digital rectal examinations every 2 months and pelvic MRI and sigmoidoscopy every 6 months. Those wih residual tumors will undergo resection with total mesorectal excision (TME). Patients with a "near complete response", as defined by a multidisciplinary tumor board, will be re-staged at week 16 or 18 after chemo-radiation before undergoing surgery. Adjuvant chemotherapy will be done following the local standard of care.
- Conditions
- Colorectal Neoplasms
- Being tested
- Folfirinox
- Keywords
- Rectal cancer, Neoadjuvant chemo-radiation, Total neoadjuvant therapy, Watch-and-wait
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FolfirinoxDrug
Also called mFOLFIRINOX, FOLFOXIRI, 5-FU, oxaliplatin, irinotecan
5-FU 2400mg/m2; Oxaliplatin 85 mg/m2, Irinotecan 150mg/m2
| Study group | Role | What they receive |
|---|---|---|
| Total neoadjuvant therapy (TNT) | Experimental | 4 cycles of mFOLFIRINOX every 14 days:
* Oxaliplatin 85 mg/m2
* Irinotecan 150mg/m2
* 5-FU 2.400mg/m2
* Dexamethasone 12mg
* Atropine 0.5mg
* Netupitant/palonosetron Receives: Drug: Folfirinox |
| Standard of care | No intervention | Standard post-radiation care |
What is being measured
The primary outcome is the main question the study is designed to answer.
cCR + PathCR
Complete clinical response or pathological response
Measured: 12 weeks after the end of chemoradiation
Secondary outcomes (3)
Rate of R0 resection
Rate of tumor resection with negative margins
Measured: 12 weeks
Rate of organ preservation
Rate of patients who remain colostomy-free
Measured: 6 months after surgery
Overall toxicity
Grade 3-4 toxicities according to CTCAE 4.0
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start20 Feb 2020
- Primary completion30 Nov 2023 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized 1:1 to one of two arms: TNT and conventional therapy (control). Randomization will be stratified by study site and tumor stage (II vs III)
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Brazil
- Responsible party
- Sponsor
- Investigators
- Diogo Gomes, MD, Principal investigator, Hospital Israelita Albert Einstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05081687
- Sponsor's protocol ID
- 4015-20
- Acronym
- BRAZIL-TNT
- Status last verified
- Oct 2022
- First submitted
- 5 Oct 2021
- Last updated
- 11 Oct 2023
- 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 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Controlled Trial of Total Neo-adjuvant Therapy vs Conventional Chemo-radiation Aiming at Increasing Rates of Clinical Complete Response in Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT05081687
- Acronym / sponsor ID
- BRAZIL-TNT / 4015-20
- Conditions
- Colorectal Neoplasms
- Keywords
- Rectal cancer, Neoadjuvant chemo-radiation, Total neoadjuvant therapy, Watch-and-wait
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Collaborators
- Ministry of Health, Brazil
- Study start
- 20 Feb 2020 (actual)
- Primary completion
- 30 Nov 2023 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 18 Oct 2021 (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.
Standard therapy for localized rectal cancer includes chemotherapy and radiation therapy, followed by a "recovery" period of 7-12 weeks, surgery and adjuvant chemotherapy for 3-6 months. Even though this protocol achieves high cure rates, many patients need a rectal amputation with placement of definitive colostomies. About 10-20% of patients have a complete clinical response to chemo-radiation and no tumor can be found in the surgical specimen. These patients can be followed with close surveillance and avid surgery. The aim of this study is to evaluate if a strategy including the use of a highly active chemotherapy called "FOLFIRINOX" during the 12 weeks between the end of radiation therapy and evaluation for surgery increases the rates of complete response and, therefore, allows more patients to undergo non-surgical management.
Detailed description
Adult patients with locally advanced rectal cancer who have completed conventional long-course chemo-radiation of 54Gy with capecitabine will be randomized 1:1 to a total neo-adjuvant therapy (TNT) protocol or to a control group. Patients in the TNT arm will receive 4 cycles of interval chemotherapy with FOLFIRINOX (5-FU, irinotecan, oxaliplatin) between the end of chemo-radiation and re-staging and those in the control group will undergo standard post-radiation care during this period. All patients will be re-staged with colonoscopy and pelvic MRI 12 weeks after the end of chemo-radiation. Those with a complete clinical response will be placed under a watch-and-wait protocol with digital rectal examinations every 2 months and pelvic MRI and sigmoidoscopy every 6 months. Those wih residual tumors will undergo resection with total mesorectal excision (TME). Patients with a "near complete response", as defined by a multidisciplinary tumor board, will be re-staged at week 16 or 18 after chemo-radiation before undergoing surgery. Adjuvant chemotherapy will be done following the local standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomized 1:1 to one of two arms: TNT and conventional therapy (control). Randomization will be stratified by study site and tumor stage (II vs III)
| Arm | Type | Receives |
|---|---|---|
| Total neoadjuvant therapy (TNT) | Experimental | Drug: Folfirinox4 cycles of mFOLFIRINOX every 14 days: * Oxaliplatin 85 mg/m2 * Irinotecan 150mg/m2 * 5-FU 2.400mg/m2 * Dexamethasone 12mg * Atropine 0.5mg * Netupitant/palonosetron |
| Standard of care | No intervention | –Standard post-radiation care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >= 18 y/o
- Biopsy-confirmed rectal adenocarcinoma
- Tumor Stage T3+ or N+ M0
- Adequate liver function (total bilirubin < = 4.0)
- Adequate kidney function (calculate creatinine-clearance >=30ml/m2/min)
Key exclusion criteria (6 listed)
- Prior tumor resection
- Prior radiation to the pelvis
- Prior chemotherapy for rectal cancer
- Life expectancy < 6 months
- Unfit for surgery
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 |
|---|---|---|
| FolfirinoxAlso: mFOLFIRINOX, FOLFOXIRI, 5-FU, oxaliplatin, irinotecan5-FU 2400mg/m2; Oxaliplatin 85 mg/m2, Irinotecan 150mg/m2 | Drug | Total neoadjuvant therapy (TNT) |
Primary outcome
cCR + PathCR
Time frame: 12 weeks after the end of chemoradiation
Complete clinical response or pathological response
3 secondary outcomes
Rate of R0 resection
Time frame: 12 weeks
Rate of organ preservation
Time frame: 6 months after surgery
Overall toxicity
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Program of the Brazilian Ministry of Health that us sponsoring the trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Colorectal Neoplasms
RecruitingPhase 1/2
A Clinical Study of MK-2870 Alone or With Other Treatments to Treat Gastrointestinal Cancers (MK-9999-02A)
Colorectal Cancer, Pancreatic Ductal Adenocarcinoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingObservational study
The French Gut-colo
Patients Aged 50-75 and Requiring Colonoscopy
RecruitingEarly Phase 1
Neuroprotective Potential of Cannabidiol (CBD) in Preventing Oxaliplatin (Ox)-Induced Neuropathy
Oxaliplatin Induced Peripheral Neuropathy in Cancer Patients, Metastatic Colorectal Cancer (CRC)
RecruitingPhase 1
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
Peritoneal Mesothelioma, Peritoneal Carcinomatosis
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.
Diogo Gomes, MD principal investigator
Hospital Israelita Albert Einstein
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Folfirinox in people with Colorectal Neoplasms, run by Hospital Israelita Albert Einstein 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 7 inclusion and 6 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 11 Oct 2023. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Diogo Gomes, MD (+55-11-2151-8056, diogo.gomes@einstein.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cCR + PathCR (time frame: 12 weeks after the end of chemoradiation). 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 11 Oct 2023.