Rectal CancerPhase 2TRUSTNCT03085992
Folfoxiri Plus Bevacizumab Followed by Chemoradiotherapy Plus Bevacizumab in Patients With Resectable Rectal Cancer
A Phase 2 study testing FOLFOXIRI plus Bevacizumab and Chemoradiotherapy plus Bevacizumab in people with Rectal Cancer, run by Azienda Ospedaliero, Universitaria Pisana at 4 sites in Italy.
Trial summary
This study includes patients affected by advanced and resectable rectal adenocarcinoma. It provides an induction chemotherapy with FOLFOXIRI regimen plus Bevacizumab followed by Chemoradiotherapy plus Bevacizumab. Surgery with total mesorectal incision must be performed within 7-9 weeks after this last treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- FOLFOXIRI plus Bevacizumab and Chemoradiotherapy plus Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 4 sitesItaly
- Study dates
- Mar 2012to 12 Mar 2018
- 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 proven diagnosis of rectal adenocarcinoma. Diagnosis obtained by a biopsy technique which leaves the major portion of the tumor intact.
- Locally advanced, resectable disease defined by the presence of at least one of the following features: tumour extending to within 1 mm of or beyond the mesorectal fascia (ie, circumferential radial margin threatened or involved); lower third (≤ 6 cm from the anal verge) cT3 tumours; tumour extending 5 mm or more into perirectal fat; T4 tumour (ie, invading surrounding structures or peritoneum); clinical stage III disease (T1-4, N1-2), with the definition of a clinically positive lymph node being any node ≥ 1.0 cm;
- Distal border of the tumor must be located < 12 cm from the anal verge.
- No evidence of metastatic disease by CT scan of the chest and abdomen and total body PET-CT scan.
- Tumor must be amenable to curative resection (curative resection can include pelvic exenteration).
- No history of invasive rectal malignancy, regardless of disease-free interval.
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- No other rectal cancers (i.e., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, or cloacogenic carcinoma) or synchronous colon cancer.
- No clear indication of involvement of the pelvic side walls by imaging.
- Age between 18 and 75 years.
- ECOG Performance status < 2 if age < 70 years and = 0 if age 71-75 years.
- Life expectancy of at least 5 years (excluding diagnosis of cancer).
- Hematopoietic: absolute neutrophil count ≥ 1,000/mm3; platelet count ≥ 100,000/mm3; haemoglobin level ≥ 10 g/dL.
- Hepatic: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase ≤ 2 times ULN; AST ≤ 2 times ULN. [Note: *If AST>ULN, serologic testing for Hepatitis B and C must be negative].
- Renal: creatinine clearance > 50 mL/min; no renal disease that would preclude study treatment or follow-up.
- Written informed consent to experimental treatment and pharmacogenomic analyses.
Who cannot join
- Previous treatment with oxaliplatin, irinotecan or bevacizumab. Previous 5-fluorouracil or capecitabine treatment is allowed.
- Previous pelvic radiation therapy.
- Hepatic disease that would preclude study treatment or follow-up; uncontrolled coagulopathy; history of viral hepatitis or other chronic liver disease.
- Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; active ischemic heart disease; myocardial infarction within the past 6 months; symptomatic arrhythmia; uncontrolled hypertension.
- Lack of upper gastrointestinal tract integrity or malabsorption syndrome; active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic).
- Pregnant or lactating women. Fertile patients must use effective contraception (i.e double-barrier contraceptive measures, oral contraception or avoidance of intercourse during the study and for 30 days after surgery).
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- Patients with prior malignancies (with the exception of rectal cancer), including invasive colon cancer, are eligible provided they have been disease-free for ≥ 5 years and are deemed by their physician to be at low risk for recurrence.
- Other malignancy within the past 5 years with the exception of effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum.
- Known hypersensitivity to fluorouracil, oxaliplatin or irinotecan or to Chinese hamster ovary cell proteins.
- Clinically significant peripheral neuropathy (i.e., neurosensory or neuromotor toxicity ≥ grade 2).
- Psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Irccs Istituto Oncologico Veneto
Padova, 35128
Polo Oncologico Area Vasta Nord Ovest
Pisa, 56100
ausl5 di Pisa
Pontedera, 56100
Dipartimento Oncologico AUSL 7
Siena, 53100
About this study
Official title: Open-label Phase II Study of Induction Treatment With Folfoxiri Plus Bevacizumab Followed by Preoperative Chemoradiotherapy Plus Bevacizumab in Patients With Locally Advanced, Resectable Rectal Cancer.
This study includes patients affected by advanced and resectable rectal adenocarcinoma. It provides an induction chemotherapy with FOLFOXIRI regimen plus Bevacizumab followed by Chemoradiotherapy plus Bevacizumab. Surgery with total mesorectal incision must be performed within 7-9 weeks after this last treatment. The protocol will be evaluate the disease free survival at two years. Translational analyses will be performed to show the presence of VEGF polymorphism, CD133 surface markers on colorectal CSCs.
- Conditions
- Rectal Cancer
- Being tested
- FOLFOXIRI plus Bevacizumab, Chemoradiotherapy plus Bevacizumab
- Keywords
- rectal cancer, FOLFOXIRI, bevacizumab, trust
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOXIRI plus BevacizumabDrug
- BEVACIZUMAB 5 mg/kg over 30 minutes, day 1
- IRINOTECAN 165 mg/sqm IV over 1-h, day 1
- OXALIPLATIN 85 mg/sqm IV over 2-h, day 1
- L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1
- 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1 administered every two weeks for 6 cycles (3 months).
Chemoradiotherapy plus BevacizumabOther
- FLUOROURACIL 225 mg/sqm/day by protracted IV continuous infusion or -CAPECITABINE 825 mg/sqm/bid p.o. continuously without interruption for all the duration of radiation treatment;
- EXTERNAL-BEAM IRRADIATION 50.4 GY in 28 daily fractions over 5.5 weeks;
- BEVACIZUMAB 5 mg/kg over 30 minutes, starting on day 1 of radiation treatment day 1 and then every two weeks (for 3 cycles).
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | INDUCTION TREATMENT WITH FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY PREOPERATIVE CHEMORADIOTHERAPY PLUS BEVACIZUMAB Receives: Drug: FOLFOXIRI plus Bevacizumab; Other: Chemoradiotherapy plus Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival rate at 2 years
Disease-free survival is defined as time from study entry until progression of disease (according to RECIST 1.1) or death from any cause. Patients who are alive without having progressed at the end of the study will be censored at their last radiological assessment.
Measured: Up to 2 years
Secondary outcomes (4)
Response rate
Response rate is defined as the fraction of treated patients who achieve a response as defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria vers. 1.1.
Measured: Up to 2 years
Toxicity Rate
Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing treatment-related adverse events as assessed by National Cancer Institute Common Toxicity Criteria (version 3.0), during induction and concomitant chemoradiotherapy
Measured: Up to 2 years
Overall survival
Overall survival is defined as the time from study entry until death from any cause. Patients who are alive at the end of the study will be censored at that point.
Measured: Up to 2 years
Pathological complete response rate
Pathological complete response rate is defined as the fraction of treated patients who achieve pathological response after treatment
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2017
- Study startMar 2012
- Primary completionJul 2017
- Study completion12 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero, Universitaria Pisana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alfredo Falcone, Azienda Ospedaliero, Universitaria Pisana
- Investigators
- Alfredo Falcone, MD, Principal investigator, Polo Oncologico Area Vasta Nord Ovest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03085992
- Sponsor's protocol ID
- TRUST
- Other IDs
- 2011-003340-45
- Acronym
- TRUST
- Status last verified
- Mar 2018
- First submitted
- 8 Jun 2016
- Last updated
- 14 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Phase II Study of Induction Treatment With Folfoxiri Plus Bevacizumab Followed by Preoperative Chemoradiotherapy Plus Bevacizumab in Patients With Locally Advanced, Resectable Rectal Cancer.
- ClinicalTrials.gov ID
- NCT03085992
- Acronym / sponsor ID
- TRUST / TRUST
- Conditions
- Rectal Cancer
- Keywords
- rectal cancer, FOLFOXIRI, bevacizumab, trust
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Azienda Ospedaliero, Universitaria PisanaUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Jul 2017 (actual)
- Study completion
- 12 Mar 2018 (actual)
- First posted
- 22 Mar 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.
This study includes patients affected by advanced and resectable rectal adenocarcinoma. It provides an induction chemotherapy with FOLFOXIRI regimen plus Bevacizumab followed by Chemoradiotherapy plus Bevacizumab. Surgery with total mesorectal incision must be performed within 7-9 weeks after this last treatment. The protocol will be evaluate the disease free survival at two years. Translational analyses will be performed to show the presence of VEGF polymorphism, CD133 surface markers on colorectal CSCs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: FOLFOXIRI plus Bevacizumab, Other: Chemoradiotherapy plus BevacizumabINDUCTION TREATMENT WITH FOLFOXIRI PLUS BEVACIZUMAB FOLLOWED BY PREOPERATIVE CHEMORADIOTHERAPY PLUS BEVACIZUMAB |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically proven diagnosis of rectal adenocarcinoma. Diagnosis obtained by a biopsy technique which leaves the major portion of the tumor intact.
- Locally advanced, resectable disease defined by the presence of at least one of the following features: tumour extending to within 1 mm of or beyond the mesorectal fascia (ie, circumferential radial margin threatened or involved); lower third (≤ 6 cm from the anal verge) cT3 tumours; tumour extending 5 mm or more into perirectal fat; T4 tumour (ie, invading surrounding structures or peritoneum); clinical stage III disease (T1-4, N1-2), with the definition of a clinically positive lymph node being any node ≥ 1.0 cm;
- Distal border of the tumor must be located < 12 cm from the anal verge.
- No evidence of metastatic disease by CT scan of the chest and abdomen and total body PET-CT scan.
- Tumor must be amenable to curative resection (curative resection can include pelvic exenteration).
Key exclusion criteria (11 listed)
- Previous treatment with oxaliplatin, irinotecan or bevacizumab. Previous 5-fluorouracil or capecitabine treatment is allowed.
- Previous pelvic radiation therapy.
- Hepatic disease that would preclude study treatment or follow-up; uncontrolled coagulopathy; history of viral hepatitis or other chronic liver disease.
- Cardiovascular disease that would preclude study treatment or follow-up; New York Heart Association class III or IV heart disease; active ischemic heart disease; myocardial infarction within the past 6 months; symptomatic arrhythmia; uncontrolled hypertension.
- Lack of upper gastrointestinal tract integrity or malabsorption syndrome; active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic).
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 |
|---|---|---|
| FOLFOXIRI plus Bevacizumab* BEVACIZUMAB 5 mg/kg over 30 minutes, day 1 * IRINOTECAN 165 mg/sqm IV over 1-h, day 1 * OXALIPLATIN 85 mg/sqm IV over 2-h, day 1 * L-LEUCOVORIN 200 mg/sqm IV over 2-h, day 1 * 5-FLUOROURACIL 3200 mg/sqm IV 48-h continuous infusion, starting on day 1 administered every two weeks for 6 cycles (3 months). | Drug | Single Arm |
| Chemoradiotherapy plus Bevacizumab* FLUOROURACIL 225 mg/sqm/day by protracted IV continuous infusion or -CAPECITABINE 825 mg/sqm/bid p.o. continuously without interruption for all the duration of radiation treatment; * EXTERNAL-BEAM IRRADIATION 50.4 GY in 28 daily fractions over 5.5 weeks; * BEVACIZUMAB 5 mg/kg over 30 minutes, starting on day 1 of radiation treatment day 1 and then every two weeks (for 3 cycles). | Other | Single Arm |
Primary outcome
Disease-free survival rate at 2 years
Time frame: Up to 2 years
Disease-free survival is defined as time from study entry until progression of disease (according to RECIST 1.1) or death from any cause. Patients who are alive without having progressed at the end of the study will be censored at their last radiological assessment.
4 secondary outcomes
Response rate
Time frame: Up to 2 years
Toxicity Rate
Time frame: Up to 2 years
Overall survival
Time frame: Up to 2 years
Pathological complete response rate
Time frame: Up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2018.
- Individual participant dataSharing planned: 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.
Alfredo Falcone, MD principal investigator
Polo Oncologico Area Vasta Nord Ovest
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FOLFOXIRI plus Bevacizumab and Chemoradiotherapy plus Bevacizumab in people with Rectal Cancer, run by Azienda Ospedaliero, Universitaria Pisana at 4 sites in Italy.
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 15 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: finished, as of the sponsor's last update on 14 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Disease-free survival rate at 2 years (time frame: Up to 2 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 14 Mar 2018.