Rectal CancerPhase 2BRANCHNCT01481545
Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer
A Phase 2 study testing Radiation therapy, Oxaliplatin and Raltitrexed in people with Rectal Cancer, run by National Cancer Institute, Naples.
Trial summary
The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Radiation therapy, Oxaliplatin and Raltitrexed
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- No sites listed yet
- Study dates
- Dec 2006to Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with histologically or cytologically confirmed diagnosis of locally advanced rectal cancer (LARC) at high risk of recurrence (T4, N+, T3N0 with tumor located in the lower third of the rectum and/or circumferential resection margin (CRM) £5 mm), or LARC with resectable organ metastasis (M1).
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Life expectancy of at least 12 weeks
- Measurable and/or evaluable (resectable organ metastasis)lesions according to RECIST criteria
- Neutrophils > 1500 and Platelets > 100,000 /L
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- Total bilirubin < or = 1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) < or = 2.5 x UNL, or < or = 5 x UNL in case of liver metastases, alkaline phosphatase < or = 2.5 x UNL, or < or = 5 x UNL in case of liver metastases.
- Creatinine clearance > 50 mL/min or serum creatinine < or = 1.5 x UNL
- Urine dipstick of proteinuria < 2+. Patients discovered to have > or = 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate < or = 1 g of protein/24 hr.
- Written informed consent.
- Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating Center
Who cannot join
- Prior radiotherapy or chemotherapy for rectal cancer.
- Untreated brain metastases or spinal cord compression or primary brain tumours
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
- History of inflammatory bowel disease and/or acute/subacute bowel occlusion
- Serious, non-healing wound, ulcer, or bone fracture
- Evidence of bleeding diathesis or coagulopathy.
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- Uncontrolled hypertension
- Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
- Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
- Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration.
- Treatment with any investigational drug within 30 days prior to enrolment.
- Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications
- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
- Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
About this study
Official title: Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer: the BRANCH Trial
The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).
Read the detailed description
To determine the pathological complete response (pCR-TRG1) rate in patients treated with 2 different schedule of bevacizumab plus primary chemotherapy and radiotherapy of the pelvic region when optimal surgery is applied.
Bevacizumab will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage with the classical schedule Simon's methods will be used to calculate sample size.Setting a and b errors as 0.05 and 0.20, respectively, and defining as minimum activity of interest (p0) a TRG1 rate=30%. In order to demonstrate a TRG1 rate ≥50% (p1), at least 6 TRG1 on the first 15 patients, and at least 19 TRG1 on a total of 46 patients should be reported in the first and second stage, respectively.
- Conditions
- Rectal Cancer
- Being tested
- Radiation therapy, Oxaliplatin, Raltitrexed, levofolinic acid, 5-fluorouracil
- Keywords
- locally advanced, high risk, preoperative therapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation therapyRadiation
Radiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy
OxaliplatinDrug
100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)
RaltitrexedDrug
2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy)
levofolinic acidDrug
250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)
5-fluorouracilDrug
800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)
BevacizumabDrug
will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy)
| Study group | Role | What they receive |
|---|---|---|
| preoperative chemoradiotherapy | Experimental | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Receives: Radiation: Radiation therapy; Drug: Oxaliplatin; Drug: Raltitrexed; Drug: levofolinic acid; Drug: 5-fluorouracil; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Complete Tumor Regression Rate (TRG1)
Complete tumor regression rate (TRG1) was the ratio of patients with TRG1, graded at surgical resection, and total patients included in the study, expressed in percentage.
Tumor regression grade (TRG) was misured according to the Mandard Scale. Briefly,TRG1 was a complete tumor regression (regardless of the presence of acellular mucine lakes), and TRG2 was a nearly complete tumor regression with extensive fibrosis; TRG3 presented with clear evidence of residual cancer cells but with predominant fibrosis;TRG4 was a residual of cancer cells outgrowing fibrosis; TRG5 was the absence of regressive changes.
Measured: In 8 weeks after completion of chemoradiotherapy
Secondary outcomes (6)
Number of Participants With Adverse Events
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: Up to 8 weeks after surgery
Number of Patients With Sphincter Preservation
Sphincter preservation in patients with tumor < 5 cm from anal verge in 8 weeks after chemoradiation therapy
Measured: In 8 weeks after chemoradiation therapy
Progression Free Survival (PFS)
PFS was calculated from the date of the initial treatment until tumor progression or relapse, death for any cause or last follow up.
Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 10 years
Overall Survival (OS)
OS was calculated from the date of initial treatment to the date of death for any cause or last follow up.
Measured: 10 years
Clinical Response Rate
Clinical response was assessed before surgery with the same imaging modalities that were used for the inclusion in the study.
Clinical response rate was the ratio between complete and partial response, evaluated by RECIST CRITERIA, and total of patients evaluated, expressed in percentage of patients.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 7 weeks after chemoradiation therapy up to 11 weeks
Patients With Metastatic Lymphnodes at Pathology Exam After Surgery
Number of patients with metastatic lymphnodes at pathology exam after surgery.
Measured: In 8 weeks after chemoradiation therapy completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2011 (estimated)
- Study startDec 2006
- Primary completionJul 2011
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Naples
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonio Avallone, M.D., Principal investigator, National Cancer Institute, Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01481545
- Sponsor's protocol ID
- BRANCH
- Other IDs
- 2008-003989-26, 2008
- Acronym
- BRANCH
- Status last verified
- Sep 2020
- First submitted
- 11 Nov 2011
- Last updated
- 3 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer: the BRANCH Trial
- ClinicalTrials.gov ID
- NCT01481545
- Acronym / sponsor ID
- BRANCH / BRANCH
- Conditions
- Rectal Cancer
- Keywords
- locally advanced, high risk, preoperative therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Study start
- Dec 2006 (actual)
- Primary completion
- Jul 2011 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 29 Nov 2011 (estimated)
- Results
- Posted 3 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).
Detailed description
To determine the pathological complete response (pCR-TRG1) rate in patients treated with 2 different schedule of bevacizumab plus primary chemotherapy and radiotherapy of the pelvic region when optimal surgery is applied.
Bevacizumab will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage with the classical schedule Simon's methods will be used to calculate sample size.Setting a and b errors as 0.05 and 0.20, respectively, and defining as minimum activity of interest (p0) a TRG1 rate=30%. In order to demonstrate a TRG1 rate ≥50% (p1), at least 6 TRG1 on the first 15 patients, and at least 19 TRG1 on a total of 46 patients should be reported in the first and second stage, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| preoperative chemoradiotherapy | Experimental | Radiation: Radiation therapy, Drug: Oxaliplatin, Drug: Raltitrexed, Drug: levofolinic acid, Drug: 5-fluorouracil, Drug: BevacizumabPreoperative radiation therapy and combination chemotherapy plus bevacizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with histologically or cytologically confirmed diagnosis of locally advanced rectal cancer (LARC) at high risk of recurrence (T4, N+, T3N0 with tumor located in the lower third of the rectum and/or circumferential resection margin (CRM) £5 mm), or LARC with resectable organ metastasis (M1).
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Life expectancy of at least 12 weeks
- Measurable and/or evaluable (resectable organ metastasis)lesions according to RECIST criteria
Key exclusion criteria (15 listed)
- Prior radiotherapy or chemotherapy for rectal cancer.
- Untreated brain metastases or spinal cord compression or primary brain tumours
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
- History of inflammatory bowel disease and/or acute/subacute bowel occlusion
- Serious, non-healing wound, ulcer, or bone fracture
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 |
|---|---|---|
| Radiation therapyRadiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy | Radiation | preoperative chemoradiotherapy |
| Oxaliplatin100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy) | Drug | preoperative chemoradiotherapy |
| Raltitrexed2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy) | Drug | preoperative chemoradiotherapy |
| levofolinic acid250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy) | Drug | preoperative chemoradiotherapy |
| 5-fluorouracil800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy) | Drug | preoperative chemoradiotherapy |
| Bevacizumabwill be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy) | Drug | preoperative chemoradiotherapy |
Primary outcome
Percentage of Patients With Complete Tumor Regression Rate (TRG1)
Time frame: In 8 weeks after completion of chemoradiotherapy
Complete tumor regression rate (TRG1) was the ratio of patients with TRG1, graded at surgical resection, and total patients included in the study, expressed in percentage. Tumor regression grade (TRG) was misured according to the Mandard Scale. Briefly,TRG1 was a complete tumor regression (regardless of the presence of acellular mucine lakes), and TRG2 was a nearly complete tumor regression with extensive fibrosis; TRG3 presented with clear evidence of residual cancer cells but with predominant fibrosis;TRG4 was a residual of cancer cells outgrowing fibrosis; TRG5 was the absence of regressive changes.
6 secondary outcomes
Number of Participants With Adverse Events
Time frame: Up to 8 weeks after surgery
Number of Patients With Sphincter Preservation
Time frame: In 8 weeks after chemoradiation therapy
Progression Free Survival (PFS)
Time frame: 10 years
Overall Survival (OS)
Time frame: 10 years
Clinical Response Rate
Time frame: 7 weeks after chemoradiation therapy up to 11 weeks
Patients With Metastatic Lymphnodes at Pathology Exam After Surgery
Time frame: In 8 weeks after chemoradiation therapy completion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Antonio Avallone, M.D. principal investigator
National Cancer Institute, Naples
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation therapy, Oxaliplatin and Raltitrexed in people with Rectal Cancer, run by National Cancer Institute, Naples.
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 11 inclusion and 15 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 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 3 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Patients With Complete Tumor Regression Rate (TRG1) (time frame: In 8 weeks after completion of 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 3 Feb 2021.