Locally Advanced Rectal CancerPhase 2AXEBEAMNCT00828672
Neoadjuvant Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin Locally Advanced Rectal Cancer
A Phase 2 study testing Oxaliplatin, Bevacizumab and Capecitabine in people with Locally Advanced Rectal Cancer, run by Universitaire Ziekenhuizen KU Leuven at 9 sites in Belgium.
Trial summary
Phase II clinical trial, open-label, randomized, two arms, multicentre (possibly multinational). Academic, investigator initiated. To assess the activity of bevacizumab (AvastinTM) in combination with capecitabine (XelodaTM) and radiation therapy with or without oxaliplatin (EloxatinTM) in the pre-operative treatment… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- Oxaliplatin, Bevacizumab and Capecitabine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 9 sitesBelgium
- Study dates
- Jun 2009to Mar 2019
- 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
- Adenocarcinoma of rectum measurable (RECIST), locally advanced (defined by MRI - Tumour beyond mesorectal fascia (T4) or Tumour ≤ 2 mm from mesorectal fascia or T3 tumour < 5 cm from anal verge
- Patient is at least 18 years of age
- Good organ function
Who cannot join
- Evidence of distant metastases
- Contraindication for bevacizumab
- Pregnant or breastfeeding women.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Belgium9 sites
Onze Lieve Vrouwziekenhuis
Aalst, 9300
ZNA Middelheim
Antwerp, ZNA Middelheim
AZ St- Lucas
Bruges, 8310
Erasme Hospital
Brussels, 1070
Cliniques Universitaires St Luc
Brussels, 1200
AZ Groeninge
Kortrijk, 8500
C.H.U. Sart-Tilman
Liège, 4000
Clinique Sainte Elisabeth
Namur, 5000
H. Hartziekenhuis
Roeselare, 8800
About this study
Official title: A Randomized Phase II Study of Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin in the Preoperative Treatment of Locally Advanced Rectal Cancer
Phase II clinical trial, open-label, randomized, two arms, multicentre (possibly multinational). Academic, investigator initiated.
To assess the activity of bevacizumab (AvastinTM) in combination with capecitabine (XelodaTM) and radiation therapy with or without oxaliplatin (EloxatinTM) in the pre-operative treatment of locally advanced rectal cancer, followed by TME (total mesorectal excision).
Read the detailed description
See Synopsis
- Conditions
- Locally Advanced Rectal Cancer
- Being tested
- Oxaliplatin, Bevacizumab, Capecitabine, radiotherapy
- Keywords
- bevacizumab, capecitabine, radiation therapy, oxaliplatin, multimodality treatments, TME (total mesorectal excision), Axe Beam, rectal cancer, neoadjuvant, pathological complete response, postoperative complications
- Medical subject headings
- Rectal Neoplasms, Postoperative Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Also called Eloxatin
Administered on days 15,22,29,36 en 43; 50 mg/m2
BevacizumabDrug
Also called Avastin
Administered on days 1,15,29 and 43 ; 5mg/kg
CapecitabineDrug
Also called Xeloda
825 mg/m2 ; 25 days - 5days per week, concurrent with radiotherapy
radiotherapyRadiation
Total dose 45Gy
| Study group | Role | What they receive |
|---|---|---|
| AXE (ARM 1) | Active comparator | Oxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy. Receives: Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Capecitabine; Radiation: radiotherapy |
| AX (ARM 2) | Active comparator | Bevacizumab and Capecitabine concurrently with radiotherapy Receives: Drug: Bevacizumab; Drug: Capecitabine; Radiation: radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Response at Surgery. Overview of Complete Pathologic Responses, Good and Little Tumour Regression Rates at Surgery.
Dworak tumour regression grades (TRG) were used to assess pathologic response: TRG0=no regression. TRG1=dominant tumor mass with obvious fibrosis and/or vasculopathy; TRG2=dominant fibrotic changes with few tumour cells or groups; TRG3=very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucus substance. TRG4=no intact viable tumour cells, only fibrotic mass or presence of mucin lakes without associated malignant cells (total tumour regression). Pathologic assessments of tumour response post chemoradiotherapy as provided by investigators (read by local pathologists on operative specimens) were reviewed centrally for all pts for whom surgical materials were available (centrally reviewed set). The diagnosis of independent central reviewers primed. Pathologic complete response rates (TRG4) are reported (%). Good (TRG3 and TRG4 together) and little (TRG 0,1 and 2) tumour regression rates are summarized. For these 2 last rows, % add to 100.
Measured: 4 months
Secondary outcomes (6)
Number of Participants With Histopathologic R0 and Negative CRM Resection
Histopathologic R0 resection rate was defined as margins histologically negative for tumour involvement after resection. The circumferential resection margin (CRM) is considered to be involved if microscopic tumour is present <1mm from or at the inked circumferential or radial resection margin. Data on quality of mesorectal excision were expected but not collected consistently.
Measured: 4 months
Number of Participants With Pathologic Complete Response at Surgery. Number of Participants With Good or Little Pathological Tumour Regression at Surgery.
Dworak tumour regression grades (TRG) were used to assess pathologic response: TRG0=no regression. TRG1=dominant tumor mass with obvious fibrosis and/or vasculopathy; TRG2=dominant fibrotic changes with few tumour cells or groups; TRG3=very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucus substance. TRG4=no intact viable tumour cells, only fibrotic mass or presence of mucin lakes without associated malignant cells (total tumour regression). Pathologic assessments of tumour response post chemoradiotherapy as provided by investigators (read by local pathologists on operative specimens) were reviewed centrally for all pts for whom surgical materials were available (centrally reviewed set). The diagnosis of independent central reviewers primed. Pathologic complete response rates (TRG4) are reported (%). Good (TRG3 and TRG4 together) and little (TRG 0,1 and 2) tumour regression rates are summarized. For these 2 last rows, % add to 100.
Measured: 4 months
Clinical Response Rate
Baseline tumour measurements were performed within 4 weeks prior to treatment start (RECIST). The same methods of assessment (CT and/or MRI) were used for each measurable lesion at baseline and during follow-up.
- Complete Response (CR) is disappearance of all clinical and radiological evidence of tumour (both target and non-target lesions).
- Partial Response (PR) is at least a 30% decrease in the sum of LD of target lesions, taking as reference the baseline sum of tumour longest diameters (LD).
- Stable Disease (SD) is steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
- Progressive Disease (PD) is at least a 20% increase in the sum of LD of measured lesions taking as references the smallest sum LD recorded since the treatment started. Appearance of new lesions constitutes PD. In exceptional circumstances, unequivocal progression of non-target lesions was considered evidence of PD.
Measured: 3 months
Types and Numbers of Adverse Events - General Overview
Adverse events graded as per NCI CTCAE (US National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. All Serious Adverse Events occurrences are reported and counts are summarized here; all Adverse Events (all grades) related and not related to study treatment are reported and summarized here; all severe laboratory events (hematology and biochemistry Gr 3 and higher) are reported and summarized here; all severe postoperative complications (Gr 3 and higher) occurred within the first month post surgery are reported and summarized here. See section Adverse events for details.
Measured: continuous up to 1 year
Recurrence Rates and Disease Free Survival
Counts and proportions of patients experiencing recurrence of disease (local and distant).
Measured: up to 5 years
Death Rates and Overall Survival
Counts and proportions of patients deceased (post-study).
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2009 (estimated)
- Study startJun 2009
- Primary completionMar 2014
- Study completionMar 2019
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 Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric Van Cutsem, Prof. Dr., Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00828672
- Sponsor's protocol ID
- s51104 - ML5194
- Other IDs
- 2007-007177-23, MO19051
- Acronym
- AXEBEAM
- Status last verified
- Jul 2019
- First submitted
- 23 Jan 2009
- Last updated
- 10 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin in the Preoperative Treatment of Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT00828672
- Acronym / sponsor ID
- AXEBEAM / s51104 - ML5194
- Conditions
- Locally Advanced Rectal Cancer
- Keywords
- bevacizumab, capecitabine, radiation therapy, oxaliplatin, multimodality treatments, TME (total mesorectal excision), Axe Beam, rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- Jun 2009 (actual)
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 26 Jan 2009 (estimated)
- Results
- Posted 10 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase II clinical trial, open-label, randomized, two arms, multicentre (possibly multinational). Academic, investigator initiated.
To assess the activity of bevacizumab (AvastinTM) in combination with capecitabine (XelodaTM) and radiation therapy with or without oxaliplatin (EloxatinTM) in the pre-operative treatment of locally advanced rectal cancer, followed by TME (total mesorectal excision).
Detailed description
See Synopsis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AXE (ARM 1) | Active comparator | Drug: Oxaliplatin, Drug: Bevacizumab, Drug: Capecitabine, Radiation: radiotherapyOxaliplatin, Bevacizumab and Capecitabine concurrently with radiotherapy. |
| AX (ARM 2) | Active comparator | Drug: Bevacizumab, Drug: Capecitabine, Radiation: radiotherapyBevacizumab and Capecitabine concurrently with radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adenocarcinoma of rectum measurable (RECIST), locally advanced (defined by MRI - Tumour beyond mesorectal fascia (T4) or Tumour ≤ 2 mm from mesorectal fascia or T3 tumour < 5 cm from anal verge
- Patient is at least 18 years of age
- Good organ function
Key exclusion criteria (3 listed)
- Evidence of distant metastases
- Contraindication for bevacizumab
- Pregnant or breastfeeding women.
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 |
|---|---|---|
| OxaliplatinAlso: EloxatinAdministered on days 15,22,29,36 en 43; 50 mg/m2 | Drug | AXE (ARM 1) |
| BevacizumabAlso: AvastinAdministered on days 1,15,29 and 43 ; 5mg/kg | Drug | AX (ARM 2), AXE (ARM 1) |
| CapecitabineAlso: Xeloda825 mg/m2 ; 25 days - 5days per week, concurrent with radiotherapy | Drug | AX (ARM 2), AXE (ARM 1) |
| radiotherapyTotal dose 45Gy | Radiation | AX (ARM 2), AXE (ARM 1) |
Primary outcome
Pathologic Response at Surgery. Overview of Complete Pathologic Responses, Good and Little Tumour Regression Rates at Surgery.
Time frame: 4 months
Dworak tumour regression grades (TRG) were used to assess pathologic response: TRG0=no regression. TRG1=dominant tumor mass with obvious fibrosis and/or vasculopathy; TRG2=dominant fibrotic changes with few tumour cells or groups; TRG3=very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucus substance. TRG4=no intact viable tumour cells, only fibrotic mass or presence of mucin lakes without associated malignant cells (total tumour regression). Pathologic assessments of tumour response post chemoradiotherapy as provided by investigators (read by local pathologists on operative specimens) were reviewed centrally for all pts for whom surgical materials were available (centrally reviewed set). The diagnosis of independent central reviewers primed. Pathologic complete response rates (TRG4) are reported (%). Good (TRG3 and TRG4 together) and little (TRG 0,1 and 2) tumour regression rates are summarized. For these 2 last rows, % add to 100.
6 secondary outcomes
Number of Participants With Histopathologic R0 and Negative CRM Resection
Time frame: 4 months
Number of Participants With Pathologic Complete Response at Surgery. Number of Participants With Good or Little Pathological Tumour Regression at Surgery.
Time frame: 4 months
Clinical Response Rate
Time frame: 3 months
Types and Numbers of Adverse Events - General Overview
Time frame: continuous up to 1 year
Recurrence Rates and Disease Free Survival
Time frame: up to 5 years
Death Rates and Overall Survival
Time frame: up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Eric Van Cutsem, Prof. Dr. principal investigator
UZ Leuven
9 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 Oxaliplatin, Bevacizumab and Capecitabine in people with Locally Advanced Rectal Cancer, run by Universitaire Ziekenhuizen KU Leuven at 9 sites in Belgium.
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 3 inclusion and 3 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 10 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Belgium. 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?
Yes. Results are posted in the registry (first posted 10 Jul 2019). 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?
Pathologic Response at Surgery. Overview of Complete Pathologic Responses, Good and Little Tumour Regression Rates at Surgery. (time frame: 4 months). 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 10 Jul 2019.