Colorectal CancerPhase 2NCT01227707
A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.
A Phase 2 study testing bevacizumab [Avastin], capecitabine [Xeloda] and Radiation therapy in people with Colorectal Cancer, run by Hoffmann-La Roche at 9 sites in Italy.
Trial summary
This open-label study will assess the efficacy and safety of Avastin (bevacizumab) plus Xeloda (capecitabine) in combination with standard technique radiotherapy of the pelvic region in the neo-adjuvant setting in patients with locally advanced primary rectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- bevacizumab [Avastin], capecitabine [Xeloda] and Radiation therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 9 sitesItaly
- Study dates
- Nov 2005to Aug 2010
- 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
- Adult patients, >=18 years of age
- Patients with confirmed rectal cancer who are subject to surgery and would benefit from pre-operative combined chemo-radiotherapy
- Measurable and/or evaluable lesions according to RECIST criteria
- EOCG performance status 0-1
Who cannot join
- Prior radiotherapy or chemotherapy for rectal cancer
- Untreated brain metastases or spinal cord compression or primary brain tumors
- Chronic daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
- Co-existing malignancies, or malignancies diagnosed within the last 5 years, with the exception of basal and squamous cell cancer, or cervical cancer in situ.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Italy9 sites
Study site
Ancona, 60121
Study site
Bologna, 40139
Study site
Cuneo, 12100
Study site
Genova, 16132
Study site
Naples, 80131
Study site
Paola, 87027
Study site
Pisa, 56100
Study site
Roma, 00135
Study site
Siena, 53100
About this study
Official title: An Open-label Study to Assess the Effect of Combination Treatment With Avastin and Xeloda, Plus Pre-operative Standard Radiotherapy, on Response Rate in Patients With Locally Advanced Rectal Cancer.
This open-label study will assess the efficacy and safety of Avastin (bevacizumab) plus Xeloda (capecitabine) in combination with standard technique radiotherapy of the pelvic region in the neo-adjuvant setting in patients with locally advanced primary rectal cancer. Patients will receive 4 courses of Avastin at a dose of 5 mg/kg intravenously (iv) every 2 weeks and for 38 days Xeloda at dose of 825 mg/kg twice daily orally, plus radiation therapy. After surgery, adjuvant treatment with 5-fluorouracil/leucovorin and, at the discretion of the investigator, with Avastin 5 mg/kg iv every 2 weeks for at least 6 months will be given.
- Conditions
- Colorectal Cancer
- Being tested
- bevacizumab [Avastin], capecitabine [Xeloda], Radiation therapy, Mesorectal excision, 5-fluorouracil
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumab [Avastin]Drug
5 mg/kg intravenously every 2 weeks, 4 cycles
capecitabine [Xeloda]Drug
825 mg/m2 twice daily orally, 38 days
Radiation therapyRadiation
Total dose of 45 Gy over 38 days
Mesorectal excisionProcedure or surgery
6-8 weeks after completion of neoadjuvant treatment
bevacizumab [Avastin]Drug
Post-surgery adjuvant treatment at the discretion of the investigator: 5 mg/kg iv every 2 weeks for at least 6 months
5-fluorouracilDrug
Post-surgery adjuvant therapy: bolus of 400mg/m2 iv plus iv infusion of 600 mg/m2 on Days 1 and 2 of each 2-week cycle for 6 months
leucovorinDrug
Post-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Not described Receives: Drug: bevacizumab [Avastin]; Drug: capecitabine [Xeloda]; Radiation: Radiation therapy; Procedure: Mesorectal excision; Drug: 5-fluorouracil; Drug: leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Pathological Complete Response (pCR)
pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.
Measured: 6 to 8 weeks following completion of neoadjuvant treatment
Secondary outcomes (12)
Percentage of Participants by Primary Tumor (T), Regional Lymph Nodes (N), and Distant Metastasis (M) Clinical Stage at Baseline and at the End of Neo-Adjuvant Treatment (NAT)
The frequencies of clinical tumor stage T (0, 1, 2, 3, 4, or X), regional lymph nodes stage N (0, 1, 2, 3, or 4), and distant metastasis clinical stage M (0, 1, or X) at baseline and at the end of NAT were assessed. The frequencies of pathological tumor stage T and regional lymph nodes stage N at surgery were evaluated. The clinical tumor and lymph node status was assessed by clinical examination, endosonography, and/or rectosigmoidoscopy, and pelvic and abdomen computerized tomography (CT) scan or magnetic resonance imaging (MRI). Response to treatment had to be assessed within 6 weeks after end of treatment by using the same techniques performed at baseline.
Measured: Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment)
Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure
Measured: 6 to 8 weeks after completion of study treatment
Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment
Percentage of participants with CR was evaluated as the proportion of participants with complete response for the target and non-target lesions, separately, at the end of NAT according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions or all non-target lesions and normalization of tumor marker levels.
Measured: BL and within 6 weeks after the completion of study treatment
Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment
Percentage of participants with an overall response of CR was evaluated as the proportion of participants with CR for the target and non-target lesions plus absence of new lesions at the end of NAT according to RECIST. CR was defined as disappearance of all target lesions, all non-target lesions, and normalization of tumor marker levels.
Measured: BL and within 6 weeks after the completion of study treatment
Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment
The percentage of participants with new lesions located at the primary tumor site were evaluated at the end of NAT.
Measured: BL and within 6 weeks after the completion of study treatment
Percentage of Participants With Relapse During Follow-Up
The percentage of participants with local and/or regional relapse during follow-up. New lesions located at rectum or at colon or at lymph node detected at the end of NAT were evaluated as local and/or regional relapse.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months
Disease-Free Survival (DFS) - Percentage of Participants With an Event
DFS was defined as the time from treatment start date to the date of first progression of disease or date of death due to any cause.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months
DFS - Time to Event
The time in months from date of start-of-treatment to the date of event defined as the first documented disease progression or death due to any cause. If a participant did not have an event, the time was censored at the date of last adequate tumor assessment. DFS was estimated using the Kaplan-Meier method.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months
Overall Survival (OS) - Percentage of Participants With an Event
OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
OS - Time to Event
OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive. OS was estimated using the Kaplan-Meier method.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
Time to Disease Progression (TTP) - Percentage of Participants With an Event
TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
TTP - Time to Event
TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer. TTP was estimated using the Kaplan-Meier method.
Measured: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study startNov 2005
- Primary completionAug 2010
- Study completionAug 2010
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 Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01227707
- Sponsor's protocol ID
- ML18522
- Status last verified
- Jul 2015
- First submitted
- 22 Oct 2010
- Last updated
- 17 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Assess the Effect of Combination Treatment With Avastin and Xeloda, Plus Pre-operative Standard Radiotherapy, on Response Rate in Patients With Locally Advanced Rectal Cancer.
- ClinicalTrials.gov ID
- NCT01227707
- Acronym / sponsor ID
- ML18522
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Nov 2005
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 25 Oct 2010 (estimated)
- Results
- Posted 15 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label study will assess the efficacy and safety of Avastin (bevacizumab) plus Xeloda (capecitabine) in combination with standard technique radiotherapy of the pelvic region in the neo-adjuvant setting in patients with locally advanced primary rectal cancer. Patients will receive 4 courses of Avastin at a dose of 5 mg/kg intravenously (iv) every 2 weeks and for 38 days Xeloda at dose of 825 mg/kg twice daily orally, plus radiation therapy. After surgery, adjuvant treatment with 5-fluorouracil/leucovorin and, at the discretion of the investigator, with Avastin 5 mg/kg iv every 2 weeks for at least 6 months will be given.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: bevacizumab [Avastin], Drug: capecitabine [Xeloda], Radiation: Radiation therapy, Procedure: Mesorectal excision, Drug: 5-fluorouracil, Drug: leucovorin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients, >=18 years of age
- Patients with confirmed rectal cancer who are subject to surgery and would benefit from pre-operative combined chemo-radiotherapy
- Measurable and/or evaluable lesions according to RECIST criteria
- EOCG performance status 0-1
Key exclusion criteria (4 listed)
- Prior radiotherapy or chemotherapy for rectal cancer
- Untreated brain metastases or spinal cord compression or primary brain tumors
- Chronic daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
- Co-existing malignancies, or malignancies diagnosed within the last 5 years, with the exception of basal and squamous cell cancer, or cervical cancer in situ.
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 |
|---|---|---|
| bevacizumab [Avastin]5 mg/kg intravenously every 2 weeks, 4 cycles | Drug | Single Arm |
| capecitabine [Xeloda]825 mg/m2 twice daily orally, 38 days | Drug | Single Arm |
| Radiation therapyTotal dose of 45 Gy over 38 days | Radiation | Single Arm |
| Mesorectal excision6-8 weeks after completion of neoadjuvant treatment | Procedure or surgery | Single Arm |
| bevacizumab [Avastin]Post-surgery adjuvant treatment at the discretion of the investigator: 5 mg/kg iv every 2 weeks for at least 6 months | Drug | Single Arm |
| 5-fluorouracilPost-surgery adjuvant therapy: bolus of 400mg/m2 iv plus iv infusion of 600 mg/m2 on Days 1 and 2 of each 2-week cycle for 6 months | Drug | Single Arm |
| leucovorinPost-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months | Drug | Single Arm |
Primary outcome
Percentage of Participants With Pathological Complete Response (pCR)
Time frame: 6 to 8 weeks following completion of neoadjuvant treatment
pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.
12 secondary outcomes
Percentage of Participants by Primary Tumor (T), Regional Lymph Nodes (N), and Distant Metastasis (M) Clinical Stage at Baseline and at the End of Neo-Adjuvant Treatment (NAT)
Time frame: Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment)
Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure
Time frame: 6 to 8 weeks after completion of study treatment
Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment
Time frame: BL and within 6 weeks after the completion of study treatment
Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment
Time frame: BL and within 6 weeks after the completion of study treatment
Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment
Time frame: BL and within 6 weeks after the completion of study treatment
Percentage of Participants With Relapse During Follow-Up
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months
Disease-Free Survival (DFS) - Percentage of Participants With an Event
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months
DFS - Time to Event
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months
Overall Survival (OS) - Percentage of Participants With an Event
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
OS - Time to Event
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
Time to Disease Progression (TTP) - Percentage of Participants With an Event
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
TTP - Time to Event
Time frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2015.
- 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.
Clinical Trials study chair
Hoffmann-La Roche
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 bevacizumab [Avastin], capecitabine [Xeloda] and Radiation therapy in people with Colorectal Cancer, run by Hoffmann-La Roche at 9 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 4 inclusion and 4 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 17 Aug 2015. 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 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?
Yes. Results are posted in the registry (first posted 15 Aug 2014). 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 Participants With Pathological Complete Response (pCR) (time frame: 6 to 8 weeks following completion of neoadjuvant treatment). 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 Aug 2015.