Colorectal CancerPhase 3OBELICSNCT01718873
Optimization of Bevacizumab Scheduling With Chemotherapy for Metastatic Colorectal Cancer
A Phase 3 study testing Bevacizumab, Oxaliplatin and levo-folinic acid in people with Colorectal Cancer, run by National Cancer Institute, Naples at 1 site in Italy.
Trial summary
The purpose of this study is to evaluate if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Bevacizumab, Oxaliplatin and levo-folinic acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 1 siteItaly
- Study dates
- May 2012to Dec 2019
- Phase
- Phase 3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological diagnosis of colorectal adenoma carcinoma
- Stage IV disease
- Presence of at least one measurable target lesion (according to RECIST), and not previously radiated.
- Age ≥ 18 e ≤ 75 years
- ECOG Performance status 0-1
- Life expectancy >3 months
Show all 9Show fewer
- Adequate recovery from surgery, with at least 28 days from surgery to date of pre-study biopsy.
- Adequate contraception for male and female patients of child bearing potential
- informed consent
Who cannot join
- More than one previous line of therapy for metastatic disease
- Prior treatment with bevacizumab or oxaliplatin (previous treatment with irinotecan,, cetuximab, fluoropyrimidine, folic acid are permitted)
- Primary tumor that is stenosing and/or that infiltrates the entire thickness of the intestinal wall
- Regular use of NSAIDs or aspirin
- Bleeding disorders or coagulopathy
- Concurrent anticoagulant therapy
Show all 19Show fewer
- Suspected or cerebral metastases (to verify in the presence of symptoms)
- Neutrophils < 2000 / mm3, platelets < 100,000 / mm3, hemoglobin < 9g/dl
- Creatinine > 1.5 times the upper normal limit
- GOT and/or GPT > 2.5 times the upper normal limit, bilirubin > 1.5 times the upper normal limit in absence of liver metastases
- GOT and/or GPT > 5 times the upper normal limit, bilirubin > 3 times the upper normal limit in presence of liver metastases
- 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
- Congestive heart failure, ischemic coronary events within past 12 months, uncontrolled cardiac arrhythmia
- Uncontrolled hypertension
- Active or uncontrolled infection
- Any concomitant condition that, in the investigator's opinion, would contraindicate the use of any of the study drugs
- Pregnancy or lactation
- Central nervous system disorders or peripheral neuropathy > grade 1 (CTCAE v. 4.0)
- Inability to comply with follow up procedures of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer
The purpose of this study is to evaluate if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment.
Read the detailed description
OBELICS is a two-arm phase 3 trial comparing in mCRC patients (1:1): concurrent administration of bevacizumab in combination with modified FOLFOX-6 regimen (mFOLFOX-6) or modified OXXEL regimen (mOXXEL), in which bevacizumab is administered the same day as oxaliplatin, (standard arm); and sequential administration of bevacizumab with the same chemotherapeutic regimens, in which bevacizumab is administered 4 days before oxaliplatin at each cycle (experimental arm) Oxaliplatin regimen (mFOLFOX/mOXXEL) is chosen according to local clinical practice at the beginning of the study.
- Conditions
- Colorectal Cancer
- Being tested
- Bevacizumab, Oxaliplatin, levo-folinic acid, 5-fluorouracil, Capecitabine
- Keywords
- metastatic, stage IV
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
5 mg/kg every 2 weeks for up to 24 weeks. After 24 weeks, those patients without disease progression will receive bevacizumab 7.5 mg/kg every 3 weeks until progression of disease or unacceptable toxicity.
OxaliplatinDrug
Also called Eloxatin
85mg/m2 IV every 2 weeks for up to 24 weeks
levo-folinic acidDrug
Also called Lederfolin
200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks
5-fluorouracilDrug
Also called Fluorouracil
400 mg/m2 IV bolus followed by 2400 mg/m2 IV infusion over 46 hours, every 2 weeks for up to 24 weeks (given in mFOLFOX-6 schedule)
CapecitabineDrug
Also called Xeloda
1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule)
| Study group | Role | What they receive |
|---|---|---|
| bevacizumab before chemotherapy | Experimental | Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Receives: Drug: Bevacizumab; Drug: Oxaliplatin; Drug: levo-folinic acid; Drug: 5-fluorouracil; Drug: Capecitabine |
| bevacizumab with chemotherapy | Active comparator | Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Receives: Drug: Bevacizumab; Drug: Oxaliplatin; Drug: levo-folinic acid; Drug: 5-fluorouracil; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, was the primary end point and was defined as the number of complete plus partial responses divided by the number of enrolled patients.
Per RECIST v 1.1 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: Objective response was assessed by computed tomographic scan or other appropriate imaging at weeks 12 and 24 from randomization, and every 3 months thereafter, assessed up to 90 months.
Secondary outcomes (4)
Disease Control Rate
Disease control rate was calculated by adding complete and partial responses and stable disease.
Measured: At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months
Overall Survival
Overall survival was defined as the time from randomization to the date of death. Patients alive at the time of the final analysis were censored on the date of the last follow-up information available.
Measured: assessed up to 90 months
Progression-free Survival (PFS)
Progression-free survival was defined as the time from randomization to the date of progression or death, whichever occurred first. Patients without progression were censored on the date of the last follow-up visit.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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: assessed up to 90 months
Toxic Effects
Toxic effects were scored according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. For the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 scale score range from 1 to 4. A high score, that is 3 and 4, represents a high level of toxicity, whereas the minimum values, that is 1 and 2, represents a mild/modest level of toxicity.
Measured: up to 4 weeks after the end of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2012 (estimated)
- Study startMay 2012
- Primary completionDec 2015
- Study completionDec 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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 230 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
- NCT01718873
- Sponsor's protocol ID
- OBELICS
- Other IDs
- 2011-004997-27
- Acronym
- OBELICS
- Status last verified
- Oct 2021
- First submitted
- 29 Oct 2012
- Last updated
- 12 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Avallone A, Piccirillo MC, Nasti G, Rosati G, Carlomagno C, Di Gennaro E, Romano C, Tatangelo F, Granata V, Cassata A, Silvestro L, De Stefano A, Aloj L, Vicario V, Nappi A, Leone A, Bilancia D, Arenare L, Petrillo A, Lastoria S, Gallo C, Botti G, Delrio P, Izzo F, Perrone F, Budillon A. Effect of Bevacizumab in Combination With Standard Oxaliplatin-Based Regimens in Patients With Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jul 1;4(7):e2118475. doi: 10.1001/jamanetworkopen.2021.18475.
PubMed 34309665Avallone A, Piccirillo MC, Aloj L, Nasti G, Delrio P, Izzo F, Di Gennaro E, Tatangelo F, Granata V, Cavalcanti E, Maiolino P, Bianco F, Aprea P, De Bellis M, Pecori B, Rosati G, Carlomagno C, Bertolini A, Gallo C, Romano C, Leone A, Caraco C, de Lutio di Castelguidone E, Daniele G, Catalano O, Botti G, Petrillo A, Romano GM, Iaffaioli VR, Lastoria S, Perrone F, Budillon A. A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme). BMC Cancer. 2016 Feb 8;16:69. doi: 10.1186/s12885-016-2102-y.
PubMed 26857924
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 3 Study on the Optimization of Bevacizumab With mFOLFOX/mOXXEL in the Treatment of Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01718873
- Acronym / sponsor ID
- OBELICS / OBELICS
- Conditions
- Colorectal Cancer
- Keywords
- metastatic, stage IV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Study start
- May 2012 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 31 Oct 2012 (estimated)
- Results
- Posted 12 Apr 2023
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 if giving bevacizumab prior to chemotherapy compared to giving bevacizumab at the same time as chemotherapy improves patient overall response to treatment.
Detailed description
OBELICS is a two-arm phase 3 trial comparing in mCRC patients (1:1): concurrent administration of bevacizumab in combination with modified FOLFOX-6 regimen (mFOLFOX-6) or modified OXXEL regimen (mOXXEL), in which bevacizumab is administered the same day as oxaliplatin, (standard arm); and sequential administration of bevacizumab with the same chemotherapeutic regimens, in which bevacizumab is administered 4 days before oxaliplatin at each cycle (experimental arm) Oxaliplatin regimen (mFOLFOX/mOXXEL) is chosen according to local clinical practice at the beginning of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| bevacizumab before chemotherapy | Experimental | Drug: Bevacizumab, Drug: Oxaliplatin, Drug: levo-folinic acid, Drug: 5-fluorouracil, Drug: CapecitabineBevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) |
| bevacizumab with chemotherapy | Active comparator | Drug: Bevacizumab, Drug: Oxaliplatin, Drug: levo-folinic acid, Drug: 5-fluorouracil, Drug: CapecitabineBevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histological diagnosis of colorectal adenoma carcinoma
- Stage IV disease
- Presence of at least one measurable target lesion (according to RECIST), and not previously radiated.
- Age ≥ 18 e ≤ 75 years
- ECOG Performance status 0-1
Key exclusion criteria (19 listed)
- More than one previous line of therapy for metastatic disease
- Prior treatment with bevacizumab or oxaliplatin (previous treatment with irinotecan,, cetuximab, fluoropyrimidine, folic acid are permitted)
- Primary tumor that is stenosing and/or that infiltrates the entire thickness of the intestinal wall
- Regular use of NSAIDs or aspirin
- Bleeding disorders or coagulopathy
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 |
|---|---|---|
| BevacizumabAlso: Avastin5 mg/kg every 2 weeks for up to 24 weeks. After 24 weeks, those patients without disease progression will receive bevacizumab 7.5 mg/kg every 3 weeks until progression of disease or unacceptable toxicity. | Drug | bevacizumab before chemotherapy, bevacizumab with chemotherapy |
| OxaliplatinAlso: Eloxatin85mg/m2 IV every 2 weeks for up to 24 weeks | Drug | bevacizumab before chemotherapy, bevacizumab with chemotherapy |
| levo-folinic acidAlso: Lederfolin200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks | Drug | bevacizumab before chemotherapy, bevacizumab with chemotherapy |
| 5-fluorouracilAlso: Fluorouracil400 mg/m2 IV bolus followed by 2400 mg/m2 IV infusion over 46 hours, every 2 weeks for up to 24 weeks (given in mFOLFOX-6 schedule) | Drug | bevacizumab before chemotherapy, bevacizumab with chemotherapy |
| CapecitabineAlso: Xeloda1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) | Drug | bevacizumab before chemotherapy, bevacizumab with chemotherapy |
Primary outcome
Objective Response Rate
Time frame: Objective response was assessed by computed tomographic scan or other appropriate imaging at weeks 12 and 24 from randomization, and every 3 months thereafter, assessed up to 90 months.
Objective response rate (ORR), according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, was the primary end point and was defined as the number of complete plus partial responses divided by the number of enrolled patients. Per RECIST v 1.1 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.
4 secondary outcomes
Disease Control Rate
Time frame: At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months
Overall Survival
Time frame: assessed up to 90 months
Progression-free Survival (PFS)
Time frame: assessed up to 90 months
Toxic Effects
Time frame: up to 4 weeks after the end of the treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34309665Avallone A, Piccirillo MC, Nasti G, Rosati G, Carlomagno C, Di Gennaro E, Romano C, Tatangelo F, Granata V, Cassata A, Silvestro L, De Stefano A, Aloj L, Vicario V, Nappi A, Leone A, Bilancia D, Arenare L, Petrillo A, Lastoria S, Gallo C, Botti G, Delrio P, Izzo F, Perrone F, Budillon A. Effect of Bevacizumab in Combination With Standard Oxaliplatin-Based Regimens in Patients With Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jul 1;4(7):e2118475. doi: 10.1001/jamanetworkopen.2021.18475.
- Derived from this study: PubMed 26857924Avallone A, Piccirillo MC, Aloj L, Nasti G, Delrio P, Izzo F, Di Gennaro E, Tatangelo F, Granata V, Cavalcanti E, Maiolino P, Bianco F, Aprea P, De Bellis M, Pecori B, Rosati G, Carlomagno C, Bertolini A, Gallo C, Romano C, Leone A, Caraco C, de Lutio di Castelguidone E, Daniele G, Catalano O, Botti G, Petrillo A, Romano GM, Iaffaioli VR, Lastoria S, Perrone F, Budillon A. A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme). BMC Cancer. 2016 Feb 8;16:69. doi: 10.1186/s12885-016-2102-y.
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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
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 Bevacizumab, Oxaliplatin and levo-folinic acid in people with Colorectal Cancer, run by National Cancer Institute, Naples at 1 site 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 9 inclusion and 19 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 12 Apr 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 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 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?
Yes. Results are posted in the registry (first posted 12 Apr 2023). 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?
Objective Response Rate (time frame: Objective response was assessed by computed tomographic scan or other appropriate imaging at weeks 12 and 24 from randomization, and every 3 months thereafter, assessed up to 90 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01718873, which also lists 2 linked publications.
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 12 Apr 2023; AzTrials last refreshed its copy on 8 Nov 2026.