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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-004997-27 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| bevacizumab before chemotherapy | Experimental | Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) |
|
| bevacizumab with chemotherapy | Active Comparator | Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bevacizumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate | Disease control rate was calculated by adding complete and partial responses and stable disease. | At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months |
| Overall Survival |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Antonio Avallone, M.D. | National Cancer Institute, Naples | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Istituto Nazionale Tumori Fondazione G. Pascale | Naples | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34309665 | Derived | 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. | |
| 26857924 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bevacizumab Before Chemotherapy | Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
| FG001 | Bevacizumab With Chemotherapy | Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bevacizumab Before Chemotherapy | Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | 95% Confidence Interval | participants | 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. |
|
Evaluated every 2 weeks up to 6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bevacizumab Before Chemotherapy | Bevacizumab administered 4 days before each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
Considering that the accuracy of conventional evaluation of tumor response by RECIST criteria to bevacizumab combination treatment has been questioned, we acknowledge that our choice of ORR as primary end point may have been inadequate.
We are also aware that balancing out unmeasurable differences in patient outcome through randomization is not always achieved with confidence in trials with a relatively small sample size.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Antonio Avallone, Dierctor of Experimental Abdominal Medcial Oncology | National Cancer Institute, IRCCS, G. Pascale Foundation | +390815903629 | a.avallone@istitutotumori.na.it |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 6, 2011 | Oct 15, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| Oxaliplatin | Drug | 85mg/m2 IV every 2 weeks for up to 24 weeks |
|
|
| levo-folinic acid | Drug | 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks |
|
|
| 5-fluorouracil | Drug | 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) |
|
|
| Capecitabine | Drug | 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
|
|
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.
| 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. | 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. | up to 4 weeks after the end of the treatment |
| Derived |
| Avallone 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. |
| BG001 | Bevacizumab With Chemotherapy | Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Bevacizumab With Chemotherapy | Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) |
|
|
| Secondary | Disease Control Rate | Disease control rate was calculated by adding complete and partial responses and stable disease. | Posted | Count of Participants | Participants | At weeks 12 and 24 from randomization and every 3 months thereafter, assessed up to 90 months |
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | months | assessed up to 90 months |
|
|
|
| Secondary | 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. | Posted | Median | 95% Confidence Interval | months | assessed up to 90 months |
|
|
|
| Secondary | 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. | any grade of toxic effects | Posted | Count of Participants | Participants | up to 4 weeks after the end of the treatment |
|
|
|
| 2 |
| 115 |
| 65 |
| 115 |
| 108 |
| 115 |
| EG001 | Bevacizumab With Chemotherapy | Bevacizumab administered on the first day of each cycle of chemotherapy containing oxaliplatin (mFOLFOX-6 / mOXXEL) Bevacizumab: 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. Oxaliplatin: 85mg/m2 IV every 2 weeks for up to 24 weeks levo-folinic acid: 200 mg/m2 IV before 5-fluorouracil infusion, every 2 weeks up to 24 weeks 5-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) Capecitabine: 1000mg/m2 by mouth, twice a day for 10 days, every 2 weeks for up to 24 weeks(given in mOXXEL schedule) | 2 | 115 | 75 | 115 | 113 | 115 |
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis oral | Infections and infestations | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Allergic reaction | Immune system disorders | Systematic Assessment |
|
| Alanine aminotransferase level increased | Hepatobiliary disorders | Systematic Assessment |
|
| Alkaline phosphatase level increased | Hepatobiliary disorders | Systematic Assessment |
|
| Neutrophil count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Platelet count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| White blood cell count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Peripheral neuropathy | Nervous system disorders | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hypertension | Cardiac disorders | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Mucositis oral | Infections and infestations | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Allergic reaction | Immune system disorders | Systematic Assessment |
|
| Alanine aminotransferase level increased | Hepatobiliary disorders | Systematic Assessment |
|
| Alkaline phosphatase level increased | Hepatobiliary disorders | Systematic Assessment |
|
| Neutrophil count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Platelet count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| White blood cell count decreased | Blood and lymphatic system disorders | Systematic Assessment |
|
| Peripheral neuropathy | Nervous system disorders | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | Systematic Assessment |
|
| Epistaxis | Vascular disorders | Systematic Assessment |
|
| Voice alteration | General disorders | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hypertension | Cardiac disorders | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
Not provided
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| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |