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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-003989-26 | EudraCT Number |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| preoperative chemoradiotherapy | Experimental | Preoperative radiation therapy and combination chemotherapy plus bevacizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiation therapy | Radiation | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | In 8 weeks after completion of chemoradiotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Up to 8 weeks after surgery |
| Number of Patients With Sphincter Preservation |
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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 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Concomitant - Schedule A | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) |
| FG001 | Sequential - Schedule B | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Concomitant - Schedule A | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) |
| BG001 |
| 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 | 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. | Posted | Number | percentage of participants | In 8 weeks after completion of chemoradiotherapy |
|
5 years
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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 | Concomitant - Schedule A | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Antonio Avallone | National Cancer Institute of Naples | +39 081 5903629 | a.avallone@istitutotumori.na.it |
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| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D000077150 | Oxaliplatin |
| C068874 | raltitrexed |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
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| Oxaliplatin | Drug | 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) |
|
| Raltitrexed | Drug | 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 acid | Drug | 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-fluorouracil | Drug | 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) |
|
| Bevacizumab | Drug | 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) |
|
Sphincter preservation in patients with tumor < 5 cm from anal verge in 8 weeks after chemoradiation therapy
| 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. | 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. | 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. | 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. | In 8 weeks after chemoradiation therapy completion |
| Sequential - Schedule B |
Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Distance of mesorectal Fascia (MRF) < 5 mm | Count of Participants | Participants |
|
| OG001 | Sequential - Schedule B | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). |
|
|
| Secondary | Number of Participants With Adverse Events | Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Posted | Count of Participants | Participants | Up to 8 weeks after surgery |
|
|
|
| Secondary | Number of Patients With Sphincter Preservation | Sphincter preservation in patients with tumor < 5 cm from anal verge in 8 weeks after chemoradiation therapy | Posted | Count of Participants | Participants | In 8 weeks after chemoradiation therapy |
|
|
|
| Secondary | 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. | PFS for the schedule A was not calculated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested and, consequently, the accrual was early terminated. | Posted | Number | participants | 10 years |
|
|
|
| Secondary | Overall Survival (OS) | OS was calculated from the date of initial treatment to the date of death for any cause or last follow up. | OS for the schedule A was not calculated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested and, consequently, the accrual was early terminated. | Posted | Number | participants | 10 years |
|
|
|
| Secondary | 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. | Posted | Number | percentage of participants | 7 weeks after chemoradiation therapy up to 11 weeks |
|
|
|
| Secondary | Patients With Metastatic Lymphnodes at Pathology Exam After Surgery | Number of patients with metastatic lymphnodes at pathology exam after surgery. | Posted | Number | participants | In 8 weeks after chemoradiation therapy completion |
|
|
|
| 5 |
| 16 |
| 7 |
| 16 |
| 7 |
| 16 |
| EG001 | Sequential - Schedule B | Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). | 6 | 46 | 14 | 46 | 22 | 46 |
| Nausea/Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Proctitis | Gastrointestinal disorders | Systematic Assessment |
|
| Asthenia | General disorders | Systematic Assessment |
|
| Hypertension | Blood and lymphatic system disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
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| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| 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 |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |