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This single arm study will assess the resection rate of liver metastasis, time to disease progression, and safety of neoadjuvant treatment with Avastin in combination with oxaliplatin and capecitabine (XELOX) in patients with metastatic colorectal cancer with unresectable liver metastasis. Patients will receive Avastin 5mg/kg iv on day 1 of every 2 week cycle, oxaliplatin 85mg/m2 iv on day 1 of every 2 week cycle, and capecitabine 1000mg/m2 on days 1-5 and 8-12 of every 2 week cycle. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bevacizumab [Avastin] | Drug | 5mg/kg iv on day 1 of each 2 week cycle. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Conversion From Unresectable to Resectable Liver Metastases | Participants were assessed via microscopic and macroscopic examination for tumor resectability after completion of 5 cycles of neoadjuvant treatment. Unresectable participants exhibited any of the following criteria: greater than or equal to (≥) 4 liver metastases; location and/or distribution of metastatic disease within the liver considered unsuitable for resection with clear margins; liver involvement precluding resection, in the setting of adequate parenchymal volume for otherwise viable liver function in the immediate postoperative period; and inability to maintain adequate circulation for viable liver function. Participants who had not met any of the above criteria at the end of 5 cycles underwent surgical resection. The percentage of participants with conversion from initially unresectable to resectable liver metastases was calculated as [number of participants eligible for surgical resection divided by the number analyzed] multiplied by 100. | After 5 cycles of neoadjuvant treatment (10 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Disease Progression | Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20 percent (%) increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kaohsiung City | 00833 | Taiwan | ||||
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| ID | Title | Description |
|---|---|---|
| FG000 | Resected | Participants with unresectable liver metastases secondary to colorectal cancer (CRC) were assigned to receive neoadjuvant treatment of intravenous (IV) bevacizumab with oral (PO) capecitabine and IV oxaliplatin (XELOX). Bevacizumab was given as 5 milligrams per kilogram (mg/kg) on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 milligrams per meter-squared (mg/m^2) on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity. |
| FG001 | Unresected | Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, repeated neoadjuvant treatment until documented resectability or progressive disease (PD). Participants could be withdrawn at any point for unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intent-to-Treat (ITT) Population: All enrolled participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Resected | Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Participants With Conversion From Unresectable to Resectable Liver Metastases | Participants were assessed via microscopic and macroscopic examination for tumor resectability after completion of 5 cycles of neoadjuvant treatment. Unresectable participants exhibited any of the following criteria: greater than or equal to (≥) 4 liver metastases; location and/or distribution of metastatic disease within the liver considered unsuitable for resection with clear margins; liver involvement precluding resection, in the setting of adequate parenchymal volume for otherwise viable liver function in the immediate postoperative period; and inability to maintain adequate circulation for viable liver function. Participants who had not met any of the above criteria at the end of 5 cycles underwent surgical resection. The percentage of participants with conversion from initially unresectable to resectable liver metastases was calculated as [number of participants eligible for surgical resection divided by the number analyzed] multiplied by 100. | ITT Population. | Posted | Number | percentage of participants | After 5 cycles of neoadjuvant treatment (10 weeks) |
Up to approximately 3 years (continuously until 4 weeks after EOT)
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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 | All Participants | Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D000069287 | Capecitabine |
| D000077150 | Oxaliplatin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| capecitabine [Xeloda] |
| Drug |
1000mg/m2 iv on days 1-5 and 8-12 of each 2 week cycle |
|
| oxaliplatin | Drug | 85mg/m2 iv on day 1 of each 2 week cycle |
|
| Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of end of treatment [EOT]) |
| Time to Disease Progression | Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Time to disease progression was defined as the time from first dose to time of disease progression. Participants without progression were censored at the time of last tumor assessment. Time to disease progression was estimated using Kaplan-Meier analysis and expressed in months. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of EOT) |
| Percentage of Participants With a Best Overall Tumor Response of Complete Response (CR) or PR According to RECIST Version 1.1 | Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was confirmed at a minimum of 4 weeks after the first documented response. The percentage of participants with confirmed CR or PR was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) |
| Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1 | Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was to be confirmed at a minimum of 4 weeks after the first documented response. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, as well as no new target lesions. Disease progression or PD was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Non-evaluability for tumor assessment was also documented when applicable. The percentage of participants with each level of response was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) |
| Kaohsiung City |
| 807 |
| Taiwan |
| Taichung | 407 | Taiwan |
| Taipei | 00112 | Taiwan |
| Taipei | 112 | Taiwan |
| Taoyuan County | 333 | Taiwan |
| Disease Progression |
|
| Withdrawal by Subject |
|
| BG001 | Unresected | Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | All Participants | Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity. |
|
|
| Secondary | Percentage of Participants With Disease Progression | Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20 percent (%) increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100. | ITT Population. | Posted | Number | percentage of participants | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of end of treatment [EOT]) |
|
|
|
| Secondary | Time to Disease Progression | Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Time to disease progression was defined as the time from first dose to time of disease progression. Participants without progression were censored at the time of last tumor assessment. Time to disease progression was estimated using Kaplan-Meier analysis and expressed in months. | ITT Population. | Posted | Median | 95% Confidence Interval | months | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of EOT) |
|
|
|
|
| Secondary | Percentage of Participants With a Best Overall Tumor Response of Complete Response (CR) or PR According to RECIST Version 1.1 | Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was confirmed at a minimum of 4 weeks after the first documented response. The percentage of participants with confirmed CR or PR was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. | ITT Population. | Posted | Number | percentage of participants | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) |
|
|
|
| Secondary | Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1 | Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was to be confirmed at a minimum of 4 weeks after the first documented response. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, as well as no new target lesions. Disease progression or PD was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Non-evaluability for tumor assessment was also documented when applicable. The percentage of participants with each level of response was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. | ITT Population. | Posted | Number | percentage of participants | Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) |
|
|
|
|
| 11 |
| 45 |
| 45 |
| 45 |
| Enteritis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Perihepatic abscess | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Intestinal anastomosis complication | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Tumour necrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Pigmentation disorder | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| SD |
|
| PD |
|
| Non-evaluable |
|