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| ID | Type | Description | Link |
|---|---|---|---|
| UMIN000010209 | Other Identifier | UMIN |
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The purpose of this study is to evaluate efficacy and safety of mFOLFOX6+bevacizumab and mFOLFOX6+cetuximab for liver only metastasis from KRAS Exon 2 wild type (under protocol 1.0-1.2 edition) and RAS wild type (under protocol 2.0 edition) colorectal cancer.
Description: The purpose of this study is to evaluate efficacy and safety of mFOLFOX6+bevacizumab and mFOLFOX6+cetuximab for liver only metastasis from KRAS Exon 2 wild type (under protocol 1.0-1.2 edition) and RAS wild type (under protocol 2.0 edition) colorectal cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mFOLFOX + Bmab | Experimental | mFOLFOX plus bevacizumab |
|
| mFOLFOX + Cmab | Active Comparator | mFOLFOX plus cetuximab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bevacizumab | Drug | 5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival | assessed by Independent Review Committee | assessed every 8 weeks, up to 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Response rate | assessed every 8 weeks, up to 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor shrinkage rate at 8 week | assessed at 8 week, up to 8 weeks | |
| Liver resection rate | assessed every 8 weeks, up to 4 years | |
| R0 liver resection rate |
Inclusion Criteria:
Histopathologically confirmed colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer.
RAS wild type
Synchronous* or metachronous liver limited meitastasis with no extrahepatic desiease
Patients who has one or more lesion(s) of diameter 1 cm or larger (RECEST v1.1) be able to assess continuously on the basis of the protocol by contrast enhanced CT or contrast enhanced MRI of the liver:
(1)Liver metastases 5 or more (2)Liver metastases with 5 cm or larger in greatest dimension (3)Unresectable considering remaining hepatic function (4)Invasion into all hepatic veins or inferior vena cava (5)Invasion into both right and left hepatic arteries or portal veins 5.No prior chemotherapy for colorectal cancer including hepatic arterial infusion. Excluding postoperative and preoperative chemoradiotherapy except for rectal cancer with synchronous liver metastases. Patients received postoperative chemotherapy containing oxaliplatin have to be enrolled after 24 weeks from the last oxaliplatin administration.
6.No previous treatment including ablation therapy, cryotherapy and chemotherapy for metastases 7.Age at enrollment is >=20 and =<80 years 8.The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 9.Life expectancy from the day of enrollment is 3 months or longer 10.Major organ functions less than 14 days prior to entry meet the following criteria.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yoshihiko Maehara, MD,PhD,FACS | Graduate School of Medical Science, Kyushu University, Department of Surgery and Science | Principal Investigator |
| Naohiro Tomita, MD, PhD | Hyogo College of Medicine, Department of Surgery | Principal Investigator |
| Ichinosuke Hyodo, MD, PhD | Tsukuba University, Graduate School of Medicine | Principal Investigator |
| Michiaki Unno, MD, PhD | Tohoku University, Division of Gastroenterological Surgery | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| EPS Corporation | Shinjuku-ku | Tokyo | 162-0814 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31285591 | Derived | Oki E, Emi Y, Yamanaka T, Uetake H, Muro K, Takahashi T, Nagasaka T, Hatano E, Ojima H, Manaka D, Kusumoto T, Katayose Y, Fujiwara T, Yoshida K, Unno M, Hyodo I, Tomita N, Sugihara K, Maehara Y. Randomised phase II trial of mFOLFOX6 plus bevacizumab versus mFOLFOX6 plus cetuximab as first-line treatment for colorectal liver metastasis (ATOM trial). Br J Cancer. 2019 Jul;121(3):222-229. doi: 10.1038/s41416-019-0518-2. Epub 2019 Jul 9. |
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|
| Cetuximab | Drug | 250 mg/m2 intravenously administered over 60 minutes (400 mg/m2 over 120 minutes as the initial dose) on day 1 and day 8 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease. |
|
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| L-OHP | Drug | 85 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease. |
|
|
| l-LV | Drug | 200 mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease. |
|
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| 5-FU | Drug | 400 mg/m2 intravenous bolus on day 1 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease. |
|
|
| 5-FU | Drug | 2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle. Liver resection if resectable after 8 cycles or continue until progression of disease. |
|
|
pathologically confirmed R0 liver resection rate |
| assessed every 8 weeks, up to 4 years |
| Progression-free survival | assessed by investigators | assessed every 8 weeks, up to 4 years |
| Time to treatment-failure | assessed every 2 weeks, up to 4 years |
| Overall survival | assessed every 2 weeks, up to 4 years |
| Quality of life | assessed every 16 weeks, up to 1 year |
| Incidence of adverse events | assessed every 2 weeks, up to 4 years |
| Progression-free survival among the RAS wild type subpopulation | All the assessment is repeated for a maximum of 4 years. | assessed every 8 weeks, up to 4 years |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D000068818 | Cetuximab |
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| 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 |
| 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 |
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