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Achievement of Improved Survival by Molecular Targeted Chemotherapy and Liver Resection for Not Optimally Resectable Colorectal Liver Metastases (ATOM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01836653
Recruitment Status : Completed
First Posted : April 22, 2013
Last Update Posted : August 2, 2017
Sponsor:
Information provided by (Responsible Party):
EPS Corporation

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: Bevacizumab Drug: Cetuximab Drug: L-OHP Drug: l-LV Drug: 5-FU Phase 2

Detailed Description:
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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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of mFOLFOX6 + Bevacizumab or mFOLFOX6 + Cetuximab in Liver Only Metastasis From KRAS Wild Type Colorectal Cancer
Study Start Date : May 2013
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: mFOLFOX + Bmab
mFOLFOX plus bevacizumab
Drug: Bevacizumab
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.
Other Name: Avastin

Drug: L-OHP
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.
Other Name: Oxaliplatin

Drug: l-LV
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.
Other Name: Levofolinate

Drug: 5-FU
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.
Other Name: Fluorouracil

Drug: 5-FU
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.
Other Name: Fluorouracil

Active Comparator: mFOLFOX + Cmab
mFOLFOX plus cetuximab
Drug: Cetuximab
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.
Other Name: Erbitux

Drug: L-OHP
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.
Other Name: Oxaliplatin

Drug: l-LV
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.
Other Name: Levofolinate

Drug: 5-FU
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.
Other Name: Fluorouracil

Drug: 5-FU
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.
Other Name: Fluorouracil




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: assessed every 8 weeks, up to 4 years ]
    assessed by Independent Review Committee


Secondary Outcome Measures :
  1. Response rate [ Time Frame: assessed every 8 weeks, up to 4 years ]

Other Outcome Measures:
  1. Tumor shrinkage rate at 8 week [ Time Frame: assessed at 8 week, up to 8 weeks ]
  2. Liver resection rate [ Time Frame: assessed every 8 weeks, up to 4 years ]
  3. R0 liver resection rate [ Time Frame: assessed every 8 weeks, up to 4 years ]
    pathologically confirmed R0 liver resection rate

  4. Progression-free survival [ Time Frame: assessed every 8 weeks, up to 4 years ]
    assessed by investigators

  5. Time to treatment-failure [ Time Frame: assessed every 2 weeks, up to 4 years ]
  6. Overall survival [ Time Frame: assessed every 2 weeks, up to 4 years ]
  7. Quality of life [ Time Frame: assessed every 16 weeks, up to 1 year ]
  8. Incidence of adverse events [ Time Frame: assessed every 2 weeks, up to 4 years ]
  9. Progression-free survival among the RAS wild type subpopulation [ Time Frame: assessed every 8 weeks, up to 4 years ]
    All the assessment is repeated for a maximum of 4 years.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histopathologically confirmed colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer.
  2. RAS wild type
  3. Synchronous* or metachronous liver limited meitastasis with no extrahepatic desiease

    • shychronous liver limited metastasis with primary lesion less than two thirds of the circumference
    • patients with primary lesion more than two thirds of the circumference can be enrolled after primary resection
  4. 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.

  1. Neu >= 1500/mm3
  2. Pt >= 10.0x10^4/mm3
  3. Hb >= 9.0 g/dL
  4. T-bil =< 2.0 mg/dL
  5. AST and ALT =< 200 IU/L
  6. sCr =< 1.20 mg/dL
  7. INR < 1.5
  8. Proteinuria =< 2+ 11.Written informed consent

Exclusion Criteria:

  1. Previously experienced severe allergic reaction to drugs
  2. Receiving anti-platelet drugs (aspirin >= 325 mg/day) or NSAIDs
  3. Receiving chronic systemic corticosteroid treatment
  4. Surgery/ biopsy with skin incision or traumatic injury with suture less than 14 days prior to entry. Excluding, suture for implanted venous reservoirs with catherter is allowed.
  5. Severe postoperative complications (e.g. postoperative infection, anastomic dehiscence or paralytic ileus)
  6. Diagnosed as hereditary colorectal cancer
  7. Active other malignancies
  8. Cerebrovascular disease or symptoms less than 1 year prior to entry
  9. Pleural effusion, ascites or cardiac effusion requiring drainage
  10. Hemorrhage/bleeding, paralytic ileus, obstruction or ulceration of gastrointestinal tract
  11. Perforation of gastrointestinal tract less than 1 year prior to entry
  12. Presence of active infection
  13. HBs antigen or HCV antibody positive
  14. Uncontrolled comorbidity including hypertension, diabetes, arrhythmia, or other diseases (such as cardiac disorder, interstitial pneumonia or renal disorder)
  15. Presence of >= grade 2 diarrhea
  16. Presence of >= grade 1 peripheral neuropathy
  17. Pregnant or lactating women. Women and men with childbearing potential unwilling to use effective means of contraception
  18. Psychosis or psychiatric symptoms who are not able to comply with the protocol
  19. Any other medical conditions disable to comply with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01836653


Locations
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Japan
EPS Corporation
Shinjuku-ku, Tokyo, Japan, 162-0814
Sponsors and Collaborators
EPS Corporation
Investigators
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Principal Investigator: 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: EPS Corporation
ClinicalTrials.gov Identifier: NCT01836653    
Other Study ID Numbers: ATOM
UMIN000010209 ( Other Identifier: UMIN )
First Posted: April 22, 2013    Key Record Dates
Last Update Posted: August 2, 2017
Last Verified: August 2017
Keywords provided by EPS Corporation:
Bevacizumab
Cetuximab
KRAS wild type colorectal cancer
RAS wild type colorectal cancer
liver metastasis
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Bevacizumab
Cetuximab
Fluorouracil
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors