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 CancerPhase 2ATOMNCT01836653

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

A Phase 2 study testing Bevacizumab, Cetuximab and L-OHP in people with 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, run by EPS Corporation at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 20 to 80 years
Conditions the study is 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
What is being tested?: Bevacizumab, Cetuximab and L-OHP
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 122 participants
Where: 1 siteJapan
Study dates: May 2013to Mar 2017
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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
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
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:

Show all 16Show fewer

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

Who cannot join

Previously experienced severe allergic reaction to drugs
Receiving anti-platelet drugs (aspirin >= 325 mg/day) or NSAIDs
Receiving chronic systemic corticosteroid treatment
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.
Severe postoperative complications (e.g. postoperative infection, anastomic dehiscence or paralytic ileus)
Diagnosed as hereditary colorectal cancer

Show all 19Show fewer

Active other malignancies
Cerebrovascular disease or symptoms less than 1 year prior to entry
Pleural effusion, ascites or cardiac effusion requiring drainage
Hemorrhage/bleeding, paralytic ileus, obstruction or ulceration of gastrointestinal tract
Perforation of gastrointestinal tract less than 1 year prior to entry
Presence of active infection
HBs antigen or HCV antibody positive
Uncontrolled comorbidity including hypertension, diabetes, arrhythmia, or other diseases (such as cardiac disorder, interstitial pneumonia or renal disorder)
Presence of >= grade 2 diarrhea
Presence of >= grade 1 peripheral neuropathy
Pregnant or lactating women. Women and men with childbearing potential unwilling to use effective means of contraception
Psychosis or psychiatric symptoms who are not able to comply with the protocol
Any other medical conditions disable to comply with the protocol

Trial locations and contacts

1 site in 1 country.

Japan1 site

EPS Corporation
Shinjuku-ku, Tokyo, 162-0814

Other trials in Japan

About this study

Official title: Randomized Phase II Study of mFOLFOX6 + Bevacizumab or mFOLFOX6 + Cetuximab in Liver Only Metastasis From KRAS Wild Type Colorectal Cancer

Read the 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.

Conditions: 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
Being tested: Bevacizumab, Cetuximab, L-OHP, l-LV, 5-FU
Keywords: Bevacizumab, Cetuximab, KRAS wild type colorectal cancer, RAS wild type colorectal cancer, liver metastasis
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BevacizumabDrug
Also called Avastin
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.
CetuximabDrug
Also called Erbitux
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.
L-OHPDrug
Also called Oxaliplatin
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-LVDrug
Also called Levofolinate
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.
5-FUDrug
Also called Fluorouracil
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-FUDrug
Also called Fluorouracil
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.

Study groups in NCT01836653
Study group	Role	What they receive
mFOLFOX + Bmab	Experimental	mFOLFOX plus bevacizumab Receives: Drug: Bevacizumab; Drug: L-OHP; Drug: l-LV; Drug: 5-FU
mFOLFOX + Cmab	Active comparator	mFOLFOX plus cetuximab Receives: Drug: Cetuximab; Drug: L-OHP; Drug: l-LV; Drug: 5-FU

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression-free survival
assessed by Independent Review Committee
Measured: assessed every 8 weeks, up to 4 years

Secondary outcomes (1)

Response rate
Measured: assessed every 8 weeks, up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2013Mar 2017

First posted22 Apr 2013 (estimated)
Study startMay 2013
Primary completionMar 2017
Study completionMar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials 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 CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 122 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01836653
Sponsor's protocol ID: ATOM
Other IDs: UMIN000010209
Acronym: ATOM
Status last verified: Aug 2017
First submitted: 14 Apr 2013
Last updated: 2 Aug 2017
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 31285591

Study at a glance

From the registry record, last updated by the sponsor on 2 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Phase II Study of mFOLFOX6 + Bevacizumab or mFOLFOX6 + Cetuximab in Liver Only Metastasis From KRAS Wild Type Colorectal Cancer
ClinicalTrials.gov ID: NCT01836653
Acronym / sponsor ID: ATOM / ATOM
Conditions: 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
Keywords: Bevacizumab, Cetuximab, KRAS wild type colorectal cancer, RAS wild type colorectal cancer, liver metastasis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 122 participants (actual)
Lead sponsor: EPS CorporationUniversity, hospital or other
Study start: May 2013
Primary completion: Mar 2017 (actual)
Study completion: Mar 2017 (actual)
First posted: 22 Apr 2013 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
mFOLFOX + Bmab	Experimental	Drug: Bevacizumab, Drug: L-OHP, Drug: l-LV, Drug: 5-FUmFOLFOX plus bevacizumab
mFOLFOX + Cmab	Active comparator	Drug: Cetuximab, Drug: L-OHP, Drug: l-LV, Drug: 5-FUmFOLFOX plus cetuximab

Who may qualify

Ages: 20 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (16 listed)

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.

Key exclusion criteria (19 listed)

Previously experienced severe allergic reaction to drugs
Receiving anti-platelet drugs (aspirin >= 325 mg/day) or NSAIDs
Receiving chronic systemic corticosteroid treatment
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.
Severe postoperative complications (e.g. postoperative infection, anastomic dehiscence or paralytic ileus)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BevacizumabAlso: Avastin5 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.	Drug	mFOLFOX + Bmab
CetuximabAlso: Erbitux250 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.	Drug	mFOLFOX + Cmab
L-OHPAlso: Oxaliplatin85 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.	Drug	mFOLFOX + Bmab, mFOLFOX + Cmab
l-LVAlso: Levofolinate200 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.	Drug	mFOLFOX + Bmab, mFOLFOX + Cmab
5-FUAlso: Fluorouracil400 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.	Drug	mFOLFOX + Bmab, mFOLFOX + Cmab
5-FUAlso: Fluorouracil2400 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.	Drug	mFOLFOX + Bmab, mFOLFOX + Cmab

Primary outcome

Progression-free survival
Time frame: assessed every 8 weeks, up to 4 years
assessed by Independent Review Committee

1 secondary outcome

Response rate
Time frame: assessed every 8 weeks, up to 4 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2017.
Derived from this study: PubMed 31285591Oki 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Yoshihiko Maehara, MD,PhD,FACS principal investigator

Graduate School of Medical Science, Kyushu University, Department of Surgery and Science

Naohiro Tomita, MD, PhD principal investigator

Hyogo College of Medicine, Department of Surgery

Ichinosuke Hyodo, MD, PhD principal investigator

Tsukuba University, Graduate School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: assessed every 8 weeks, up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01836653, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2017.