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

NCT01836653 | Completed Phase 2 DMC

• 2 other identifiers: ATOMUMIN000010209
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  assessed by Independent Review Committee

  assessed every 8 weeks, up to 4 years

Secondary Outcomes (1)

• Response rate

  assessed every 8 weeks, up to 4 years

Other Outcomes (9)

• 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

  assessed every 8 weeks, up to 4 years

Study Arms (2)

mFOLFOX + Bmab

EXPERIMENTAL

mFOLFOX plus bevacizumab

Drug: Bevacizumab; Drug: L-OHP; Drug: l-LV; Drug: 5-FU

mFOLFOX + Cmab

ACTIVE COMPARATOR

mFOLFOX plus cetuximab

Drug: Cetuximab; Drug: L-OHP; Drug: l-LV; Drug: 5-FU

Interventions

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.

Also known as: Avastin

mFOLFOX + Bmab

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.

Also known as: Erbitux

mFOLFOX + Cmab

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.

Also known as: Oxaliplatin

mFOLFOX + Bmab; mFOLFOX + Cmab

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.

Also known as: Levofolinate

mFOLFOX + Bmab; mFOLFOX + Cmab

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.

Also known as: Fluorouracil

mFOLFOX + Bmab; mFOLFOX + Cmab

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• (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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• EPS Corporation: lead

Study Sites (1)

EPS Corporation

Shinjuku-ku, Tokyo, 162-0814, Japan

Location

Related Publications (1)

• 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.

  PMID: 31285591 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Cetuximab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2013
• First Posted: April 22, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: August 2, 2017

Record last verified: 2017-08

Locations

JP (1)