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A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab (DEEPER)

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ClinicalTrials.gov Identifier: NCT02515734
Recruitment Status : Not yet recruiting
First Posted : August 5, 2015
Last Update Posted : August 5, 2015
Sponsor:
Information provided by (Responsible Party):
Japan Clinical Cancer Research Organization

Brief Summary:
This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: fluorouracil Drug: Leucovorin Drug: irinotecan Drug: oxaliplatin Biological: bevacizumab Biological: cetuximab Phase 2

Detailed Description:
This study is to verify the advantage of FOLFOXIRI plus cetuximab over FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer patients with RAS wild-type tumors. In this study the investigators employed deepness of response as a primary endpoint.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study to Investigate the Deepness of Response of FOLFOXIRI Plus Cetuximab (Erbitux) Versus FOLFOXIRI Plus Bevacizumab as the First-line Therapy in Metastatic Colorectal Cancer Patients With RAS Wild-type Tumors: DEEPER
Study Start Date : August 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: FOLFOXIRI+Bmab
Patients in the FOLFOXIRI + Bmab group receive until 12 cycles of FOLFOXIRI plus bevacizumab, consisting of a 30-minute infusion of bevacizumab at a dose of 5 mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and bevacizumab every 14 days until disease progression.
Drug: fluorouracil
Other Names:
  • 5-fluorouracil
  • 5-FU

Drug: Leucovorin
Other Name: Levofolinate

Drug: irinotecan
Other Name: CPT-11

Drug: oxaliplatin
Other Name: eloxatin

Biological: bevacizumab
Experimental: FOLFOXIRI+Cmab
Patients in the experimental group received until 12 cycles of FOLFOXIRI plus cetuximab, consisting of a 30-minute infusion of cetuximab first time at a dose of 400 mg per kilogram, after the second time at a dose of 250mg per kilogram, a 60-minute infusion of irinotecan at a dose of 150 mg per square meter, and a 120-minute infusion of oxaliplatin at a dose of 85 mg per square meter and a concomitant 120-minute infusion of leucovorin at a dose of 200 mg per square meter, followed by a 48-hour continuous infusion of fluorouracil to a total dose of 2400 mg per square meter. Cycles were repeated every 14 days. After 13 cycles, patients receive fluorouracil, leucovorin and cetuximab every 14 days until disease progression.
Drug: fluorouracil
Other Names:
  • 5-fluorouracil
  • 5-FU

Drug: Leucovorin
Other Name: Levofolinate

Drug: irinotecan
Other Name: CPT-11

Drug: oxaliplatin
Other Name: eloxatin

Biological: cetuximab



Primary Outcome Measures :
  1. Best deepness of response [ Time Frame: up to 2 years ]
    The maximum tumor shrinkage rates by Response Evaluation Criteria in Solid Tumors (RECIST) throughout the treatments


Secondary Outcome Measures :
  1. Early tumor shrinkage [ Time Frame: at 8 weeks ]
    The rates of tumor shrinkage by RECIST at 8 weeks

  2. Response rate [ Time Frame: up to 2 years ]
  3. Deepness of response [ Time Frame: at 4 months ]
    The tumor shrinkage rates by RECIST at 4 months

  4. Overall survival [ Time Frame: up to 2 years ]
  5. Progression free survival [ Time Frame: up to 2 years ]
  6. Rate of curatively resected metastatic lesion [ Time Frame: up to 2 years ]
  7. Number of adverse events [ Time Frame: up to 2 years ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically confirmed colorectal cancer
  • RAS wild-type
  • Measurable lesion by RECIST (Ver.1.1)
  • No past history of chemotherapy in the case of unresectable primary lesion/distant metastasis/lymph node metastasis.In the case of recurrence, no treatment for the first recurrence lesion after operation
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.The case >=71 years is PS0.
  • Life expectancy of more than 6 months
  • Patients have enough organ function for study treatment within 14 days before enrollment;

    1. White blood cell (WBC)>=3,000/mm3, <12,000/mm3.
    2. Neu>=1,500/mm3.
    3. Platelet count (PLT) >=10.0x104/mm3.
    4. Hb>=9.0g/dL.
    5. Total Bilirubin<=1.5x Upper Limited Normal (ULN)
    6. aspartate aminotransferase (AST) <=2.5xULN.
    7. alanine aminotransferase (ALT) <=2.5xULN.
    8. Creatinine<=1.5xULN.
    9. Proteinuria<=1+.
    10. prothrombin time-international normalized ratio (PT-INR) <=1.5
  • Must be able to swallow tablets
  • Written informed consent

Exclusion Criteria:

  • Synchronous multiple malignancy or metachronous multiple malignancy within 5 years disease free interval
  • Lynch syndrome
  • Brain metastases
  • Infectious disease
  • Interstitial lung disease or pulmonary fibrosis
  • Comorbidity or history of serious heart failure
  • History of thromboembolic events
  • Cerebrovascular disease
  • History of hemoptysis/hematemesis
  • Uncontrolled hypertension (systolic BP>180mmHg, or diastolic BP>100mmHg)
  • Sensory alteration or paresthesia interfering with function
  • Large quantity of pleural, abdominal or cardiac effusion
  • Severe comorbidity (renal failure, liver failure, hypertension, etc)
  • Prior radiotherapy for primary and metastases leision
  • Men/women who are unwilling to avoid pregnancy
  • Women who are pregnant or breastfeeding
  • Women with a positive pregnancy test
  • History of severe allergy
  • HBsAg positive or active viral hepatitis
  • Administration of blood products/ Granulocyte-Colony Stimulating Factor (G-CSF), and blood transfusion within 14 days
  • Surgical procedure or such as skin-open biopsy, trauma surgery, or other more intensive surgery within 28 days
  • Systematic administration of antiplatelet drug or non steroid anti-inflammatory drugs (NSAIDs)
  • Diathesis of bleeding (history of hemoptysis, including cavitation and/or necrosis in lung metastasis confirmed by imaging), coagulopathy
  • History of gastrointestinal perforation within 1 year
  • Unhealed traumatic bone fracture
  • Uncontrolled diarrhea
  • History of organ recipient
  • Prior cetuximab/bevacizumab/Irinotecan/Oxaliplatin treatment (Adjuvant therapy by Oxaliplatin is excluded)
  • Administration of atazanavir sulfate
  • Jaundice
  • Ileus or bowel obstruction
  • Clinical diagnosis of Alzheimer's Disease
  • Insulin dependent diabetes
  • Thyroid disease
  • Any other cases who are regarded as inadequate for study enrollment by investigators

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): NCT02515734


Contacts
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Contact: Masashi Fujii, MD +81-3-5579-9882 masashi.fujii@gioncology.jp
Contact: Sachika Koyama, Ms +81-3-5579-9882 cc13.dc@jaccro.or.jp

Sponsors and Collaborators
Japan Clinical Cancer Research Organization
Investigators
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Study Director: Toshifusa Nakajima, MD Japan Clinical Cancer Research Organization

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Responsible Party: Japan Clinical Cancer Research Organization
ClinicalTrials.gov Identifier: NCT02515734     History of Changes
Other Study ID Numbers: JACCRO CC-13
First Posted: August 5, 2015    Key Record Dates
Last Update Posted: August 5, 2015
Last Verified: August 2015
Keywords provided by Japan Clinical Cancer Research Organization:
FOLFOXIRI
Bmab
Cmab
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Cetuximab
Oxaliplatin
Irinotecan
Fluorouracil
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents