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A Multicenter, Clinical Study of FOLFOXIRI With Bevacizumab As First-line Therapy in Patients With mCRC (QUATTRO)

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: NCT02246049
Recruitment Status : Completed
First Posted : September 22, 2014
Last Update Posted : June 19, 2017
Sponsor:
Information provided by (Responsible Party):
EPS Corporation

Brief Summary:
The purpose of this study to assess efficacy and tolerability of combination therapy FOLFOXIRI with Bevacizumab (BV) as a first-line therapy in patients with metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Biological: Bevacizumab Drug: 5-fluorouracil Drug: Irinotecan hydrochloride Drug: Leucovorin calcium Drug: Oxaliplatin Phase 2

Detailed Description:

This is a single-arm, multicentre phase II study evaluating the efficacy and safety of Bevacizumab (BV) in combination with oxaliplatin, irinotecan hydrochloride, fluorouracil, and leucovorin calcium regimen ( FOLFOXIRI +BV ; Falcone et al. ASCO2013) as first-line treatment for Japanese metastatic colorectal cancer patients.

This study is composed two steps because of collecting safety issue in Japanese patient.

As First step (Step 1), It assess on the initial safety information in ten Japanese patients of the end of 2nd cycle. it is evaluated by DMC.

In parallel with the confirmation of the initial safety issue, register up to 65 cases in total and Step 1 patient, to evaluate the efficacy and safety (Step2).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Clinical Phase II Study of FOLFOXIRI With Bevacizumab As First-line Therapy in Patients With Metastatic Colorectal Cancer
Actual Study Start Date : May 2014
Actual Primary Completion Date : February 2017
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: FOLFOXIRI plus bevacizumab

Induction therapy is followed by the maintenance therapy.

[Induction treatment:FOLFOXIRI plus bevacizumab] Administered for a maximum of 12 cycles. BV: 5mg/kg (d.i.v.) L-OHP: 85 mg/sq.m (d.i.v.) CPT-11:165mg/sq.m (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

[Maintenance treatment:5-FU / I-LV plus bevacizumab] BV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks.

Biological: Bevacizumab
Given IV
Other Name: BV

Drug: 5-fluorouracil
Given IV
Other Name: 5-FU

Drug: Irinotecan hydrochloride
Given IV
Other Name: CPT-11

Drug: Leucovorin calcium
Given IV
Other Name: I-LV

Drug: Oxaliplatin
Given IV
Other Name: L-OHP




Primary Outcome Measures :
  1. Progression-free survival (PFS) at 10 months [ Time Frame: PFS rate at 10 months from study entry ]

    PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of treatment start to the first observation of progression disease (PD) or death from any cause.

    PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.



Secondary Outcome Measures :
  1. Response rate (RR) by central review. [ Time Frame: Up to 18 months ]
    Response evaluation was performed according to RECIST criteria v1.1.

  2. Response rate (RR) by investigator-reported measurements. [ Time Frame: Up to 30 months ]
    Response evaluation was performed according to RECIST criteria v1.1.

  3. PFS by central review according to CT image. [ Time Frame: Up to 18 months ]
    PFS was calculated from the day of treatment start to the first observation of progression disease (PD) or death from any cause.

  4. Overall survival (OS) [ Time Frame: Up to 30 months ]
    OS was calculated from the day of registration in this study to death from any cause.

  5. Efficacy by RAS status ; RR,PFS,OS [ Time Frame: Up to 30 months ]
    RR,PFS,OS according to tumor RAS status.

  6. Incidence of adverse events [ Time Frame: Up to 30 months ]
    Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All adverse events was collected in duration from starting treatment to whichever shorter "after 30 days from withdrawal treatment" or "later treatment was started".

  7. Time to treatment-failure [ Time Frame: Up to 30 months ]
  8. Completion rate in Induction treatment [ Time Frame: Up to 30 months ]
  9. Relative Dose Intensity [ Time Frame: Up to 30 months ]
  10. Treatment duration [ Time Frame: Up to 30 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Written Informed consent.
  2. Histopathologically proven diagnosis of colorectal cancer (adenocarcinoma) excluding vermiform appendix cancer and proctos cancer.
  3. Not resectable metastatic colorectal cancer
  4. Age at enrollment is >= 20 and <= 75 years
  5. ECOG PS < 2 if age < 70 years, ECOG PS = 0 if age = 71-75 years
  6. One or more measurable lesion in RECIST ver.1.1 criteria according to contrast enhanced CT chest / abdomen / pelvis diagnosis.
  7. Not previously treated with chemotherapy. ( Previous adjuvant by fluoropyrimidine monotherapy is allowed if more than 24 weeks have elapsed between the end of adjuvant therapy and first relapse.)
  8. Vital organ functions (listed below) are preserved within 2 weeks prior to entry. Data recorded nearest to the entry should be referred. Blood transfusion or erythropoiesis stimulating agents less than 2 weeks prior to the tests are not allowed.

    Neu. >= 1,500/cubicmillimeter Pt. >= 100,000/cubicmillimeter Hb. >= 9.0 g/dL T-bil. <= upper limit of normal (ULN)*1.5 AST and ALT,ALP <= upper limit of normal (ULN)*2.5 (<= ULN*5 in case of liver metastasis) Serum creatinine <= upper limit of normal (ULN) *1.5 PT-INR < 1.5 Proteinuria <= 2+

  9. UGT1A1 genotype tested. Categorized into Wild or single Hetero.

Exclusion Criteria:

  1. Previously treated with irradiation to bone marrow constituting 20% or more of irradiation field.
  2. Untreated brain metastases or spinal cord compression or primary brain tumors.
  3. History of CNS disease.[except for asymptomatic Lacunar stroke]
  4. Requiring chronic systemic corticosteroid treatment.
  5. Current or recent ongoing treatment with anticoagulants.
  6. Clinically significant cardiovascular disease for example cerebrovascular accidents, myocardial infarction, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication.
  7. Treatment with any investigational drug within 4 weeks.
  8. Patient with Uncontrolled hypertension, Uncontrolled diabetes, Uncontrolled diarrhea, >=grade 1 peripheral neuropathy, Active peptic ulcer, Non-healing wound, Clinically important diseases.
  9. Major surgical procedure within 28 days prior to study treatment start, open biopsy, or significant traumatic injury, or anticipation of the need for major surgical procedure.[except for implantation of central venous catheter and port system.]
  10. Lack of physical integrity of the upper gastrointestinal tract.
  11. Pregnant women, lactating woman , positive by pregnancy test , wishing to become pregnant, and Sexually active males.
  12. Hepatitis B or hepatitis C. Evidence of HIV infection.
  13. Previous Chemotherapy for other organs.
  14. Other active co-existing malignancies.
  15. History / Presence of thrombosis within 1 year requiring medication.
  16. History / Presence of paralytic ileus, obstruction or gastrointestinal perforation.
  17. Malignant coelomic fluid required drainage.
  18. History of allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications.
  19. History of fluoropyrimidine severe side effects caused by DPD defect.
  20. Interstitial pneumonitis or pulmonary fibrosis.
  21. Evidence or requiring systemic treatment for Infectious disease.
  22. Patient who is judged by the investigator to be inappropriate for study participation for any reason.

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): NCT02246049


Locations
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Japan
EPS Corporation
Shinjuku, Tokyo, Japan, 162-0814
Sponsors and Collaborators
EPS Corporation
Investigators
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Principal Investigator: Takeshi Kato, M.D., Ph.D Department of Surgery, National Hospital Organization Osaka National Hospital.
Principal Investigator: Akiyoshi Kanazawa, M.D., Ph.D Department of Surgery, Shimane Prefectural Central Hospital.

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Responsible Party: EPS Corporation
ClinicalTrials.gov Identifier: NCT02246049    
Other Study ID Numbers: QUATTRO
First Posted: September 22, 2014    Key Record Dates
Last Update Posted: June 19, 2017
Last Verified: June 2017
Keywords provided by EPS Corporation:
Metastatic colorectal cancer, bevacizumab, FOLFOXIRI
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
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
Immunologic Factors