Clinical trial NCT02515734: A Study of FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: FOLFOXIRI
Bmab
Cmab
Lead sponsor: Japan Clinical Cancer Research Organization
Sponsor class: OTHER
First posted: 2015-08-05
Enrollment: 360
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Best deepness of response
timeFrame: up to 2 years
Secondary outcomes:
measure: Early tumor shrinkage
timeFrame: at 8 weeks
measure: Response rate
timeFrame: up to 2 years
measure: Deepness of response
timeFrame: at 4 months
measure: Overall survival
timeFrame: up to 2 years
measure: Progression free survival
timeFrame: up to 2 years
measure: Rate of curatively resected metastatic lesion
timeFrame: up to 2 years
measure: Number of adverse events
timeFrame: up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Japan Clinical Cancer Research Organization
name: Toshifusa Nakajima, MD
role: STUDY_DIRECTOR
References: