XELOX/mFOLFOX Plus Vitamin D3 vs. XELOX/mFOLFOX as Firstline Chemotherapy in mCRC

Study Overview
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Brief Summary
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The study is a randomized,multicenter, double-blinded,phase III study. To explore the affection of vitamin D3 in combination with oxaliplatin plus fluoropyrimidine versus oxaliplatin plus fluoropyrimidine as first-line chemotherapy in previously untreated advanced or metastatic colorectal cancer.

Official Title
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A Randomized, Multicenter, Double-blinded, Phase III Study of Vitamin D3 in Combination With Oxaliplatin Plus Fluoropyrimidine Versus Oxaliplatin Plus Fluoropyrimidine as First-line Chemotherapy in Previously Untreated Advanced or Metastatic Colorectal Cancer

Conditions
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Vitamin D3

Intervention / Treatment
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* Drug: vitamin D3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent. males and females, ≥18 years of age All subjects must have inoperable, advanced or metastatic colorectal cancer and have confirmed histologically adenocarcinoma. Subject must be previously untreated with systemic treatment given as primary therapy for advanced or metastatic disease. Prior adjuvant or neoadjuvant chemotherapy and/or radiotherapy are permitted as long as the last administration of the last regimen occurred at least 12 months prior to randomization. ECOG performance status score of 0 or 1. Subjects must have at least one measurable lesion or evaluable disease by CT of MRI per RECIST1.1 criteria. Screening laboratory values must meet the following criteria in 7days before the first day of cycle 1: Hemoglobin ≥9.0g/dL; Neutrophils ≥1500/mm3; Platelet ≥100,000/mm3; Total Bilirubin ≤1.5*ULN AST ≤2.5*ULN (or ≤5.0*ULN if liver metastases are present), and ALT ≤2.5*ULN (or ≤5.0*ULN if liver metastases are present) Serum creatinine ≤1.5*ULN or calculated creatinine clearance >50mL/min Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before randomization. All subjects of childbearing potential must agree to follow instructions for method of contraception for the duration of study treatment and 6 months after the last dose of study treatment. Life expectancy ≥3 months. Exclusion Criteria: Concurrent diseases: Prior malignancy active cancer except for locally curable cancer that have been cured over 5years,or carcinoma in situ. Known brain metastasis Any serious or uncontrolled medical disorder or active infection. Known history of positive test for HIV or AIDS; Hepatitis B virus or hepatitis C virus is active; Within 4 weeks before randomization had operation, enlarged area radiotherapy(local radiotherapy within 2weeks) and other study drugs. Subjects with ≥ Grade 2 peripheral neuropathy. Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 group<br>vitamin D3 2000IU (400IU*5pills） po. qd continue to disease progression plus XELOX (oxaliplatin 130mg/m2 d1; capecitabine 1000mg/m2 bid po. d1-14; q3w) or mFOLFOX (oxaliplatin 85mg/m2，d1; leucovorin 400mg/m2，d1；5-fluorouracil 400mg/m2，d1; 5-fluorouracil 2400mg/m2 continue 46h, q2w) | Drug: vitamin D3<br>* vitamin D3 400IU*5pills po. qd continue to disease progression<br>|
| Placebo Comparator: control group<br>placebo 5 pills po. qd continue to disease progression plus XELOX (oxaliplatin 130mg/m2 d1; capecitabine 1000mg/m2 bid po. d1-14; q3w) or mFOLFOX (oxaliplatin 85mg/m2，d1; leucovorin 400mg/m2，d1；5-fluorouracil 400mg/m2，d1; 5-fluorouracil 2400mg/m2 continue 46h, q2w) | Drug: Placebo<br>* placebo 5 pills po. qd continue to disease progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS(progression-free survival) | PFS is defined the time from the date of randomization to the date of disease progression or death due to any cause. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS(overall survival) | OS is defined the time between the date of randomization and the date of death. | 5 years | 
| DCR | disease control rate | up to 1 year | 
| ORR | overall response rate | up to 1 year | 
| Incidence of Treatment-Emergent Adverse Events | all the adverse events | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRC, oxaliplatin plus fluoropyrimidine