Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Based upon biological behavior, those mCRC patients who respond well (SD, PR or CR according to RECIST Criteria) after 16-18 weeks of standard doublet chemotherapy as induction may enrolled into this study, randomly divided into capecitabine metronomic group or standard dosage group. The duration of disease control after randomization(PFS2) and progression free survival from enrollment (PFS1) are primary endpoints. Meanwhile, the overall survival, safety and quality of life are secondary endpoints. Exploratory markers involving angiogenesis (serum VEGF, PDGF, Tie-1 and Tie2, etc) and immune function (CD clusters, serum tumor mutation burden(TMB), etc), are conducted via liquid biopsy.

Detailed Description
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This study is try to evaluate the effect of capecitabine metronomic chemotherapy as maintenance treatment, which compare to capecitabine conventional chemotherapy, who have responded to 16-18 months first-line chemotherapy in metastatic colorectal cancer (mCRC). The maintenance treatments are continued until disease progression or severe toxicity. The aim of this study is to demonstrate that capecitabine metronomic chemotherapy is non-inferior to capecitabine conventional chemotherapy. Furthermore, exploratory markers involving angiogenesis (serum VEGF, PDGF, Tie-1 and Tie2, etc) and immune function (CD clusters, serum tumor mutation burden(TMB), etc), are conducted via liquid biopsy.

Official Title
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Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Responders After Induction Therapy in Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Before the start of induction therapy: Inclusion Criteria: Histological proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained); Distant metastases which are unresectable (patients with only local recurrence are not eligible); Measurable disease (> 1 cm on spiral CT scan or > 2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation; Exclusion criteria Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months before the start of induction treatment Any prior adjuvant treatment after resection of distant metastases Previous systemic treatment for advanced disease At randomisation: Inclusion criteria: WHO performance status 0-1 (Karnofsky PS > 70%); Disease evaluation with proven SD, PR or CR according to RECIST after first-line induction treatment; Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (Hb > 6.0 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, > 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases); Life expectancy > 12 weeks; Age: 18-75 years; Negative pregnancy test in women with childbearing potential; Expected adequacy of follow-up; Institutional Review Board approval; Written informed consent Exclusion criteria Chronic active infection; Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine metronomic chemotherapy<br>Capecitabine 500mg/m2 bid po qd | Drug: Capecitabine<br>* Oral fluorouracil<br>* Other names: Xeloda;|
| Active Comparator: Capecitabine standard dosage chemotherapy<br>Capecitabine 1000mg/m2 bid po d1-d14,q3w | Drug: Capecitabine<br>* Oral fluorouracil<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival 1 (PFS1) | from enrollment to progression | 10 months | 
| Progression Free Survival 2 (PFS2) | from randomization to progression | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | from signing informed consent to death | 20 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | drug related toxicity from signing informed consent to death | 20 months | 
| Number of participants with quality of life (QoL) as assessed by CTCAE v4.0 | QoL from signing informed consent to death | 20 months |