Clinical trial NCT03158610: Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Metastatic Colorectal Cancer
Official title: Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Responders After Induction Therapy in Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Colorectal Cancer
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2017-05-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Progression Free Survival 1 (PFS1)
timeFrame: 10 months
measure: Progression Free Survival 2 (PFS2)
timeFrame: 4 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 20 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 20 months
measure: Number of participants with quality of life (QoL) as assessed by CTCAE v4.0
timeFrame: 20 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Oncology, Ruijin Hospital
Study officials:
affiliation: Ruijin Hospital
name: Jun Zhang, MD & Ph. D
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, de Jongh FE, Erdkamp FL, Erjavec Z, van der Torren AM, Tol J, Braun HJ, Nieboer P, van der Hoeven JJ, Haasjes JG, Jansen RL, Wals J, Cats A, Derleyn VA, Honkoop AH, Mol L, Punt CJ, Koopman M. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015 May 9;385(9980):1843-52. doi: 10.1016/S0140-6736(14)62004-3. Epub 2015 Apr 7.
citation: Shi M, Ma T, Xi W, Jiang J, Wu J, Zhou C, Yang C, Zhu Z, Zhang J. A study of capecitabine metronomic chemotherapy is non-inferior to conventional chemotherapy as maintenance strategy in responders after induction therapy in metastatic colorectal cancer. Trials. 2020 Mar 6;21(1):249. doi: 10.1186/s13063-020-4194-6.