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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03158610
• Other study ID #: BIG-MOON
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: January 29, 2018
• Est. completion date: April 28, 2021

Study information

• Verified date: April 2021
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: April 28, 2021
• Est. primary completion date: April 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Capecitabine
Oral fluorouracil

Locations

Country	Name	City	State
China	Department of Oncology, Ruijin Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

André T, Tournigand C, Mineur L, Fellague-Chebra R, Flesch M, Mabro M, Hebbar M, Postel Vinay S, Bidard FC, Louvet C, de Gramont A. Phase II study of an optimized 5-fluorouracil-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: a GERCOR study. Ann Oncol. 2007 Jan;18(1):77-81. doi: 10.1093/annonc/mdl336. Epub 2006 Oct 9. — View Citation

Kareva I, Waxman DJ, Lakka Klement G. Metronomic chemotherapy: an attractive alternative to maximum tolerated dose therapy that can activate anti-tumor immunity and minimize therapeutic resistance. Cancer Lett. 2015 Mar 28;358(2):100-106. doi: 10.1016/j.canlet.2014.12.039. Epub 2014 Dec 23. Review. — View 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. — View Citation

Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, Mineur L, Carola E, Etienne PL, Rivera F, Chirivella I, Perez-Staub N, Louvet C, André T, Tabah-Fisch I, de Gramont A. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study. J Clin Oncol. 2006 Jan 20;24(3):394-400. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival 1 (PFS1)	from enrollment to progression	10 months
Primary	Progression Free Survival 2 (PFS2)	from randomization to progression	4 months
Secondary	Overall Survival (OS)	from signing informed consent to death	20 months
Secondary	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
Secondary	Number of participants with quality of life (QoL) as assessed by CTCAE v4.0	QoL from signing informed consent to death	20 months