Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Terminated
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
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;
Sites / Locations
- Department of Oncology, Ruijin Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Capecitabine metronomic chemotherapy
Capecitabine standard dosage chemotherapy
Arm Description
Capecitabine 500mg/m2 bid po qd
Capecitabine 1000mg/m2 bid po d1-d14,q3w
Outcomes
Primary Outcome Measures
Progression Free Survival 1 (PFS1)
from enrollment to progression
Progression Free Survival 2 (PFS2)
from randomization to progression
Secondary Outcome Measures
Overall Survival (OS)
from signing informed consent to death
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
drug related toxicity from signing informed consent to death
Number of participants with quality of life (QoL) as assessed by CTCAE v4.0
QoL from signing informed consent to death
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03158610
Brief Title
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
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
Difficult to enrollment patient
Study Start Date
January 29, 2018 (Actual)
Primary Completion Date
April 28, 2021 (Actual)
Study Completion Date
April 28, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Capecitabine metronomic chemotherapy
Arm Type
Experimental
Arm Description
Capecitabine 500mg/m2 bid po qd
Arm Title
Capecitabine standard dosage chemotherapy
Arm Type
Active Comparator
Arm Description
Capecitabine 1000mg/m2 bid po d1-d14,q3w
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
Oral fluorouracil
Primary Outcome Measure Information:
Title
Progression Free Survival 1 (PFS1)
Description
from enrollment to progression
Time Frame
10 months
Title
Progression Free Survival 2 (PFS2)
Description
from randomization to progression
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
from signing informed consent to death
Time Frame
20 months
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
drug related toxicity from signing informed consent to death
Time Frame
20 months
Title
Number of participants with quality of life (QoL) as assessed by CTCAE v4.0
Description
QoL from signing informed consent to death
Time Frame
20 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Zhang, MD & Ph. D
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology, Ruijin Hospital
City
Shanghai
ZIP/Postal Code
200025
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
25541061
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.
Results Reference
background
PubMed Identifier
16421419
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, Andre 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. doi: 10.1200/JCO.2005.03.0106.
Results Reference
background
PubMed Identifier
17030548
Citation
Andre 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.
Results Reference
background
PubMed Identifier
25862517
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.
Results Reference
background
PubMed Identifier
32143730
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.
Results Reference
derived
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Biological-guided Metronomic Chemotherapy as Maintenance Strategy in Metastatic Colorectal Cancer
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