LONsurf and G-CSF Use: Being On A Right Dose-intensity to Optimize Treatment Efficacy (LONGBOARD)
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|ClinicalTrials.gov Identifier: NCT04166604|
Recruitment Status : Recruiting
First Posted : November 18, 2019
Last Update Posted : July 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: Trifluridine/Tipiracil||Phase 2|
Trifluridine/tipiracil has demonstrated its efficacy in patients with metastatic colorectal cancer (mCRC) resistant to standard drugs (fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and panitumumab or cetuximab in case of RAS wild-type tumors). This treatment has a marketing authorization.
Neutropenia is a classic complication of cytotoxic treatments. Febrile neutropenia are associated with a mortality rate of 9.5% and a hospitalization of 6 days in median. Recent meta-analyses have reported that the use of granulocyte-colony stimulating factor (GCSF) allows to maintain the dose-intensity of cytotoxic treatment and was associated with a better overall survival (OS).
There is currently no clear recommendation for the use of G-CSF with trifluridine/tipiracil.
Unpublished analyses that various clinical parameters may be associated with the risk of neutropenia: age ≥ 65 years, female sex, level of leukocytes at baseline, and time of initial diagnostic to randomization ≥ 36 months.These data are too preliminary to allow proposing a G-CSF primary prophylaxis in a defined subgroup of patients. However, a secondary prophylaxis based on the administration of G-CSF seems efficient, with a prescription from day 14 to day 18.
The aim of this phase II study is to assess the efficacy of the secondary prophylaxis with G-CSF in case of first episode of grade 3-4 neutropenia in the aim to maintain the optimal dose intensity.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||250 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||250 patients need to be included in a prospective cohort, to obtained 89 patients in the phase II (experience a grade 3-4 neutropenia)|
|Masking:||None (Open Label)|
|Official Title:||LONsurf and G-CSF Use: Being On A Right Dose-intensity to Optimize Treatment Efficacy|
|Actual Study Start Date :||May 20, 2020|
|Estimated Primary Completion Date :||November 15, 2021|
|Estimated Study Completion Date :||June 15, 2022|
35mg/m² BID (PER OS) (one cycle every 4 weeks)
after morning and evening meal,
Days 1 through 5: 35mg/m2 (twice daily)
Days 6 through 7: recovery
Days 8 through 12: 35mg/m2 (twice daily)
Day 13 through 28: recovery
In case of first event of grade 3-4 neutropenia : patients will not have a dose reduction and will receive a secondary prophylaxis with G-CSF (filgrastim or lenograstim) during subsequent cycle: a starting 5 mg/kg/day dose of filgrastim or lenograstim as a single daily injection, for 5 days, from day 14 to day 18
In case of secondary event of grade 3-4 neutropenia despite G-CSF secondary prophylaxis, dose adjustment of trifluridine/tipiracil will be done according to Summary of Product Characteristics (SmPC). G-CSF secondary prophylaxis will be continuing with the reduction.
- Rate of patients free of trifluridine/tipiracil dose reduction or postponement of cycles of > 7 days at 6 months or at progression or death or stop of treatment for another cause than neutropenia if observed in the 6 months. [ Time Frame: At 6 months ]
- Overall survival (OS) [ Time Frame: Up to 30 months ]Overall survival (OS) is defined as the time from study enrollment to death (from any cause) or to the last date the patients was known to be alive
- Progression free survival (PFS) [ Time Frame: up to 30 months ]PFS is defined as the time (in months) from study enrollment until objective PD or death from any cause. If the patient dies before reaching PD, the date of death is considered as the date that PD was reached. For patients that had not reached PD at the time of the analysis, and for patients for whom the PD date is unknown, PFS is censored at the date of patient's final assessment prior to data cut-off.
- Objective response rate (ORR) [ Time Frame: Up to 30 months ]Objective response rate is defined as proportion of patients with reduction in tumor burden of predefined amount. It refers to the number of patients with CR, PR according to RECIST v1.1
- Disease control rate (DCR) [ Time Frame: Up to 30 months ]The disease control rate (DCR) is defined as the proportion of patients in whom the best overall response is determined as complete response, partial response or stable disease
- Number of participants with treatment-related adverse events grade 3-4 as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 [ Time Frame: up to 30 months ]Patients will be assessed for AEs throughout the study at every visit during treatment. Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs.
- Number of participants with dose reductions [ Time Frame: up to 30 months ]
- Polymorphisms analysis of ATM and XRCC3 [ Time Frame: Blood samples at baseline and at Cycle 2 Day 1 (Day 28 of cycle 1) ]
- Measure of the level of circulating tumor DNA [ Time Frame: Blood samples at baseline and at Cycle 2 Day 1 (Day 28 of cycle 1) ]Circulating cell-free DNA will be sequenced using the AmpliSeq Colon and Lung Cancer Panel V2 on an Ion Proton following the manufacturer's recommendations (Life Technology), and date will be analyzed using the BPER method.
- Measure of the level of seric growth factors TGF β [ Time Frame: Blood samples at baseline and at Cycle 2 Day 1 (Day 28 of cycle 1) ]
- Measure of the level of seric growth factors TGF α [ Time Frame: Blood samples at baseline and at Cycle 2 Day 1 (Day 28 of cycle 1) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04166604
|Contact: Marie Line GARCIA LARNICOL||01 40 20 85 firstname.lastname@example.org|
|Principal Investigator:||Jean Baptiste BACHET, MD||Hôpital Pitié Salpêtrière|