Nal-iri/lv5-fu Versus Paclitaxel as Second Line Therapy in Patients With Metastatic Oesophageal Squamous Cell Carcinoma (OESIRI)
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|ClinicalTrials.gov Identifier: NCT03719924|
Recruitment Status : Recruiting
First Posted : October 25, 2018
Last Update Posted : March 14, 2019
The aim of our study is to evaluate the efficacy and safety of NALIRI plus 5FU versus paclitaxel as a second-line therapy in patients with locally advanced or metastatic ESCC who had failed to cisplatin- or oxaliplatin-based first-line chemotherapy.
The hypotheses are as follows:
H0: the percentage of patients alive at 9 months of 40% is not useful. H1: the percentage of patients alive at 9 months of 60% is expected.
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma||Drug: Onivyde Drug: Paclitaxel||Phase 2|
• To evaluate the survival of patients at 9 months
- Progression-free survival (PFS) (clinical and/or radiological)
- Overall survival (OS)
- Best response rate during treatment according to RECIST 1.1 criteria (according to the investigator and the centralised review committee)
- Toxicity (NCI CTC 4.0)
- Quality of life (QLQ-C30 and OES18 questionnaires of the EORTC)
Arm A (experimental arm): Nal IRI plus LV5-FU (D1=D28) Nal-IRI: 80 mg/m² intravenous over 90 minutes Followed by intravenous folinic acid 400 mg/m² over 30 minutes or L-folinic acid: 200 mg/m² over 30 minutes And then 5-FU 2,400 mg/m² over 46 hours on D1 to D14 Patients known to be homozygous for the UGT1A1*28 allele who are to be randomized to the Nal-IRI/5-FU Arm receive the first cycle of therapy with a reduced dose of Nal IRI of 60 mg/m2. If the patient does not present any toxicity related to the medicinal product after the first administration of Nal IRI, the dose can be increased to 80 mg/m2 starting with cycle 2.
Arm B (control arm): PACLITAXEL (D1=D28) Paclitaxel: 80 mg/m² at D1, D8 and D15
Patients will be randomized in a 1:1 ratio using the minimisation technique. Randomisation will be stratified based on the following factors:
- WHO performance status: 0/1 versus 2
An analysis of circulating tumour DNA (using genetic mutations, in particular, TP53, and DNA methylation analyses) will be performed before the 1st cycle of treatment and at D28, in order to look for factors predictive of response to treatment (decrease in unbound DNA).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||106 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
All initial characteristics will be described in the overall population and by treatment arm. Evaluation criteria related to efficacy and safety will be described by treatment arm. Initial characteristics of best response and toxicities will be evaluated using usual statistics: for quantitative variables: mean, standard deviation, median, interquartile interval and range and for qualitative variables: frequencies and percentages.
For the primary evaluation end point, a one-sided 95% confidence interval (CI) will be calculated in the experimental arm.
|Masking:||None (Open Label)|
|Official Title:||Nal-IRI/LV5-FU VERSUS PACLITAXEL AS SECOND-LINE THERAPY IN PATIENTS WITH METASTATIC OESOPHAGEAL SQUAMOUS CELL CARCINOMA A Multi-centre, Randomized, Non-comparative Phase II Study|
|Actual Study Start Date :||March 7, 2019|
|Estimated Primary Completion Date :||July 15, 2021|
|Estimated Study Completion Date :||April 15, 2022|
Experimental: arm A: ONIVYDE
ONIVYDE ONIVYDE will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14 ONIVYDE: 80 mg/m² intravenous over 90 minutes Folinic acid: 400 mg/m² intravenous over 30 minutes or L-folinic acid (racemic form L) 200 mg/m² over 30 minutes 5-FU: 2400 mg/m² over 46 hours
onivyde will be administered first, followed by folinic acid or L-folinic acid and then 5-FU at D1 and D14.
Other Name: no other intervention name to add
Active Comparator: Arm B: TAXOL
TAXOL Premedication consists of corticosteroids, H1 antihistamines and H2 antagonists during 30 minutes at time 1 hour before chemotherapy One cycle every 28 days (D1=D28) 80 mg/m2 IV over 60 minutes at D1, D8 and D15
Paclitaxel : 80 mg/m2 IV during 60 minutes at D1, D8 and D15
Other Name: no other intervention name to add
- survival at 9 months [ Time Frame: 9 months ]The principal objective is to evaluate survival at 9 months in patients presenting with metastatic oesophageal squamous cell carcinoma (OSC) treated with Nal-IRI/LV5-FU or with paclitaxel.
- Progression-free survival [ Time Frame: 5 years ]Clinical Progression-free survival and/or radiological Progression free survival will be evaluated
- Overall survival (OS) [ Time Frame: 1 year ]evaluate the overall survival
- Best response rate during treatment [ Time Frame: 6 months ]Best response rate during treatment according to RECIST 1.1 criteria (according to the investigator and with centralised review)
- Toxicity (NCI-CTC v4) [ Time Frame: 6 months ]all observed toxicities, graded according to NCI-CTC v4 and the SAE
- Quality of life (questionnaires) [ Time Frame: 6 months ]Quality of life (QLQ-C30 questionnaires of EORTC) and OES18 questionnaires of EORTC
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): NCT03719924
|Contact: DAVID TOUGERON||05.49.44.37.51 ext 42109||David.TOUGERON@chu-poitiers.fr|
|Chu de Poitiers||Not yet recruiting|
|Contact: DAVID TOUGERON, PR|