Clinical Trial Results:
RE-ExPEL
A pilot study of ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic adenocarcinoma of the stomach or the gastroesophageal junction, after treatment failure on a ramucirumab based therapy
Summary
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EudraCT number |
2020-001075-32 |
Trial protocol |
DE |
Global end of trial date |
20 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Sep 2023
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First version publication date |
20 Sep 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
RE-ExPEL
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04517747 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
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Sponsor organisation address |
Steinbacher hohl 2-26, Frankfurt am Main, Germany, 60488
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Public contact |
Dr. Claudia Pauligk, Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, info@ikf-khnw.de
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Scientific contact |
Dr. Claudia Pauligk, Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest, info@ikf-khnw.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Feb 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Jan 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine whether a combination of ramucirumab, beyond progression after a SOC 2nd line ramucirumab based pre-treatment (Ram beyond progression) in patients with locally advanced or metastatic adenocarcinoma, plus TAS-102 shows good tolerability without safety issues regarding the serious adverse event rate of any cause.
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Protection of trial subjects |
This clinical study was designed and shall be implemented and reported in accordance with the protocol, the AMG (Arzneimittelgesetz), the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC), and with the ethical principles laid down in the Declaration of Helsinki. The trial was authorized/approved by the competent authority (Paul-Ehrlich-Institut, PEI) and the competent ethics committee responsible for the trial (“federführende Ethikkommission”). Before recruitment into the clinical trial, each patient was informed that participation in the study is completely voluntary, and that he or she may withdraw his or her participation in the trial at any time without any declaration of reasons, which will not lead to any disadvantage for the respective patient. The eligibility of a new patient was determined by the local investigator during regular clinical visits. The examinations for the study and the inclusion of the patient were done after detailed written and oral education about aims, methods, anticipated benefits and potential hazards of the study by use of the informed consent forms and after given written consent of the patient. Safety was monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Oct 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
20
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited by the investigator during regular clinical visits in registered trial sites. Recruitment to the study started on October 28th, 2020 and ended on August 11th, 2021. A total of 22 patients was screened and 20 patients from a total of 3 different study sites were enrolled. | ||||||||||||
Pre-assignment
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Screening details |
Eligible patients were ≥18 years, had histologically confirmed locally advanced or metastatic gastroesophagal adenocarcinoma and showed disease progression during or within 4-6 weeks after the last dose of a ramucirumab based 2nd line therapy and had ECOG ≤2. | ||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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Experimental Arm | ||||||||||||
Arm description |
patients received ramucirumab plus TAS-102 for a maximum of 4 cycles (approx. 4months), whereat TAS-102 was prescribed and administered within its label and according to clinical routine and thus represents Standard of Care (SOC) treatment | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Ramucirumab
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Investigational medicinal product code |
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Other name |
IMC-1121B, Cyramza
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Infusion , Intravenous use
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Dosage and administration details |
8 mg/kg, i.v. on day 1 and day 15 of a 28-day cycle
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Investigational medicinal product name |
TAS-102
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Investigational medicinal product code |
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Other name |
Trifluridine/tipiracil, Lonsurf
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
35 mg/m2 p.o., twice daily on day 1 to 5 and day 8 to 12 of a 28-day cycle
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial (overall period)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental Arm
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Reporting group description |
patients received ramucirumab plus TAS-102 for a maximum of 4 cycles (approx. 4months), whereat TAS-102 was prescribed and administered within its label and according to clinical routine and thus represents Standard of Care (SOC) treatment |
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End point title |
Rate of serious adverse events [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
from the date the patient has received the first therapy dose and up to 30 days after the end of the last treatment cycle
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: In this pilot phase only 20 patients were treated with the combination therapy for tolerability and safety assessment of the combination of TAS-102 plus ramucirumab beyond progression with the aim of generating sufficient data to allow for the decision on a possible continuation in a randomized study. The evaluation was purely descriptive, and the primary endpoint therefore was not statistically evaluated. |
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No statistical analyses for this end point |
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End point title |
Patients having grade 3 or more AEs for febrile neutropenia or neutrophil count decreased | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from the date the patient has received the first therapy dose and up to 30 days after the end of the last treatment cycle
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No statistical analyses for this end point |
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End point title |
Patients having grade 3 or more AEs for anemia | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from the date the patient has received the first therapy dose and up to 30 days after the end of the last treatment cycle
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No statistical analyses for this end point |
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End point title |
Patients having grade 3 or more AEs for leukopenia | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from the date the patient has received the first therapy dose and up to 30 days after the end of the last treatment cycle
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No statistical analyses for this end point |
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End point title |
Patients having grade 3 or more AEs for thrombocytopenia | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from the date the patient has received the first therapy dose and up to 30 days after the end of the last treatment cycle
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No statistical analyses for this end point |
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End point title |
Progression-free survival | ||||||||
End point description |
If no information will be available for the evaluation of progression, patients will be censored at the timepoint of last tumor assessment
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End point type |
Secondary
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End point timeframe |
from enrollment to the first documented evidence of disease progression or death from any cause
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Attachments |
PFS |
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No statistical analyses for this end point |
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End point title |
Overall survival | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from enrollment to the date of death from any cause
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Attachments |
OS |
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No statistical analyses for this end point |
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End point title |
Best overall response | ||||||||||||
End point description |
tumor assessment was performed q8w during the study treatment and q12w in the follow-up
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End point type |
Secondary
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End point timeframe |
from start of treatment to the first documented evidence of disease progression
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
from the date the patient has received the first therapy dose and up to 30 days after the end of the last treatment cycle
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
All patients who receive at least one dose of study medication will be included in the safety analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |