Clinical Trial Results:
Avelumab + Paclitaxel/ Ramucirumab as second line treatment in gastro-esophageal adenocarcinoma: a phase II trial of the AIO. The RAP-Trial.
|
Summary
|
|
EudraCT number |
2018-002938-20 |
Trial protocol |
DE |
Global end of trial date |
29 Nov 2022
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
27 Jan 2024
|
First version publication date |
27 Jan 2024
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
AIO-STO-0218
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03966118 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Charité - Universitätsmedizin Berlin
|
||
Sponsor organisation address |
Charitéplatz 1, Berlin, Germany, 10117
|
||
Public contact |
PD Dr. med. Peter Thuss-Patience, Charité-University Medicine Berlin – Campus Virchow Klinikum
Med. Klinik m.S. Hämatologie, Onkologi, +49 30 450653193, peter.thuss@charite.de
|
||
Scientific contact |
PD Dr. med. Peter Thuss-Patience, Charité-University Medicine Berlin – Campus Virchow Klinikum
Med. Klinik m.S. Hämatologie, Onkologi, +49 30 450653193, peter.thuss@charite.de
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
14 Dec 2022
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
29 Nov 2022
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
29 Nov 2022
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary clinical objective is to determine the efficacy of a standard second-line regimen (paclitaxel + ramucirumab) with avelumab in patients with metastatic gastro-oesophageal cancer in terms of overall survival rate (OSR) at 6 months (according to RECIST v1.1).
|
||
Protection of trial subjects |
The responsible investigator ensured that this study is conducted in agreement with either the Declaration of Helsinki (in its current version) or the laws and regulations in its current version.
Safety assessments will include physical examinations including vital signs (blood pressure, heart rate), performance status (ECOG), clinical laboratory profile, concomitant medication and adverse events.
All observed toxicities and side effects will be graded according to NCI CTCAE v5.0 (NCI 2018) for all patients. The adverse events will also be analysed in accordance to their relation to the study treatment. Treatment related serious adverse events rate (SAE), defined as SAEs considered possibly, probably or definitely related to treatment, will be determined.
|
||
Background therapy |
Second-line chemotherapy prolongs survival in metastatic gastro-esophageal cancer compared to best supportive care. In the RAINBOW trial (Wilke et al. 2014; Shitara et al. 2016) ramucirumab + paclitaxel was compared to placebo + paclitaxel and showed an improvement of response rate and overall survival.PD-1 and PD-L1 inhibitors are a very promising treatment option in gastro-esophageal adenocarcinoma, but currently there are no treatment options incorporating PD-1 blockade in the second line setting in gastro-esophageal adenocarcinomas . Due to these reasons a combination of PD-L1 inhibition with the best established second line chemotherapy (paclitaxel+ramucirumab) is the logical next step to improve survival of metastatic gastric cancer patients and to establish PD-L1 blockade in the second line setting in combination with the currently available best second line regimen. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Mar 2019
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 60
|
||
Worldwide total number of subjects |
60
|
||
EEA total number of subjects |
60
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
30
|
||
From 65 to 84 years |
30
|
||
85 years and over |
0
|
||
|
|||||||||||||||||
|
Recruitment
|
|||||||||||||||||
Recruitment details |
The study was conducted at 13 study sites in Germany, between Date (15/05/2019) and Date (06/11/2020). Only in 10 study sites were patients recruited. | ||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||
Screening details |
According the inclusion and exclusion criteria gastric/GEJ adenocarcinoma adult patients with documented objective radiological or clinical disease progression during or within 6 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline, docetaxel or trastuzumab were 60 patients recruited. | ||||||||||||||||
|
Period 1
|
|||||||||||||||||
Period 1 title |
overall trial (overall period)
|
||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||
Blinding implementation details |
This is a single arm, multicenter phase II trial designed to assess the clinical performance of avelumab in combination with paclitaxel and ramucirumab as second-line treatment in patients with gastric or gastro-oesohageal junction adenocarcinoma.
|
||||||||||||||||
|
Arms
|
|||||||||||||||||
|
Arm title
|
Standard Regime + Avelumab | ||||||||||||||||
Arm description |
This is a single arm, multicenter phase II trial designed to assess the clinical performance of avelumab in combination with paclitaxel and ramucirumab as second-line treatment in patients with gastric or gastro-oesohageal junction adenocarcinoma. The dose of the therapy is dependent upon the patient’s baseline body weight in kilograms and the body surface. Premedication 30 to 60 minutes prior to the first 4 infusions of avelumab is mandatory. A premedication with antihistamine (for example 4 mg dimetindenmaleat), H2 blocker (for example 50mg ranitidin), 500 mg paracetamol i.v. or oral, 10 mg dexamethason before treatment infusion. Avelumab should be administered in a setting that allows for immediate access to an intensive care unit or equivalent environment After adimistration of avelumab there must be a break of at least 30 minutes before therapy with ramucirumab is given. Also for ramucirumab a premedication with an antihistamine is recommended. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
AVELUMAB
|
||||||||||||||||
Investigational medicinal product code |
SUB180078
|
||||||||||||||||
Other name |
Bavencio
|
||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||
Routes of administration |
Concentrate for solution for infusion
|
||||||||||||||||
Dosage and administration details |
Avelumab at a dose of 10 mg/kg will be given by i.v. infusion over 60 to 90 min on day 1 and 15 of a 28-day cycle.
|
||||||||||||||||
Investigational medicinal product name |
Ramucirumab
|
||||||||||||||||
Investigational medicinal product code |
SUB32795
|
||||||||||||||||
Other name |
Cyramza
|
||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||
Routes of administration |
Concentrate for solution for infusion
|
||||||||||||||||
Dosage and administration details |
Ramucirumab at dose of 8 mg/kg will be given by i.v. infusion over 60 minutes on day 1 and 15 of a 28-day cycle.
|
||||||||||||||||
Investigational medicinal product name |
Paclitaxel
|
||||||||||||||||
Investigational medicinal product code |
SUB09583MIG
|
||||||||||||||||
Other name |
|||||||||||||||||
Pharmaceutical forms |
Infusion
|
||||||||||||||||
Routes of administration |
Concentrate for solution for infusion
|
||||||||||||||||
Dosage and administration details |
Paclitaxel at a dose of 80 mg/m2 will be given by i.v. infusion over 60 minutes on day 1, 8 and 15 of a 28-day cycle.
|
||||||||||||||||
|
|||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
overall trial
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Standard Regime + Avelumab
|
||
Reporting group description |
This is a single arm, multicenter phase II trial designed to assess the clinical performance of avelumab in combination with paclitaxel and ramucirumab as second-line treatment in patients with gastric or gastro-oesohageal junction adenocarcinoma. The dose of the therapy is dependent upon the patient’s baseline body weight in kilograms and the body surface. Premedication 30 to 60 minutes prior to the first 4 infusions of avelumab is mandatory. A premedication with antihistamine (for example 4 mg dimetindenmaleat), H2 blocker (for example 50mg ranitidin), 500 mg paracetamol i.v. or oral, 10 mg dexamethason before treatment infusion. Avelumab should be administered in a setting that allows for immediate access to an intensive care unit or equivalent environment After adimistration of avelumab there must be a break of at least 30 minutes before therapy with ramucirumab is given. Also for ramucirumab a premedication with an antihistamine is recommended. | ||
|
|||||||||||||||||
End point title |
survival (OS) rate at 6 month [1] | ||||||||||||||||
End point description |
|||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
The Overall Survival Rate at 6 months (primary endpoint) will be determined by the proportion of ITT patients being alive 6 months after treatment start with first day first cycle divided by the total number of ITT patients.
|
||||||||||||||||
| 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: If p values are calculated (e.g. for comparison of subgroups), they will be presented explicitly without referring to hypotheses or a significance level. All p values will be two-sided .Patients with higher versus lower than median T cell repertoire richness showed an elevated median OS of 20.4 compared to 8.3 months (HR 0.43, 95% CI 0.23-0.81; p=0.008). Patients with lower versus higher than median cfDNA burden: median OS of 19.2 compared to 7.3 months (HR 0.30, 95% CI 0.16-0.59; p<0.001). |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
During the course of the study all AEs and SAEs should be proactively followed up for each subject.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard Regime + Avelumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 4% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
16 Apr 2019 |
late registration of additional study site |
||
23 Jul 2019 |
late registration of additional study site |
||
08 Aug 2019 |
update Study protocol version 1.2 |
||
27 Jul 2020 |
update information about Avelimab Version 9, dated 03/06/2019
update Information about Paclitaxel and Ramucirumab (01/2020) |
||
29 Jul 2020 |
update Investigator´s Brochure Version 11 |
||
13 Jun 2022 |
Extension of the study duration until 31/12/2022 |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
