E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gastroesophageal cancer |
Oesophagus- en maagcarcinoom |
|
E.1.1.1 | Medical condition in easily understood language |
Gastroesophageal cancer |
Slokdarm- en maagkanker |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effects of the combination of two chemotherapies followed by immunostimulants on the interferon gamma expression and infiltration of cytotoxic T cells in the tumour microenvironment |
Onderzoeken welk effecten de combinatie van twee chemokuren gevolgd door immuunstimulerende middelen heeft op de interferon gamma expressie en infiltratie van cytotoxische T cellen in the tumor microenvironment
|
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E.2.2 | Secondary objectives of the trial |
Secondary objectives - Overall survival and compare with a propensity score matched cohort from the Dutch randomized phase 2 LyRICX study and Dutch Cancer Registry - Progression free survival and compare with a propensity score matched cohort - Response rate according to RECIST 1.1 - Adverse events according to NCI CTCAE version 5.0 - Quality of life - Percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of treatment - Reasons for forgoing subsequent treatment after progression
Exploratory endpoints: 1 Explore the impact of cytotoxic therapy on the tumor immune microenvironment 2 Identify candidate markers of response to PD-1 pathway inhibitors and potential aetiologies of de novo or acquired resistance 3 Explore whether 1 and 2 are related to response to treatment and survival 4 Patient derived tumor organoids and autologous immune cell co-culturing to asses markers of response to treatment and identify resistance pathways |
Secundaire eindpunten: - Algehele overleving en vergelijken met een propensity score gematched cohort uit de Nederlandse gerandomiseerde fase 2 LyRICX studie en de Nederlandse Kanker registratie - Progressievrije overleving en vergelijking met een propensity score gematched cohort - Response rate volgens RECIST 1.1 - Bijwerkingen volgens NCI CTC versie 5.0 - Kwaliteit van leven - Percentage patiënten dat aan een volgende lijn behandeling start en de inhoud van die behandelingen - Redenen voor het starten van de volgende lijnen van behandeling
Exploratieve eindpunten: 1 Bepalen van het effect van cytotoxische therapie op de tumor immuun micro-omgeving 2 Identificeren van kandidaat-markers van respons op PD-1 pathway remmers 3 Bepalen of 1 en 2 gerelateerd zijn aan respons op behandeling en overleving 4 Maken van tumororganoïden van patienten en autologe immuun co-culturen om markers van respons op behandeling te bepalen en resistentiepathways te identificeren |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female adult patients (> 18 years) - Primaire tumor or metastasis accessible for repeat fresh histological biopsies - dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 - Patients with histologically confirmed diagnosis of metastatic or irresectable HER2 negative adenocarcinoma of the stomach or oesophagus; patients with HER2 positive disease are eligble when treatment with trastuzumab is contraindicated. If histology cannot be obtained, cytology is acceptable to prove metastatic disease - Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is allowed if other untreated lesions eligble for evaluation are present - Measurable disease as assessed by RECIST 1.1 - ECOG (WHO) performace status 0-2 - Patient has adequate hepatic, renal and hematological function |
- Volwassen patienten (> 18 jaar) - Primaire tumor of metastase beschikbaar voor meerdere biopten - dMMR geidentificeerd door IHC of mismatch repair proteins MLH1, PMS2, MSH2, en MSH6 - Histologisch bewezen gemetastaseerd of irresectabel HER 2 negatief adenocarcinoom van slokdarm of maag - Meetbare ziekte volgens RECIST 1.1 - ECOG (WHO) performance status 2.0 - Patienten met gemetastaseerd of irresectabel HER 2 negatief adenocarcinoom van slokdarm of de maag di enog niet behandeld zijn met chemotherapie of radiotherapie voor irresectabele of gemetastaseerde ziekte. Palliatieve radiotherapie van de primaire tumor is toegestaan als andere niet behandelde leasies evalueerbaar zijn - Patient heeft adequate lever, nier en been merg functies |
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E.4 | Principal exclusion criteria |
- Past or current malginancy other than entry diagnosis interfering with prognosis of metastatic esophagogastric cancer |
- de aanwezigheid van een andere maligniteit die interfereert met de prognose van de slokdarm-maagkanker |
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E.5 End points |
E.5.1 | Primary end point(s) |
Interferon gamma expression and number of infiltrating cytotoxic T cells |
Interferon gamma expressie en aantal infiltrerende cytotoxische T cellen |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Fresh tumor biopsies, faeces and blood in week 0, week 6, week 14. Extra blood sample in week 7. |
Tumor biopten, bloed en faecus in week 0, week 6 en week 14. Extra bloed sample in week 7. |
|
E.5.2 | Secondary end point(s) |
- overall survival - progression free survival - response rate according to RECIST 1.1 - Adverse events according to NCI CTCAE version 5.0 - Quality of life - Percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of subsequent treatments - Reasons for forgoing subsequent treatment after progression
|
- Overall survival - Response rate volgens RECIST 1.1 - Bijwerkingen volgens NCI CTC versie 5.0 - Kwaliteit van leven - Percentage van patienten die met een volgende lijn behandeld worden en het beschrijven van die behandeling - Redenen voor het doorgaan met een andere lijn na progressie |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- CT scan in week 0, week 6, week 14, and every 12th week until progression - Laboratory assessment at start of each cycle - questionnaire neurotoxicity every 3 weeks, up until week 9 - questionnaire quality of life every 12 weeks |
- CT scan in week 1, week 6, week 14, en elke 12e week tot progressie - Onderzoek van bloed aan het begin van elke cyclus - vragenlijst neurotoxiciteit elke 3 weken, tot week 9 - vragenlijst kwaliteit van leven elke 12 weken |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last visit of the last subject |
Laatste bezoek van de laatste patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 42 |
E.8.9.1 | In the Member State concerned days | |