Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Quality of Life

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Interviews and questionnaires will be performed before administration of CAR-T cells, 3 month after and 6 month after, and will last 60 minutes each time. Semi-structured interview using pre-established questionnaires will be completed with a hospital pharmacist, concerning the patient's perception of his family, socio-professional environment, his knowledge of his illness and his treatment, the consumption of prescribed drugs outside the hospital, self-medication, complementary alternative therapies including herbal medicine. Seven self-administered questionnaires will be completed, concerning quality of life, Assessment of Cancer Treatment-Lymphoma, Beliefs about Medicines, Brief Illness Perception, satisfaction with medication, perceived social support scale, and on Health Literacy.

Semi-structured interviews and self-administered questionnaires

Catherine RIOUFOL, Pharm. D

Vérane SCHWIERTZ, Pharm. D

CAR-T cells are a major therapeutic innovation in the management of patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) in 3rd line or more. Kymriah® and Yescarta® are the first CAR-T with Marketing Authorization and coverage by the French Health Insurance. Their clinical interest has been demonstrated in non-comparative phase 1-2 trials.

The non-comparative design of the pivotal trials, the lack of data on patients' quality of life and drug consumption, as well as the very high cost of CAR-T (about € 320,000 for one treatment) warrant further studies.

This prospective non-comparative study aims to describe in real life the quality of life of patients treated with CAR-T cells, real world drug use and patients' experience feedback.

Quality Of Life and Drug Use in Patients With CAR-T Cells

Pilot Study for Quality Of Life and Drug Use Assessment in Patients With CAR-T Cells

Self-administered questionnaire EORTC-QLQ C30 (European Organisation for Research and Treatment of Cancer), developed to assess the quality of life of cancer patients, with 30 items. Score ranges from 0 (the worse) to 100 (the best).

Hospices Civils de Lyon

Digestive System Diseases

Esophageal Neoplasms

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Stomach Diseases

Esophageal Cancer

Stomach Cancer

All Drugs and Chemicals

Proton Pump Inhibitors

Enzyme Inhibitors

Long-term use of medications, particularly proton pump inhibitors

Proton pump inhibitor

Jesper Lagergren, MD, PhD

This is a population-based case-control study in all 5 Nordic countries from 1994 onwards. All cases with an esophageal or gastric tumor will be compared with 10 times as many population controls, frequency-matched by age, sex, and calendar year, country. This design offers excellent statistical power, length and completeness of follow-up, quality of data on exposures, outcomes and confounders, and control for confounding.

The project will include a specific study entitled "Long-term medication with proton pump inhibitors and risk of gastric cancer", which is summarized here:

Research question: Medication with proton pump inhibitors (PPI) (e.g., omeprazole and esomeprazole) is one of the most common long-term therapies globally, prompted by its high anti-acidic efficacy and good short-term safety profile. Gastric cancer is the 3rd leading cause of cancer-related mortality globally, responsible for 770,000 deaths each year. There are clear biological mechanisms linking long-term PPI-use with an increased risk of gastric cancer. However, existing research has not been able to provide a definite answer to whether long-term PPI-use is associated with an increased risk of gastric cancer. The reasons are that the literature is hampered by too short follow-up time to assess cancer development, and also insufficient statistical power, lack of population-based design and confounding.

With the availability of nationwide complete medication registries in the Nordic countries, the firsts two starting already in 1994 (Denmark and Finland), we can now, by adding registry data from all Nordic countries together, conduct the first study providing a robust and valid answer to this research question.

Overarching aim This project aims to clarify if (and if so to what extent) long-term PPI-therapy influences the risk of developing gastric adenocarcinoma.

For validation reasons, we will also examine how long-term use of histamine-2-receptor blockers (H2RB) influences the risk of developing gastric adenocarcinoma. These analyses will validate that the findings are specific for PPIs. H2RB are used for the same indications as PPIs, but with a different biological mechanism.

Hypothesis We plan to test the hypothesis that long-term use of PPI (but not H2RB) increases the risk of gastric adenocarcinoma.

Prerequisites

This will be the first project with all prerequisites to provide conclusive answers to the hypotheses above, i.e.:

* Long follow-up (up to 28 years)
* Complete follow-up (by virtue of the nationwide complete Nordic registries)
* Population-based design (which rules out biased selection of cases or controls)
* Superior statistical power (all five Nordic countries participate with nationwide data)
* High-quality data on exposures, outcomes and confounders (thanks to well-maintained and complete nationwide Nordic health data registries)
* Control for confounding factors (available for all participants, both cases and controls)

PROJECT DESCRIPTION

Theory and method

Study design We will conduct a nationwide and population-based multi-national case-control study in the five Nordic countries during the total study period from 1994 through 2022, thus allowing up to 28 years of follow-up. The start of the study period will vary between countries depending on when their national drug registries started, i.e. in 1994 (Denmark), 1994 (Finland), 2002 (Iceland), 2004 (Norway) and 2005 (Sweden).

Participants The study will include all adult residents in Sweden, Denmark, Finland, Iceland and Norway with a first gastric adenocarcinoma diagnosed during the study period according to the national cancer registries. The control participants are selected from the general populations of the five countries and frequency-matched for age, sex, calendar year, and country. The index date for matching is the date of gastric adenocarcinoma diagnosis. For each case of gastric cancer, 10 control participants will be included. Because the controls are matched within each country by age and calendar year, the time-window used to ascertain the exposure will be the same in cases and controls. We will have the same detailed information on all study variables in cases and controls.

Exposure The exposure is long-term PPI-use. Two definitions will be used. The first, high PPI-consumption, is defined as \>180 defined daily doses (DDD) of PPI per year during the time from start of the drug registry or entry in the cohort until the index date. The second definition is cumulative exposure to PPI, defined by the total number of DDDs consumption during the time window of exposure. The DDDs are retrieved from the prescribed drug registries. From a Swedish cohort of 8,276,316 adult individuals of the general population that we use for research purposes, 496,579 (6.0%) were exposed to long-term PPI-use (\>180 DDDs).

The comparison exposure is long-term use of an H2RB (\>180 DDDs), measured using the same two definitions described for PPI, i.e., high H2RB consumption and cumulative exposure. DDDs for H2RB are also retrieved from the prescribed drug registries.

Outcome The study outcome will be gastric adenocarcinoma. Adenocarcinoma represents \>95% of all gastric malignancies. We will not assess rare histologies of gastric malignancy because these have different aetiology, including the potential association with PPI-use. We will also conduct separately sub-analyses of cardia adenocarcinoma and non-cardia adenocarcinoma.

Confounders A confounder is by definition associated with both the exposure and the outcome (and is not in the causal pathway between these).29 The main risk factor for gastric adenocarcinoma is 1) Helicobacter pylori-infection, but also other less strong risk factors might also have some confounding effects in this project, i.e., 2) age (as for most cancer types), 3) sex (a majority of patients with gastric adenocarcinoma are men), 4) calendar year (there have been changes in diagnostic ability of gastric adenocarcinoma), 5) country (there are some variations in incidence rates of gastric adenocarcinoma between the Nordic countries), 6) comorbidity (some severe diseases included in the Charlson comorbidity index might increase the risk of gastric adenocarcinoma), 7) long-term medication with aspirin or non-steroidal anti-inflammatory drugs (such medication may decrease the risk of gastric adenocarcinoma) and 8) long-term medication with statins (could also decrease this risk).

All these 8 variables will be controlled for. Age, sex, calendar year, and country will be controlled for by matching. Helicobacter pylori, comorbidity, long-term medication (\>180 defined DDDs per year) with aspirin or non-steroidal anti-inflammatory drugs and statins will be adjusted for using multivariable logistic regression. Regarding Helicobacter pylori, we will use treatment of this infection as a marker of infection, which is the most complete and valid way to assess presence of this infection in the dataset. For comorbidity we will use the most recent version of the well-validated Charlson comorbidity index.30 We have excellent data of both medication variables from the drug registries.

Data sources For each participant, both cases and all controls, we will collect data from the following nationwide registries in all five countries: 1) Prescribed drug registries, 2) cancer registries, 3) patient registries, 4) cause of death registries and 5) registries of the total population. This will allow data on demographic characteristics (age, sex, calendar year, country), use of all relevant medications (including PPI, H2RB, Helicobacter pylori treatment, aspirin or non-steroidal anti-inflammatory drugs and statins with substance, brand name, ATC-code, formulation, package size, amount, dosage and dates for prescription and dispensation), comorbidity (all diagnoses and surgical procedures), and mortality.

Project organisation

Research team Ten people are directly involved in this project. The project originates and is organised from our research group at Karolinska Institutet (KI). The local team includes 7 people: The chief investigator Jesper Lagergren (main applicant), the biostatistician Giola Santoni, the statistician Jacinth Yan, the postdoctoral researcher Cecilia Radkiewicz, the PhD candidate we hope to recruit, and the administrator Giulia Marras. In addition, we have representatives of each of the four non-Swedish countries included in the project, i.e., associate professor My von Euler-Chelpin (Denmark), professor Joonas Kauppila (Finland), associate professor Helgi Birgisson (Iceland) and associate professor Eivind Ness-Jensen (Norway).

The main roles of these team members are outlined here:

1. Jesper Lagergren will lead the work and the team conducting the work, be responsible for the progress of the project, and be supervisor of the postdoc and PhD candidate.
2. Giola Santoni will guide and supervise in the data complex data management and statistical analyses and co-supervise the PhD candidate.
3. Jacinth Yan will conduct complex data management and analyses.
4. Cecilia Radkiewicz will help with the planning and co-supervise the PhD candidate.
5. The PhD candidate will draft the detailed study protocol, do data management and statistical analyses with support of Giola Santoni, and draft the paper.
6. My von Euler-Chelpin is responsible for the Danish data collection.
7. Joonas Kauppila is responsible for the Finnish data collection.
8. Helgi Birgisson is responsible for the Icelandic data collection.
9. Eivind Ness-Jensen is responsible for the Norwegian data collection.
10. Giulia Marras will help organise the collaboration and administer the project.

Data storage and management Because Danish law does not allow their data to leave the country, data will be stored at a safe server at the governmental agency Statistics Denmark, and managed by remote access. Giola Santoni is responsible for the data management and statistical analyses.

Main applicant The main applicant, Jesper Lagergren, will spend approximately 10% of his work-time for this specific project. He is the chief investigator of this multi-national project.

DATA ANALYSIS AND STATISTICS

Design This will be a population-based case-control study with prospectively collected data on all variables for all cases and controls in the five Nordic countries. The data collection is prospective, which avoids recall bias and selection bias. For each case of gastric adenocarcinoma, 10 control participants from the general populations will be recruited. The control participants will be frequency-matched to the cases regarding age, sex, calendar year and country of residence. The additional possible confounders, i.e., Helicobacter pylori, comorbidity and medication with aspirin or non-steroidal anti-inflammatory drugs as well as statins will be adjusted for by modelling.

Statistical analysis Conditional logistic regression will be used to estimate the relative risk of gastric adenocarcinoma comparing long-term PPI-users with non-users, providing odds ratios with 95% confidence intervals. Three models will be applied: 1) A crude model where only the matching variables are controlled for; 2) an adjusted model additionally adjusted for Helicobacter pylori, comorbidity and medication with aspirin or non-steroidal anti-inflammatory drugs as well as statins, and 3) a model with multivariable adjustment for all 8 confounders listed under 'Confounders' above, which will guarantee that these variables are completely adjusted for. We will also do stratified analyses for each of these 8 confounders. In addition, we will assess whether increased length of PPI-use (\>10 years) among long-term users is associated with higher risk estimates, which would argue in favour of causality. Except for conventional confounding, confounding by indication (particularly protopathic bias) is a special threat to the validity of many pharmaco-epidemiological studies. However, long-term PPI-use is not an indication for gastric adenocarcinoma. Thus, this should not be a problem in the present project.

Statistical power One of the advantages of the project is the excellent statistical power, which is due to inclusion of cases from five entire countries, long and complete follow-up and relatively high prevalence of long-term PPI-users. In order to further optimise the power, we include 10 controls per case, after which further controls will not improve power.31 The main analysis will include all approximately 47,000 cases and 470,000 controls, and sub-analyses of non-cardia adenocarcinoma will include 35,300 cases and 353,000 controls, while the sub-analysis of cardia adenocarcinoma will include 11,700 cases and 117,000 controls. The exposure prevalence of long-term PPI-use is 6% (and 2% for H2RB use). The main analysis has 100% power to verity an odds ratio already of 1.10, and we expect a much stronger association. For the analysis of cardia adenocarcinoma, the study has 94% power to verify an odds ratio of 1.15.

Nordic Gastric and Esophageal Tumor Study

This requires approvals from all institutions delivering the data.

Risk of developing gastric adenocarcinoma using logistic regression providing odds ratios

Risk of developing esophageal cancer using logistic regression providing odds ratios

University of Copenhagen

University of Oulu

Norwegian University of Science and Technology

Reykjavik University

Karolinska Institutet

Professor of Surgery

Substance Related Disorders

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Sarcoma

Drug-Related Side Effects and Adverse Reactions

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Chemically-Induced Disorders

Soft Tissue Sarcoma

Antineoplastic Agents

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

This is a single-arm, two-cohort, open label phase Ib/II trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:

* Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by en expansion phase (II) testing for safety and preliminary evidence of antitumor activity
* Cohort B: single-agent, fixed selinexor dose in the same target population

oral selinexor given once weekly (Cohort A), oral selinexor given BIW (Cohort B)

Selinexor

Imatinib

Cesar Serrano, MD

This is a single-arm, two cohort, open label phase I/II clinical trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:

* Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by an expansion phase (II) testing for safety and preliminary evidence of antitumor activity
* Cohort B: single-agent, fixed selinexor dose in the same target population

Clinical Study Objectives:

Primary clinical study objective

Cohort A:

1.- To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of selinexor in combination with imatinib among unresectable and/or metastatic GIST patients with prior failure to at least imatinib for advanced/metastatic disease.

Cohort B:

1. To evaluate the clinical benefit rate (CBR: CR+PR+SD ≥ 16 wks)

Secondary clinical study objectives (both cohorts A and B)

1. To evaluate the clinical benefit rate (CBR: CR+PR+ SD ≥ 16 wks)
2. To evaluate progression free survival (PFS)
3. To evaluate overall survival (OS)
4. To evaluate the objective response rate (ORR)
5. To evaluate the safety profile according to CTCAE 4.03
6. To compare PFS on selinexor and imatinib and on selinexor in monotherapy with PFS on last prior anti-cancer therapy.

Translational Study Objective - To explore the relationship between GIST genotype and CBR with selinexor and imatinib, and selinexor as single-agent

Pharmacokinetics Study Objective

- To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.

Phase Ib/II, single-arm, two-cohort, non-randomized, open-label, multicenter, national clinical trial, single agent, combinations products

Selinexor as Single Agent and With Imatinib in Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (SeliGIST)

A Multicenter, Phase Ib/II Trial of Selinexor as a Single Agent and in Combination With Imatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GISTs)

The final publication of the trial results will be written by the international coordinating investigators on the basis of the final analysis performed. The draft manuscript will be reviewed by the coordinating investigators and other co-authors. After revision the manuscript will be sent to a major scientific journal. Results obtained in the different strata may be separately published.

Maximum tolerated dose (MTD) is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT) during the first 28 days of treatment. Dose escalation cohort (Phase 1b) seeks to determine the frequency and characteristics of DLTs of the selinexor plus imatinib combination at each dose level during the first cycle of therapy. Phase Ib will be carried out in standard 3+3 format, based on the toxicities found during the first cycle of therapy.

Clinical benefit rate (CBR) is defined as CR+PR+SD ≥ 16 wks

Efficacy measured by PFS assessed by median time. PFS is defined as the time between the date of first experimental treatment dose and the date of disease progression (according to RECIST 1.1 criteria).

Efficacy measured by OS. OS is defined as the time between the date of first experimental treatment dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive, or when the last enrolled patiens are followed up to for 12 months, whichever is early.

Efficacy measured by ORR. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 and Choi criteria).

Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.

Toxicity will be graded and tabulated by using CTCAE 4.03.

GIST genotype determinations and its correlation with response to the treatment with selinexor and imatinib in terms of clinical benefit (CBR).

To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.

Number of patient with CBR ≥ 30% lasting ≥ 16 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Quality Of Life and Drug Use in Patients With CAR-T Cells	NCT04914091	Patients With D...	Semi-structured...	18 Years -	Hospices Civils de Lyon
Nordic Gastric and Esophageal Tumor Study	NCT05688761	Cancer of Stoma... Cancer of the E... Drug Use	Proton pump inh...	18 Years -	Karolinska Institutet
Selinexor as Single Agent and With Imatinib in Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (SeliGIST)	NCT04138381	Maximum Tolerat... GIST Metastatic Adul... Drug Toxicity Drug Use	Selinexor Imatinib	18 Years -	Grupo Espanol de Investigacion en Sarcomas
Nordic Gastric and Esophageal Tumor Study	NCT05688761	Cancer of Stoma... Cancer of the E... Drug Use	Proton pump inh...	18 Years -	Karolinska Institutet

Spots Global Cancer Trial Database for drug use

Every month we try and update this database with for drug use cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for drug use

Every month we try and update this database with for drug use cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for drug use cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.