Symptoms and General Pathology

All Conditions

Neoplasms

Behaviors and Mental Disorders

Rare Diseases

Recurrence

Glioblastoma

Disease Progression

Astrocytoma

Disease Attributes

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Quality of Life

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Immunomodulating Agents

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care

Re-resection

Re-irradiation with single dose, fractionated, or hypofractionated radiation of the recurrent tumor

Re-irradiation

Experimental phase I therapy with oncolytic virotherapy or immunotherapy (this list is not exhaustive)

Experimental therapy

Best supportive care, focused on alleviating symptoms

Best supportive care

Jasper Gerritsen, MD PhD

Arnaud Vincent, MD PhD

Mitchel Berger, MD PhD

Brian Nahed, MD PhD

Steven De Vleeschouwer, MD PhD

Christine Jungk, Dr. med.

Arthur Wagner, MD

Jasper Gerritsen, MD

Marike Broekman, MD PhD

Philippe Schucht, MD PhD

Previous evidence has indicated that resection for recurrent glioblastoma might benefit the prognosis of these patients in terms of overall survival. However, the demonstrated safety profile of this approach is contradictory in the literature and the specific benefits in distinct clinical and molecular patient subgroups remains ill-defined. The aim of this study, therefore, is to compare the effects of resection and best oncological treatment for recurrent glioblastoma as a whole and in clinically important subgroups.

This study is an international, multicenter, prospective observational cohort study. Recurrent glioblastoma patients will undergo tumor resection or best oncological treatment at a 1:1 ratio as decided by the tumor board. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks after surgery and 2) overall survival. Secondary endpoints are: 1) progression-free survival (PFS), 2) NIHSS deterioration at 3 months and 6 months after surgery, 3) health-related quality of life (HRQoL) at 6 weeks, 3 months, and 6 months after surgery, and 4) frequency and severity of Serious Adverse Events (SAEs) in each arm. Estimated total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

This is an international, multicenter, prospective, cohort study. Eligible patients are operated or receive best oncological treatment with a 1:1 ratio with a sequential computer-generated random number as subject ID. Intraoperative mapping techniques and/or surgical adjuncts can be used in both treatment arms to ensure the safety of the resection (to minimize the risk of postoperative deficits).

Study patients undergo tumor re-resection or receive best oncological treatment and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) and MRC (Medical Research Council) scale. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. This neurolinguistic test-battery is the result of a consensus between the participating centers. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Overall patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system for comorbidities. Health-related quality of life (HRQoL) will be assessed with the EQ-5D questionnaire and the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study, including follow-up, will be 5 years.

The primary study objective is to evaluate the safety and efficacy of re-resection versus best oncological treatment (neurological morbidity and overall survival) in recurrent glioblastoma patients as expressed by NIHSS scores and survival data. Secondary study objectives are to study the overall progressive-free survival (PFS), long-term neurological morbidity (3 months and 6 months postoperatively), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resection versus best oncological treatment as expressed by progression on follow up MRI scans based on the RANO criteria24 for tumor progression; NIHSS scores, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs.

Patients will be recruited for the study from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals of the ENCRAM Research Consortium, located in Europe and the United States.

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2302)

Time from diagnosis to death from any cause

NIHSS deterioration of 1 point or more at 6 weeks after surgery

NIHSS deterioration of 1 point or more at 3 months after surgery

NIHSS deterioration of 1 point or more at 6 months after surgery

Time from diagnosis to disease progression (occurrence of a new tumor lesions with a volume greater than 0.175 cm3, or an increase in residual tumor volume of more than 25%) or death, whichever comes first

Residual tumor volume of the contrast-enhancing and non-contrast enhancing part, as assessed by a neuroradiologist on postoperative MRI scan (T1 with contrast and FLAIR sequences) using manual or semi-automatic volumetric analyses (Brainlab Elements iPlan CMF Segmentation, Brainlab AG, Munich, Germany; or similar software)

Quality of life as assessed by the EORTC QLQ C30 questionnaire

Quality of life as assessed by the EORTC QLQ BN20 questionnaire

Quality of life as assessed by the EQ-5D questionnaire

Serious Adverse Events within 6 weeks postoperatively

Haaglanden Medical Centre

Universitaire Ziekenhuizen KU Leuven

University Hospital Heidelberg

Technical University of Munich

Insel Gruppe AG, University Hospital Bern

Massachusetts General Hospital

University of California, San Francisco

Jasper Gerritsen

The patients in the control group will have a "classic" course of treatment. They will receive -An educational assessment consisting on evaluating the patient's educational needs.

* Group workshops entitled "Disease and drugs", "Dietary and sports activity", "Psychology Workshop" during which the patient will be able to participate in order to get all the information he needs.
* Individual therapeutic education sessions to specifically and personally highlight certain non-pharmaceutical educational needs identified at the time of the educational assessment.

Moreover, in the control arm, a systematic "short pharmaceutical interview" with an average duration of 15 minutes will be proposed to patients at the initiation of treatment, at D15 after the prescription (considered as the date of inclusion) at M1 and then every 3 months (M3, M6, M9 and M12):

The patients will receive the same course of treatment as in the control group, including the D0 short pharmaceutical interview, with the same prerogatives of acceptance or rejection of participation in the TPE program. Short pharmaceutical interviews from D15 to M12 will be replaced by long pharmaceutical consultations of 30 to 60 minutes. The latter consisting in a full clinical medication review and incorporating the pedagogic aspects addressed in the short pharmaceutical interviews but for all therapeutic drugs taken by the patient. Additional consultations are possible on the request of the oncologist and/or patient. The consultations carried out at the request of the oncologist and/or the patient will be counted The first part of the pharmaceutical consultation focuses on a complete clinical medication review including Establishment of the patient profile: medical history, drug allergies and intolerance, comorbidities, age, understanding capacities, organizational capacity

The first part of the pharmaceutical consultation focuses on a complete clinical medication review, the effective use of drugs will be discussed with the patient.

Study of health behaviors Concerning self-medication and alternative medicine Addictions Drug adherence List and grade (NCI version 4) of clinical signs and laboratory abnormalities The biological data will be obtained Clinical signs will be obtained from patient questioning The second part of the consultation is to achieve firstly a pharmaco-therapeutic analysis of the treatment in order to detect problems with drugs as classified by the French Society of Clinical Pharmacy The third step consists on providing "pharmaceutical interventions" following the pharmaco-therapeutic analysis (18).

These pharmaceutical interventions might concern the prescribers, the other caregivers, or the patient himself. T

Pharmaceutical Consultations

No Pharmaceutical Consultations

Stéphane HONORE

Urielle DESALBRES

The improvement of the care pathway of oncology patients through Clinical Pharmacy activities for outpatients (such as pharmaceutical consultation) should be implemented and evaluated.

In order to improve the care pathway of patients on anticancer oral therapies, The investigators suggest in this research project to integrate into the medical care a "Clinical Pharmacy follow-up" for the patient at the hospital in the form of "pharmaceutical consultations". These pharmaceutical consultations carried out in coordination with the hospital clinical teams also aim to make the link between the hospital and community pharmacists.

The improvement of the care pathway of oncology patients through Clinical Pharmacy activities for outpatients (such as pharmaceutical consultation) should be implemented and evaluated.

In order to improve the care pathway of patients on anticancer oral therapies, the investigators suggest in this research project to integrate into the medical care a "Clinical Pharmacy follow-up" for the patient at the hospital in the form of "pharmaceutical consultations". These pharmaceutical consultations carried out in coordination with the hospital clinical teams also aim to make the link between the hospital and community pharmacists. These pharmaceutical consultations were initiated in Marseille and Grenoble University Hospitals in order to know the special needs of patients under oral chemotherapies. However, the impact of these pharmaceutical consultations in a population of patients receiving ambulatory oral therapy remains unknown and needs to be evaluated using objective criteria such as the rate of adverse events which the consequences are considerable both for the patient and the society.

These observations prompted us to establish a randomized controlled study with the objective of assessing the impact of the Clinical Pharmacy consultations in cancer patients treated with oral anti-cancer therapies on the general care management: occurrence of serious adverse events (primary outcome).

This bicenter, prospective, randomized, placebo-controlled, open-label, two-parallel group study is performed to assess the efficacy of pharmaceutical consultations in the experimental group (full clinical medication review) and pharmaceutical interviews in the control group (Patient Therapeutic Education for oral anticancer drugs only). Depending on the result of the randomization the patient will find himself in one of those 2 parallel arms:

* Control group: standard course + short pharmaceutical interviews (therapeutic education)
* Experimental group: standard course + long pharmaceutical consultations (including full clinical medication review and therapeutic education)

Control group: therapeutic education through short pharmaceutical interviews

The patients allocated in the control group will have a "classic" course of treatment. They will receive the best medical care and will be offered to participate in the therapeutic education program in place in the participating centers including:

* An educational assessment consisting on evaluating the patient's educational needs.
* Group workshops entitled "Disease and drugs", "Dietary and sports activity", "Psychology Workshop" during which the patient will be able to participate in order to get all the information he needs.
* Individual therapeutic education sessions to specifically and personally highlight certain non-pharmaceutical educational needs identified at the time of the educational assessment.

Moreover, in the control arm, a systematic "short pharmaceutical interview" with an average duration of 15 minutes will be proposed to patients at the initiation of treatment, at D15 after the prescription (considered as the date of inclusion) at M1 and then every 3 months (M3, M6, M9 and M12):

* Dosage, including the maximum dosage for modular taken drugs
* Duration of treatment
* User precautions
* The necessary information to drug use
* Any special precautions to be taken and any information relevant to the good understanding of the treatment by the patient
* Biological analyzes necessary for the initiation, monitoring, and pursuit of certain treatments

Experimental group: Clinical Pharmacy through Long Pharmaceutical Consultations In this experimental group, patients will receive the same course of treatment as the patients in the control group, including the D0 short pharmaceutical interview, with the same prerogatives of acceptance or rejection of participation in the TPE program. Short pharmaceutical interviews from D15 to M12 will be replaced by long pharmaceutical consultations of 30 to 60 minutes. The latter consisting in a full clinical medication review and incorporating the pedagogic aspects addressed in the short pharmaceutical interviews but for all therapeutic drugs taken by the patient. Additional consultations are possible on the request of the oncologist and/or patient. The consultations carried out at the request of the oncologist and/or the patient will be counted.

The first part of the pharmaceutical consultation focuses on a complete clinical medication review including:

* Establishment of the patient profile: medical history, drug allergies and intolerance, comorbidities, age, understanding capacities, organizational capacity...
* Establishment of the list of current treatments (cancer treatment, treatment of comorbidities, self-medication, other products). The effective use of drugs will be discussed with the patient.
* Study of health behaviors:

  * Concerning self-medication (reasons, active ingredients, doses, etc.) and alternative medicine
  * Addictions (smoking, alcohol...)
  * Drug adherence
* List and grade (NCI version 4) of clinical signs and laboratory abnormalities:

  * The biological data will be obtained on the basis of biological test results addressed to the oncologist and all other test results provided by the patient
  * Clinical signs will be obtained from patient questioning The second part of the consultation is to achieve firstly a pharmaco-therapeutic analysis of the treatment (level 3 pharmaceutical analysis according to the criteria of the French Society of Clinical Pharmacy) in order to detect problems with drugs as classified by the French Society of Clinical Pharmacy (18).

The third step of the consultation consists on providing "pharmaceutical interventions" following the pharmaco-therapeutic analysis (18).

These pharmaceutical interventions might concern the prescribers, the other caregivers, or the patient himself. These interventions will be done in the absolute respect for the French Code of Public Health. All these interventions will be documented, tracked, and evaluated, particularly in terms of acceptance by prescribers.

Sample size Both centers have the necessary number of patients needed to ensure the proper recruitment required for the study.

The annual throughput of the AP-HM is about 300 patients. Targeted diseases as part of this research project are gastrointestinal tumors (GIST, colorectal), neuroendocrine, renal, gynecological, urological (prostate) and skin (melanoma) cancers. The annual throughput of Grenoble University Hospital is more than 70 patients. Targeted diseases are renal tumors, breast and colorectal cancers.

The number of subjects to be included required is determined from the primary endpoint, namely the rate of adverse events of grade III-IV. Data from the current practice in the main center (AP- HM) and from the literature estimate this rate at 35%.

The majority of adverse events related to drugs being preventable, the investigators estimate a decrease of 20 points in this rate in the experimental arm, that is to say a rate of 15%. 166 subjects (83 per group) are needed for a power of 90% and an alpha risk of 5%. To compensate the potential lost of the out of sights (estimated around 15%), the investigators will include 190 subjects in total.

The sample size was determined to obtain 90% power to detect a 20 percent difference in between the 2 groups, as this difference is considered to be clinically significant. In accordance with previous studies (26-31), the investigators hypothesized that the occurrence of the primary endpoint will be at 35% in the control group. With the threshold for statistical significance set at a p-value of 0.05 (two-sided alpha), these calculations showed that 166 patients are needed (83 per group). Assuming that potentially 15% of patients will be lost to follow-up, a total of 190 individuals need to be included.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)	NCT06283927	Glioblastoma Glioblastoma Mu... Glioblastoma, I... Glioblastoma Mu... Glioblastoma Mu... Recurrent Gliob... Astrocytoma, Ma... Astrocytoma of ...	Re-resection Temozolomide Lomustine Re-irradiation Experimental th... Best supportive...	18 Years - 90 Years	Erasmus Medical Center
Impact of Clinical Pharmacy Consultations in Patients With Cancer Treated With Oral Anti-cancer Therapies on the Rate of Serious Adverse Events	NCT02733965	Oral Anticancer...	Pharmaceutical ... No Pharmaceutic...	18 Years -	Assistance Publique Hopitaux De Marseille

Spots Global Cancer Trial Database for serious adverse events