Clinical trial NCT04459234: Prospective Multicentre Study of the Use of Ketamine in the Treatment of Refractory Chronic Pain in the French CLCC
Official title: KETACANCER: Prospective Multicentre Study of the Use of Ketamine in the Treatment of Refractory Chronic Pain in the French CLCC
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Chronic Pain
Neuropathic Pain
Opioid Use
Keywords: Cancer
Palliative care
Ketamine
Chronic pain
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2020-07-07
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a prospective, multicentre study, considered as " non-RIPH (Recherche n'Impliquant pas la Personne Humaine ". Indeed, the patient's participation in the study and the completion of the various questionnaires has no impact on patient's safety and is not likely to change his/her management. The treatment will be conducted according to the standard practices of each participating site (continuous or discontinuous protocol, dosage, rhythm of administration, monitoring, etc.). The questionnaires and scales used in this study are part of the recommended tools for monitoring this population.

Brief summary: The primary objective of this study is to describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of indication (neuropathic sequelae pains, morphine additional effect or morphine withdrawal, intensity, localisation...) and administration protocol (route, posology, duration, administration sequence, premedication).

The secondary objectives are to evaluate in the context of cancer, the analgesic efficacy, the tolerance profile (biological and clinical toxicities) and the quality of life, including anxiety and depression.

In addition, the described parameters will be evaluated as safety and efficacy predictive factors of the Ketamine in oncology.

Detailed description: Almost 382,000 new cancers have been diagnosed in France in 2018. Regular progresses in their management have improved the overall survival of patients, sometimes with sequelae that may be particularly painful. Thus for 20 to 45% of patients treated for breast cancer, pain persists 5 years later.

If remission is a regularly reached target, cancer was also the cause of 157,000 deaths in 2018 in France, preceded by months or years of progression of a chronic disease that regularly causes pain. Pain during cancer (chronic cancer pain for CIM-11) remains a frequent symptom, and its prevalence has slightly changed during the last 20 years.

In the European EPIC study, carried out in 2006, 76% of the cancer patients (and 62% of French patients) presented moderate to severe pains linked to cancer, daily for more than half of them.

Even when identified, chronic cancer pain is still under-treated in 25 to 60% of cases worldwide, including in the most developed countries.

When well-managed, pain's management now allows the relief of almost 80% of patients. Pain's management is based in particular on a precise and adapted use of the different opioids through different routes of administration (oral, transdermal, trans-mucosal, parenteral, etc.).

A neuropathic component of pain exists in almost a third of cases and may require specific treatments when opioids are insufficient. In all cases, the treatment is integrated into a multidisciplinary management, in connection with the ongoing oncological treatments, the loco-regional treatments available (radiotherapy, interventional radiology, etc.) and with an adapted psychosocial management.

Ketamine is an NMDA receptor antagonist (N-Methyl-D-Aspartate) indicated as a high dose anesthetic. It is used in the context of peri-operative pain for its anti-hyperalgesic properties. These properties have led to its use also in palliative care (outside the marketing authorization \[AMM\]) to treat hyperalgesia linked to the use of high-doses of opioids, as well as depression. For non-cancer pains, ketamine is widely used by centres and consultations specialized in refractory chronic pain management in different pains not relieved by standard treatments: neuropathic pain, fibromyalgia, etc., or even in opioids weaning aid.

The bibliographic data are not homogeneous and of low quality. Despite the weakness of the available data, ketamine is widely used in France in chronic pain in situation of therapeutic impasse. The protocols used vary according to the prescribers and services practices: venous route in general, sometimes subcutaneous or even oral; doses varying from 30 to 200 mg / day, infusion duration varying from a few hours to several days, discontinuous administration by cycle or continuous administration, etc.

Current knowledge is too limited in oncology to have a consensus on the use of ketamine :

* Often retrospective studies with heterogeneous treatment protocols;
* Studied populations also heterogeneous, with insufficiently documented indications;
* Staff not able to answer adequately the questions raised. This situation largely explains the heterogeneity of the Ketamine practices of use in oncology

It is essential to draw up an inventory of the ketamine use by the French CLCCs pain teams and to identify the profile of patients in whom i) the treatment is ineffective and must be avoided regarding toxicities ii) the potential efficacy required further investigations. Built on a methodology close to the OKAPI study, the KETACANCER study will enable to compare indirectly the results of the two studies.

To do this, it is proposed to conduct the KETACANCER prospective study in a precise population defined a priori, and corresponding to the following indications:

* Neuropathic sequelae pain
* Additional effect of morphine
* Morphine weaning.

Eligibility criteria: Inclusion Criteria:

* Patient at least 18 years old at the day of consenting to the study
* Patient followed for a solid tumour or a hematological malignancy (treated or under treatment)
* Patient presenting cancer chronic pain or post cancer treatment pain
* Patient followed by a CLCC's intractable chronic pain consultation or centre
* Patient with an indication of 1st Ketamine course:
* Analgesic treatment of cancer chronic pain
* Analgesic treatment for a post-cancer treatment chronic pain
* Help for withdrawal from opioid treatment prescribed for a chronic cancer pain
* Patient not previously treated by Ketamine
* Patient covered by a medical insurance
* Patient and/or family did not decline data collection after complete information (information sheet)

Exclusion Criteria:

* Patient presenting chronic pains not related to cancer or its treatments
* Patient with a proven psychotic history
* Patient who is not fluent enough in French

Primary outcomes:
measure: Describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of indication
timeFrame: Up to 3 months after inclusion
measure: Describe the administration practices of the antalgic Ketamine in French CLCC (Centre de Lutte Contre le Cancer) in terms of administration protocol
timeFrame: Up to 3 months after inclusion
Secondary outcomes:
measure: Evaluate in the context of cancer the antalgic efficacy
timeFrame: Up to 3 months after inclusion
measure: Evaluate in the context of cancer the antalgic efficacy
timeFrame: Up to 3 months after inclusion
measure: Evaluate in the context of cancer the antalgic efficacy
timeFrame: Up to 3 months after inclusion
measure: Evaluate in the context of cancer the tolerance profile
timeFrame: Up to 3 months after inclusion
measure: Evaluate in the context of cancer the quality of life including anxiety and depression
timeFrame: Up to 3 months after inclusion
measure: Evaluate in the context of cancer the quality of life including anxiety and depression
timeFrame: Up to 3 months after inclusion
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Institut de Cancérologie de Montpellier
city: Paris
country: France
facility: Institut Curie
city: Reims
country: France
facility: Institut Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Toulouse
country: France
facility: Institut Universitaire du Cancer (IUCT)
city: Vandoeuvre les nancy
country: France
facility: Institut de Cancérologie de Lorraine Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Leon Berard
name: Gisèle CHVETZOFF, MD
role: PRINCIPAL_INVESTIGATOR
References: