The Kinetics of Endocannabinoids in Patients With Chemotherapy Induced Peripheral Neuropathy by Using Medical Cannabis.

Study Overview
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Brief Summary
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Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological cancer treatment complication. Medical cannabis is indicated in Israel for the treatment of chronic pain, spasticity and for the control of pain and other symptoms in patients with cancer. The proposed study aims are to study about the changes in level of endocannabinoids following continuous exposure to phytocannabinoids and about the long-term effect of medical cannabis on CIPN.

Detailed Description
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This will be a self-titrated, open-label design study. Subjects who begin taxanes or oxaliplatine therapy and were diagnosed with CIPN will be recruited to the study. After providing their written informed consent, the study physician obtained a medical history, demographic details and conducted a physical examination. During the current study, baseline period for CIPN evaluation will be 2 weeks, while patients will fill several questionnaires. Baseline CIPN will be evaluating by DN4 and BPI questionnaires. EQ-5D and PSQI will be filled for baseline Quality of life (QOL) and sleepiness status, accordingly.

Official Title
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The Kinetics of Endocannabinoids in Patients With Chemotherapy Induced Peripheral Neuropathy by Using a Portable Metered-Dose Cannabis Inhaler

Conditions
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Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: medical cannabis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age above 18 years and below 80 years old. 2. Pathology of Breast or GI malignancies. 3. Treatment with Taxans (Taxol/ Taxotere) or Oxaliplatin for adjuvant treatment or metastatic disease. 4. Estimated life expectancy ≥ 6 months. 5. Performance status ≤1 (ECOG classification). 6. Sign of written informed consent. 7. CIPN is examined during the chemotherapy treatment DN4 score must be above 4 (and by physician decision) for more than one week. 8. Patient with adequate liver/renal function at screening as described: Creatinine clearance >30 ml/min as calculated by Cockcroft-Gault Equation. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN. 9. Patients who suffer from pain although using a stable analgesic treatment' at least 14 days before entering the trial (no limitation for the use of the analgesic). 10. Patient possessed a valid license from the Israeli Ministry of Health to receive medicinal cannabis. 11. Patient is able and willing to comply with study requirements. 12. Patient agrees to use only medical cannabis provided by study team until the end of study period. 13. Patient has not undergone major surgery in the month prior to the study start. 14. Patient agrees not to participate in other interventional clinical trial during the study participation. Exclusion Criteria: 1. Use of cannabis or synthetic cannabinoids in the last two weeks (urine test for cannabinoids are positive). 2. Patient with known or past substance abuse. 3. Patients with major psychiatric disorders (e.g. schizophrenia, dementia, and intellectual disabilities). 4. Patients with first degree siblings under the age of 30 years old with psychiatric disorders. 5. Patients with uncontrolled diabetes mellitus, cardiovascular, or convulsive disorders according to investigator. 6. Patients with sensitivity to cannabis or cannabinoids. 7. Patients with known neuropathic pain due to diabetes or other diseases. 8. Patients with severe respiratory disease. 9. Patients with brain metastases or brain tumors may participate if completed radiotherapy treatment at least 14 days prior to signing the informed consent and last imaging did not show any worsening. 10. Female subjects who are pregnant, lactating, or want to get pregnant during the study period and one month following the study. Male subjects who want their partner to get pregnant during the study period and one month following the study. 11. Females of childbearing potential or males whose partners with childbearing potential and did not use adequate contraceptives 28 days prior to study start or during the study. 12. Other life-threatening medical conditions that disqualify the patient from participating in the study, according to the Primary Investigator's judgment. 13. Anticipated alcohol or barbiturate use during the study period. 14. Participation in other clinical trials during the last month. 15. Subjects who are using one of the following medications: opiates (Primidone, Phenobarbitol, Arbamazepine, Rifampicin, Rifabutin, Troglitazone and Hypericum perforatum). 16. Patient who has undergone a major surgery a month prior to study start.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Syqe Medical Cannabis inhaler is approval medical device in Israel , this is only Basic science study with main purpose to learn more about the kinetics of endocannabinoids .
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: medical cannabis<br>All patients will start with 250mcg cannabis flos BID and will follow the titration plan of dose modification according to CIPN relief and adverse events. Maximum dose of 2,000mcg per day is prescribed at the end of titration period, which is continuous for 15 days (about 2 weeks).On 10 weeks visit all patients will be discontinued from the treatment. In case of worsening of neuropathy at any point during the 4 weeks of FU, patients might be able to restart with inhaled MC treatment for no more than 4 weeks. Total treatment in this study will be for no more than 14 weeks. | Drug: medical cannabis<br>* inhalation by using a Portable Metered-Dose Cannabis Inhaler<br>* Other names: medical marijuana;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the level of 150 different endocannabinoids. | Circulating endocannabinoids concentrations . | Determined on blood samples collected during the 4 months of participation in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from the baseline of neuropathic pain during medical cannabis treatment . | Neuropathic pain detected by DN4 questionnaire . | during 4 months of participation in the study | 
| Changes in Quality of life by FACT-GOG-Ntx | Changes of Quality of life will be evaluated by Functional Assessment of Cancer Therapy - Gynecologic Oncology Group-Neurotoxicity ( FACT-GOG-Ntx) questionnaire | This exam will be performed every visit.during 4 months of participation in the study | 
| Changes in Quality of life by BPI | Changes of Quality of life will be evaluated by BRIEF PAIN INVENTORY (BPI) tool. | This exam will be performed every visit.during 4 months of participation in the study |