Cannabidiol for Prevention of Chemotherapy-induced Peripheral Neuropathy

Study Overview
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Brief Summary
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This protocol describes a phase II trial investigating the efficacy of CBD in paclitaxel- and oxaliplatin-induced peripheral neuropathy. The trial uses multiple assessments such as validated PRO-questionnaires and multifrequency vibrometry.

Detailed Description
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Chemotherapy induced peripheral neuropathy (CIPN) is among the most feared side effects to cancer treatment. The development of CIPN can lead to omission or even discontinuation of antineoplastic drugs, possibly affecting efficacy of cancer treatment. There is a lack of knowledge about the natural course of CIPN and to this date, there are no available methods for the early detection of CIPN. With no effective prevention or treatment options, the condition has severe impact on patient quality of life and healthcare expenditure.

Official Title
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A Phase II Trial of Cannabidiol for Prevention of Chemotherapy-induced Peripheral Neuropathy in Patients Receiving Oxaliplatin or Paclitaxel Based Chemotherapy

Conditions
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Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: Cannabidiol 100 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age. A diagnosis of cancer. Fulfill criteria for starting chemotherapy. Scheduled to undergo at least 6 courses of paclitaxel or 4 courses of oxaliplatin based chemotherapy. If not postmenopausal (defined as no menses for 12 months without an alternative medical cause), women will have use effective anti-contraception (using definitions in the CTFG*-Recommendations related to contraception and pregnancy testing in clinical trials) and submit to a monthly pregnancy test (blood test). Exclusion Criteria: Unable to complete PRO-measurements. Previously received taxanes or platinum-based chemotherapy. If using any antiepileptic or antidepressant medicine (ATC: N03A or N06A). Treatment must be stable (no changes in dosing in last 30 days) prior to inclusion. However, any treatment with Clobazam (N05BA09) is not allowed due to major interaction with cannabidiol. Use of cannabinoids. If in use, treatment must be stopped 4 days prior to inclusion. Hypersensitivity reactions towards Ascorbylpalmitat or Triglycerides (medium-chain) Baseline transaminase level must not be above 3 times the Upper Limit of Normal (ULN) at study beginning. Women who are breastfeeding. Concomitant treatment with strong inducers of CYP3A4 and/or strong inducers of CYP2C19. CTFG: The Heads of Medicines Agencies commissioned Clinical Trials Facilitation Group under the European Union's clinical trials directive 2001/20.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol<br>Patients will receive cannabidiol in conjunction with their standard chemotherapy treatment | Drug: Cannabidiol 100 MG/ML<br>* Patients receive cannabidiol before and after treatment with chemotherapy<br>* Other names: CBD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Acute Neuropathic Symptoms from baseline and during 1. course chemotherapy. | Difference in the North Central Cancer Treatment Group (NCCTG)- acute-CIPN Questionnaire from baseline compared to 3-5 days after initiation of chemotherapy course no. 1. The Questionnaire contains single items questions, answerable on a 0-10 numeric scale, 0 corresponds to no symptoms and 10 worst possible symptoms. | up to 5 days | 
| Difference in Vibrograms from baseline and during 1. course chemotherapy. | Difference in the Vibrograms from baseline compared to 3-5 days after initiation of chemotherapy course no. 1. | up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in baseline vibrograms of patients treated with CBD compared to vibrograms at follow-up 3 mo. after the end of the 6th course of chemotherapy or the last course of chemotherapy (if before course no. 6). | For patients receiving paclitaxel-based chemotherapy | through study completion, an average of 1 year and 6 months | 
| Difference in baseline vibrograms of patients treated with CBD compared to vibrograms at follow-up 3 mo. after the end of the 4th course of chemotherapy or the last course of chemotherapy (if before course no. 4) | For patients receiving oxaliplatin-based chemotherapy | through study completion, an average of 1 year and 6 months | 
| Difference in CIPN from baseline to after chemotherapy course no. 3 | For patients receiving paclitaxel: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy Questionnaire Module (EORTC-QLQ-CIPN20) from baseline compared to after chemotherapy course no. 3. The EORTC-QLQ-CIPN20 is a validated 20-item patient reported outcome questionnaire. Items are answered on a scale from 1-4. 1 corresponds to no symptoms and 4 to a lot of symptoms. A summary score will be calculated based on items 1-18, Min. value 18, Max. value 72. | through study completion, an average of 1 year and 6 months | 
| Difference in CIPN from baseline to after chemotherapy course no. 6 | For patients receiving paclitaxel: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy Questionnaire Module (EORTC-QLQ-CIPN20) EORTC-QLQ-CIPN20 from baseline compared to after chemotherapy course no. 6. The EORTC-QLQ-CIPN20 is a validated 20-item patient reported outcome questionnaire. Items are answered on a scale from 1-4. 1 corresponds to no symptoms and 4 to a lot of symptoms. A summary score will be calculated based on items 1-18, Min. value 18, Max. value 72. | through study completion, an average of 1 year and 6 months | 
| Difference in CIPN from baseline to 1. follow-up (PAC) | For patients receiving paclitaxel: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy Questionnaire Module (EORTC-QLQ-CIPN20) from baseline compared to 1. Follow-up, 3 mo. after chemotherapy. The EORTC-QLQ-CIPN20 is a validated 20-item patient reported outcome questionnaire. Items are answered on a scale from 1-4. 1 corresponds to no symptoms and 4 to a lot of symptoms. A summary score will be calculated based on items 1-18, Min. value 18, Max. value 72. | through study completion, an average of 1 year and 9 months | 
| Difference in CIPN from baseline to after chemotherapy course no. 2 | For patients receiving oxaliplatin: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy Questionnaire Module (EORTC-QLQ-CIPN20) from baseline compared to after chemotherapy course no. 2. The EORTC-QLQ-CIPN20 is a validated 20-item patient reported outcome questionnaire. Items are answered on a scale from 1-4. 1 corresponds to no symptoms and 4 to a lot of symptoms. A summary score will be calculated based on items 1-18, Min. value 18, Max. value 72. | through study completion, an average of 1 year and 6 months | 
| Difference in CIPN from baseline to after chemotherapy course no. 4 | For patients receiving oxaliplatin: Difference in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy Questionnaire Module (EORTC-QLQ-CIPN20) from baseline compared to after chemotherapy course no. 4. The EORTC-QLQ-CIPN20 is a validated 20-item patient reported outcome questionnaire. Items are answered on a scale from 1-4. 1 corresponds to no symptoms and 4 to a lot of symptoms. A summary score will be calculated based on items 1-18, Min. value 18, Max. value 72. | through study completion, an average of 1 year and 6 months | 
| Difference in CIPN from baseline to 1. follow-up (OX) | For patients receiving oxaliplatin: Difference in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy Questionnaire Module (EORTC-QLQ-CIPN20) from baseline compared to 1. Follow-up, 3 mo. after chemotherapy. The EORTC-QLQ-CIPN20 is a validated 20-item patient reported outcome questionnaire. Items are answered on a scale from 1-4. 1 corresponds to no symptoms and 4 to a lot of symptoms. A summary score will be calculated based on items 1-18, Min. value 18, Max. value 72. | through study completion, an average of 1 year and 9 months | 
| Difference in QoL from baseline to after chemotherapy course no. 3 | For patients receiving paclitaxel: Difference in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) from baseline compared to after chemotherapy course no. 3. The EORTC-QLQ-C30 is a fully validated and internationally accredited 30-item questionnaire measuring 16 subscales. Items are answered on a scale from 1-4, 1 corresponds to no symptoms and 4 to a lot of symptoms. We calculate and report on all 16 subscales. | through study completion, an average of 1 year and 6 months | 
| Difference in QoL from baseline to after chemotherapy course no. 6. | For patients receiving paclitaxel: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) from baseline compared to after chemotherapy course no. 6. The EORTC-QLQ-C30 is a fully validated and internationally accredited 30-item questionnaire measuring 16 subscales. Items are answered on a scale from 1-4, 1 corresponds to no symptoms and 4 to a lot of symptoms. We calculate and report on all 16 subscales. | through study completion, an average of 1 year and 6 months | 
| Difference in QoL from baseline to after chemotherapy course no. 2 | For patients receiving oxaliplatin: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) from baseline compared to after chemotherapy course no. 2. The EORTC-QLQ-C30 is a fully validated and internationally accredited 30-item questionnaire measuring 16 subscales. Items are answered on a scale from 1-4, 1 corresponds to no symptoms and 4 to a lot of symptoms. We calculate and report on all 16 subscales. | through study completion, an average of 1 year and 6 months | 
| Difference in QoL from baseline to after chemotherapy course no. 4 | For patients receiving oxaliplatin: Difference in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) from baseline compared to after chemotherapy course no. 4. The EORTC-QLQ-C30 is a fully validated and internationally accredited 30-item questionnaire measuring 16 subscales. Items are answered on a scale from 1-4, 1 corresponds to no symptoms and 4 to a lot of symptoms. We calculate and report on all 16 subscales. | through study completion, an average of 1 year and 6 months | 
| Difference in the Vibrograms after chemotherapy course 1 | For patients receiving paclitaxel: Difference in the Vibrograms from baseline compared to after chemotherapy course no. 6. | through study completion, an average of 1 year and 6 months | 
| Difference in the Vibrograms after chemotherapy course 2 | For patients receiving oxaliplatin: Difference in the Vibrograms from baseline compared to after chemotherapy course no. 4. | through study completion, an average of 1 year and 6 months | 
| Dose reductions | Number of patients needing a dose reduction in accordance with national Danish treatment guidelines(reasons for discontinuation will be registered). | through study completion, an average of 1 year and 6 months | 
| Dose delays | Number of patients needing a dose delay in accordance with national Danish treatment guidelines(reasons for discontinuation will be registered). | through study completion, an average of 1 year and 6 months | 
| Not completing planned courses of chemotherapy | Number of patients not completing their planned courses of chemotherapy (reasons for discontinuation will be registered). | through study completion, an average of 1 year and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Neuropathy, CIPN, Cannabinoid, Cannabidiol, CBD, Neurotoxic Chemotherapy, paclitaxel, oxaliplatin