Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Anticonvulsants

Neuroprotective Agents

All Drugs and Chemicals

Riluzole

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

Protective Agents

riluzole

protein expression analysis

reverse transcriptase-polymerase chain reaction

western blotting

immunohistochemistry staining method

laboratory biomarker analysis

pharmacological study

neoadjuvant therapy

therapeutic conventional surgery

James S. Goydos, MD

RATIONALE: Riluzole may stop or slow the growth of tumor cells and may be an effective treatment for melanoma.

PURPOSE: This early phase I trial is studying how well riluzole works in treating patients with stage III or stage IV melanoma that can be removed by surgery.

OBJECTIVES:

Primary

* To evaluate the potential effects of glutamate receptor blockade on cellular pathways important in the genesis and progression of melanoma in patients with stage III or IV melanoma undergoing surgical resection.
* To determine whether treatment with riluzole alters expression of activated PLC and ERK in lysates from tumor tissue biopsies.

Secondary

* Determine if treatment with riluzole affects the overall metabolic activity of melanoma tumors as measured by pre- and post-treatment PET scanning, pre- and post-treatment tumor mitotic rate evaluation, and pre- and post-treatment immunohistochemical staining for Ki-67.

OUTLINE: Patients receive oral riluzole twice daily for 14 days. Within 24 hours after the final dose of riluzole, patients undergo standard surgical resection.

Patients undergo tumor tissue sample collection at baseline and during surgery for laboratory studies. Samples are analyzed by routine histology, immunohistochemistry, western blotting, and RT-PCR for Grm1 expression, - RAS and B-raf mutations, PLC and MAP kinase activity, Ki-67 staining, and mitotic rate. Patients also undergo blood sample collection periodically for pharmacokinetics studies.

PET scans are obtained before and after treatment to evaluate the overall metabolic activity of the tumor and how this activity changes with inhibition of the Grm1 pathway.

Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery

A Phase 0 Trial of Riluzole in Patients With Resectable Stage III and IV Melanoma

National Cancer Institute (NCI)

University of Medicine and Dentistry of New Jersey

James Goydos, MD

Symptoms and General Pathology

Recurrence

RATIONALE: Riluzole may stop or slow the growth of tumor cells and may be an effective treatment for melanoma.

PURPOSE: This phase II trial is studying how well riluzole works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery.

OBJECTIVES:

Primary

* Determine whether administration of a daily dose of riluzole results in tumor shrinkage, as measured by RECIST criteria, in patients with advanced melanoma.

Secondary

* Determine the long-term toxicity of riluzole when administered to these patients.
* Compare the survival of these patients with historical controls.

OUTLINE: Patients receive oral riluzole twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

A Phase II Trial of Riluzole in Patients With Advanced Melanoma

Per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) for target lesions and assessed by CT or MRI imaging: Complete response (CR) - disappearance of all target lesions; Partial response (PR) - \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) - At least a 20% increase in the sum of the longest diameter of target lesions; or Stable Disease (SD) - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Adverse events (AEs) were evaluated and graded using the National Cancer Institute Common Toxicity Criteria, version 3.0.

Kaplan-Meier plots of probability of overall survival.

Rutgers, The State University of New Jersey

100 mg orally twice daily

riluzole: 100 mg orally twice daily

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

No objective responses were seen in the first phase and accrual was stopped.

Tumor Response as Measured by RECIST Criteria

Number of Participants With at Least One Adverse Event

Overall Survival

Overall Study

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

The first dose of Riluzole will be day 0 of study enrollment. WBRT must begin within 48 hours of the initiation of Riluzole therapy. At the completion of radiation, Riluzole should be discontinued and steroids should be tapered over the course of 1-3 weeks, at the discretion of the treating physicians.

Standard whole brain irradiation will be carried out at 250 cGy per day fractions times 15 to a total dose of 3750 cGy using a standard opposed lateral helmet field with the inferior border inclusive of C1.

whole-brain radiation therapy

Bruce G. Haffty, MD

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs, such as riluzole, may make tumor cells more sensitive to radiation therapy. Giving riluzole together with whole-brain radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of riluzole when given together with whole-brain radiation therapy in treating patients with brain metastases.

OBJECTIVES:

Primary

* To determine the maximum tolerated dose of riluzole that can be administered concurrently with standard whole-brain radiotherapy (WBRT) in patients with multiple brain metastases.

Secondary

* To determine the long-term toxicity of riluzole when administered with WBRT.
* To assess neurocognitive function before and after treatment with riluzole and WBRT.
* To determine the MRI response of brain metastasis after treatment with riluzole and WBRT.
* To compare survival of patients treated with riluzole and WBRT to published historical data for patients with brain metastases.
* To evaluate the response of brain metastasis to riluzole and WBRT as a function of the expression of glutamate receptors on the primary tumor specimen.

OUTLINE: This is a dose-escalation study of riluzole.

Patients receive oral riluzole twice daily beginning on day 0. Beginning within 2 days after the initiation of riluzole, patients undergo whole-brain radiotherapy for 15 fractions.

Patients undergo neurocognitive and quality-of-life assessments at baseline, at 5 weeks, and at 3 months.

Tumor tissue samples are collected for laboratory biomarker studies.

After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

A Phase I Trial of Riluzole in Combination With Radiation Therapy in Patients Undergoing Whole Brain Radiation Therapy for Brain Metastasis

Peripheral Nervous System Diseases

Neuromuscular Diseases

Antineoplastic Agents

Oxaliplatin

The patient will be taken one tablet twice a day, in the morning and in the evening during the meal (12h interval). The medication is taken during the 14 days of each chemotherapy cycle, beginning 7 days before the start of chemotherapy and ending 2 weeks after the start of last cycle of chemotherapy (25 weeks). The treatment ends with the cessation of chemotherapy (visit V3 or anticipated stop).

Posology, administration and duration of treatment will be equivalent to riluzole group.

Riluzole during chemotherapy (oxaliplatin)

Placebo Oral Tablet

It is a phase II trial, randomized, parallel, double blind, multicenter, comparing riluzole versus placebo.

The trial population is composed of patients ≥18 years old that have developed stage II/III colorectal cancer and are eligible for Simplified FOLFOX4 (6-12 cycles) adjuvant chemotherapy.

The primary objective is to assess the preventive efficacy of riluzole on the severity of oxaliplatin-induced peripheral neuropathy during the Simplified FOLFOX4 adjuvant chemotherapy of stage II/III colorectal cancers.

Riluzole arm: The patient will be taken one tablet (riluzole 50 mg, film-coated tablet) twice a day, in the morning and in the evening during the meal (12h interval). The medication is taken during the 14 days of each chemotherapy cycle, beginning 7 days before the start of chemotherapy and ending 2 weeks after the start of last cycle of chemotherapy (25 weeks). The treatment ends with the cessation of chemotherapy (visit V3 or anticipated stop).

Placebo arm: The patient will be taken on tablet (placebo :50 mg, film-coated tablet) Posology, administration and duration of treatment will be equivalent to riluzole group.

Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy.

Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy: A Phase II Randomized Study by UNICANCER With the Cooperation of AFSOS

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

QLQ-CIPN20 Questionnaire (EORTC):

Self-reported questionnaire consisting of 20 questions that assess the symptoms and functional limitations of chemotherapy-induced peripheral neuropathy. The questionnaire is divided in 3 subscales: sensory, motor, and autonomic and gives a comprehensive picture of the nature, frequency, and severity of chemotherapy-induced peripheral neuropathy (CIPN). Using a 4-point Likert scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much"), patients indicate the degree to which they have experienced sensory, motor, and autonomic symptoms.

Self-reported questionnaire consisting of 20 questions that assess the symptoms and functional limitations of chemotherapy-induced peripheral neuropathy. The questionnaire is divided in 3 subscales: sensory, motor, and autonomic and gives a comprehensive picture of the nature, frequency, and severity of CIPN. Using a 4-point Likert scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much"), patients indicate the degree to which they have experienced sensory, motor, and autonomic symptoms.

The NCI-CTCAE v5.0 is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale will assess the severity of sensory neuropathic disorders, this derivative into 5 grades determined by the investigator.

This self-report questionnaire includes:

* A body schema
* The maximum pain, lowest pain, usual pain within the last 15 days (Numerical Numeric rating scales (NRS) 0 to 10
* Description of current analgesic treatment,
* An assessment of relief by a percentage scale (0-100%), Assessment of the impact of pain on: mood, relationships with others, walking, sleep, work, happiness the joy - of living, recreation, activities in general (digital scales, rating from 0 \[normal\] to 10 \[no activity\]).

The interview portion of the DN4 questionnaire is a clinician-administered screening tool for neuropathic pain. The questionnaire includes 7 items, grouped into two questions. Each item, is answered as either YES or NO. A final cumulative patient's score is obtained by allocating 1 point for each YES and 0 point for each NO. If the patient's score is ≥3/7, the test is positive.

This self-reported questionnaire assesses different neuropathic pain symptoms. The French NPSI includes 12 items that discriminates and quantifies five distinct dimensions of neuropathic pain. Each of these items are quantified on a (0-10) numerical scale.

This self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Disease Free Survival, defined as the interval between the date of randomization and the date of cancer relapse (local, regional, metastases, second cancer) or death from any cause, whichever occurs first.

The interval between randomization and deterioration ≥5 points in the HRQoL score as compared to baseline score or death (all causes).

The number of chemotherapy dose reduction caused by severe neuropathy and/or poor tolerance of treatment will be recorded.

The cumulative dose (mg/m²) of chemotherapy delivered to patients will be recorded.

The study exit rate caused by severe neuropathy and/or poor tolerance of treatment will be recorded.

Correlation with colorectal cancer tumors/nodes/metastases (TNM) score (and eventually neuropathic symptoms), glutamate plasmatic

UNICANCER

Immune System Diseases

Sclerosis

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Atrophy

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Neoplastic Processes

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Channel Blockers

Natriuretic Agents

Psychotropic Drugs

Amiloride

Fluoxetine

Selective Serotonin Reuptake Inhibitors

Serotonin

Antidepressive Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Diuretics

Sodium Channel Blockers

Diuretics, Potassium Sparing

Amiloride 5 mg twice per day (5 mg once per day for first 4 weeks) for 96 weeks

Riluzole 50 mg twice per day (50 mg once per day for first 4 weeks) for 96 weeks

Fluoxetine 20 mg twice per day (20 mg once per day for first 4 weeks) for 96 weeks

Matched placebo 1 capsule twice per day (1 capsule a day for first 4 weeks) for 96 weeks

Placebo

Jeremy Chataway

Siddharthan Chandran

Multiple sclerosis (MS) is a disabling and progressive neurological disease that affects approximately 100,000 people in the UK. Many patients with MS experience two phases of disease; early MS (also called relapsing remitting MS, RRMS) and late MS (also called secondary progressive MS (SPMS). Early MS is due to inflammation of the nerves and the insulation (called myelin) that surrounds the nerves. Early MS is often characterised by periods of "attacks" interspersed with periods of "remission" with no or low disease symptoms. Late or progressive MS, which affects the majority of patients and typically emerges after 10-15 years of disease, results from actual nerve death (also called neurodegeneration). The progressive stage of disease results not in individual attacks but slow, cumulative and irreversible disability affecting walking, balance, vision, cognition, pain control, bladder and bowel function. Critically, and unlike early disease, there is no proven treatment for the late stage of MS. This is therefore an urgent and major unmet health need. MS-SMART directly addresses this need and will evaluate in this clinical trial three drugs (fluoxetine, riluzole or amiloride), all of which have shown some promise in MS, and in particular in SPMS. The trial is randomised and blinded. Randomisation means patients can get any one of the three active drugs or the inactive placebo/dummy; blinded means that neither patients nor the doctors will know which drug or placebo patients are receiving. Randomisation and blinding are standard approaches in clinical trials to ensure unbiased testing of drugs. All patients in MS-SMART will have periodic MRI (magnetic resonance imaging) brain scans and after 96 weeks these will be analysed. We will then compare the scans of each drug to the placebo or dummy to see if any of the drugs slow the rate of brain shrinkage that normally occurs in SPMS. This measured change in brain size is the primary (major) outcome of MS-SMART.

MS-SMART will test the efficacy and mechanism of action of three repurposed drugs (fluoxetine, riluzole and amiloride). All three drugs are in human use and have a good safety record. Critically for the purpose of MS-SMART they all have shown promise in early phase human MS clinical trials and target one or more of the pivotal neurodegenerative causing pathways implicated in SPMS. This is a Type B trial, as the IMPs are all in human use, have a good safety profile but are not currently used for this patient population.

The major need for patients with established and progressive MS is neuroprotective or disease modifying treatments that will slow or even stop disease progression. This study will evaluate three highly promising putative neuroprotective drugs as well as comprehensively address several of the current knowledge gaps related to the understanding of neuroprotection and neurodegeneration in SPMS through MRI and CSF examination.

MS-SMART is a multicentre, multi-arm, double blind, placebo-controlled phase IIb randomised controlled trial. A total of 440 patients with SPMS, with an entry criteria of an EDSS score of 4.0-6.5 will be equally randomised to receive placebo or one of the three active agents (fluoxetine 20mg bd, amiloride 5mg bd or riluzole 50mg bd). Patients will be followed up for 96 weeks with outcome-data collected after 0, 24, 48 and 96 weeks. That is, the duration of the trial for a trial participant is 96 weeks (a telephone assessment at week 100, 4 weeks post completion will be conducted). This is standard practice for phase II trials in SPMS.

MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial

A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.

Persistent new T1 hypointense lesion count to assess neuroprotection in new lesions.

Grey matter volume change to assess cortical neuroprotection.

MR spectroscopy (MRS) to measure N-acetyl aspartate (reversal of neuronal mitochondrial dysfunction), myoinositol (prevention of glial cell inflammation) and glutamate (prevention of excitotoxicity).

Magnetic Transfer Ratio (MTR) to evaluate myelination.

Cervical cord imaging to assess cord neuroprotection.

Composite MRI/disability scores to increase sensitivity and study interaction of treatment mechanisms.

Quantification of Cerebrospinal fluid (CSF) neurofilament levels to measure neuroprotection.

Optical Coherence Tomography (OCT) measured Retinal Nerve Fibre Layer (RNFL) thickness as a measure of neuroprotection.

To establish whether a drug, from a panel of 3 leading candidate neuroprotective drugs, slows the rate of brain volume loss in SPMS over 96 weeks using MRI-derived percentage brain volume change (PBVC).

To establish that a multi-arm trial strategy is an efficient way of screening drugs in SPMS and can become the template for future work.

To explore any anti-inflammatory drug activity using the count of new and enlarging T2 lesions.

Examining for evidence of pseudo-atrophy (to ensure reliability of the primary outcome measure).

To examine the clinical effect of neuroprotection as measured by clinician - EDSS, MSFC, SDMT, SLCVA, relapse rate and patient reported outcome measures - MSIS29 v2, MSWS v2, Pain - NPRS and BPI and Fatigue - NFI.

To collect basic health economic data (EQ-5D) to inform future phase III trials.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery	NCT00667901	Melanoma (Skin)	riluzole protein express... reverse transcr... western blottin... immunohistochem... laboratory biom... pharmacological... neoadjuvant the... therapeutic con...	18 Years -	Rutgers, The State University of New Jersey
Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery	NCT00667901	Melanoma (Skin)	riluzole protein express... reverse transcr... western blottin... immunohistochem... laboratory biom... pharmacological... neoadjuvant the... therapeutic con...	18 Years -	Rutgers, The State University of New Jersey
Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery	NCT00866840	Melanoma (Skin)	riluzole	18 Years - 120 Years	Rutgers, The State University of New Jersey
Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases	NCT01018836	Metastatic Canc... Unspecified Adu...	riluzole whole-brain rad...	18 Years -	Rutgers, The State University of New Jersey
Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery	NCT00667901	Melanoma (Skin)	riluzole protein express... reverse transcr... western blottin... immunohistochem... laboratory biom... pharmacological... neoadjuvant the... therapeutic con...	18 Years -	Rutgers, The State University of New Jersey
Effectiveness Assessment of Riluzole in the Prevention of Oxaliplatin-induced Peripheral Neuropathy.	NCT03722680	Oxaliplatin-ind...	Riluzole Placebo Oral Ta...	18 Years -	UNICANCER
Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery	NCT00866840	Melanoma (Skin)	riluzole	18 Years - 120 Years	Rutgers, The State University of New Jersey
MS-SMART: Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial	NCT01910259	Secondary Progr...	Amiloride Riluzole Fluoxetine Placebo	25 Years - 65 Years	University College, London
Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases	NCT01018836	Metastatic Canc... Unspecified Adu...	riluzole whole-brain rad...	18 Years -	Rutgers, The State University of New Jersey

Spots Global Cancer Trial Database for riluzole

Every month we try and update this database with for riluzole 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 riluzole

Every month we try and update this database with for riluzole 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 riluzole 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.