Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Anticoagulants

Herbal and Botanical

Other Dietary Supplements

Mebendazole

Piperazine

Piperazine citrate

DMP 777

Citric Acid

Sodium Citrate

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Anthelmintics

Antiparasitic Agents

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Cola

Citrate

Folfox with avastin

Sherief Abd-Elsalam, ass. prof.

Sherief Abd-elsalam, lecturer

Reham El-ghoneimy, Msc

Sahar Hegazy, Prof

Gamal el-azab, Prof

Fatma Zakaria, Prof

mebendazole as adjuvant treatment for colon cancer

Mebendazole as Adjuvant Treatment for Colon Cancer

Clinical Study Evaluating Mebendazole as Adjuvant Therapy in Patients With Colorectal Cancer

Sherief Abd-Elsalam

Ass. Prof. Tropical Medicine

Nervous System Diseases

Eye Diseases

Rare Diseases

Glioblastoma

Glioma

Diffuse Intrinsic Pontine Glioma

Astrocytoma

Gliosarcoma

Optic Nerve Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Optic Nerve Neoplasms

Peripheral Nervous System Neoplasms

Cranial Nerve Diseases

Optic Nerve Diseases

Anaplastic Astrocytoma

Pilocytic Astrocytoma

Pleomorphic Xanthoastrocytoma

Neuroepithelioma

Anticonvulsants

Carboplatin

Irinotecan

Temozolomide

Vincristine

Topoisomerase I Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients on the low-grade arm will receive treatment with seven 10-week cycles of carboplatin, vincristine, temozolomide, and mebendazole.

Patients on the high-grade glioma/pontine glioma arm will receive treatment with twelve 28-day cycles of bevacizumab, irinotecan, and mebendazole.

\*High grade arm enrollment complete, no additional spots

Mebendazole will be given orally twice daily for over the course of treatment (70 weeks for low-grade glioma patients, 48 weeks for high-grade glioma/pontine glioma patients). Mebendazole will be prescribed according to the particular dose cohort for each patient (50 mg/kg/day, 100 mg/kg/day, or 200 mg/kg/day).

Low-grade glioma patients only. Vincristine will be dosed as per the following: For patients \< 12kg: 0.05 mg/kg; for patient \> 12kg: 1.5mg/m2 (maximal dose 2.0 mg). Vincristine will be administered intravenously on Day 1 of weeks 0,1,2,3,4,5 during the 10-week induction cycle and on Day 1 of Weeks 0,1,2 of the six 10-week maintenance cycles.

Low-grade glioma patients only. Carboplatin will be dosed at 175 mg/m2. Carboplatin will be administered intravenously on Day 1 of Weeks 0,1,2,3 of the 10-week Induction cycle, and on Day 1 of Weeks 0,1,2,3 during the six 10-week maintenance cycles.

Low-grade glioma patients only. Temozolomide will be dosed at 200 mg/m2/day. Temozolomide will be given orally for 5 days during Week 6 of the 10-week induction cycle and for 5 days during Week 6 of the six 10-week maintenance cycles.

High-grade glioma/pontine glioma patients only. Bevacizumab will be dosed at 10mg/kg/dose. Bevacizumab will be administered intravenously on Days 1 and 15 of each maintenance cycle.

High-grade glioma/pontine glioma patients only. Irinotecan will be administered at doses 125 mg/m2, 150 mg/m2, 250 mg/m2, or 300 mg/m2, depending on patient tolerance and concomitant enzyme-inducing anti-epileptic medication use. Irinotecan will be administered intravenously on Days 1 and 15 of each maintenance cycle.

Julie Krystal, MD

Derek R Hanson, MD

Mark P Atlas, MD

This is a study to determine the safety and efficacy of the drug, mebendazole, when used in combination with standard chemotherapy drugs for the treatment of pediatric brain tumors. Mebendazole is a drug used to treat infections with intestinal parasites and has a long track record of safety in humans. Recently, it was discovered that mebendazole may be effective in treating cancer as well, in particular brain tumors. Studies using both cell cultures and mouse models demonstrated that mebendazole was effective in decreasing the growth of brain tumor cells.

This study focuses on the treatment of a category of brain tumors called gliomas. Low-grade gliomas are tumors arising from the glial cells of the central nervous system and are characterized by slower, less aggressive growth than that of high-grade gliomas. Some low-grade gliomas have a more aggressive biology and an increased likelihood of resistance or recurrence.

Low-grade gliomas are often able to be treated by observation alone if they receive a total surgical resection. However, tumors which are only partially resected and continue to grow or cause symptoms, or those which recur following total resection require additional treatment, such as chemotherapy. Due to their more aggressive nature, pilomyxoid astrocytomas, even when totally resected, will often be treated with chemotherapy. The current first-line treatment at our institution for these low-grade gliomas involves a three-drug chemotherapy regimen of vincristine, carboplatin, and temozolomide. However, based on our data from our own historical controls, over 50% of patients with pilomyxoid astrocytomas will continue to have disease progression while on this treatment. We believe that mebendazole in combination with vincristine, carboplatin, and temozolomide may provide an additional therapeutic benefit with increased progression-free and overall survival for low-grade glioma patients, particularly for those with pilomyxoid astrocytomas.

High grade gliomas are more aggressive tumors with poor prognoses. The standard therapy is radiation therapy. A variety of adjuvant chemotherapeutic combinations have been used, but with disappointing results. For high-grade gliomas this study will add mebendazole to the established combination of bevacizumab and irinotecan to determine this combinations safety and efficacy

This is a phase I/II study of mebendazole in combination with standard of care agents for pediatric patients with gliomas. Patients with low-grade gliomas will receive a regimen of mebendazole in combination with vincristine, carboplatin, and temozolomide. Patients with high-grade gliomas and diffuse intrinsic pontine gliomas will receive a regimen of mebendazole in combination with bevacizumab and irinotecan. Surgical resection of the tumor will be attempted initially with the goal of achieving a gross total resection without substantial neurologic deficit. Subtotal resection may be preferable depending on the location of the tumor. Optic pathway gliomas and diffuse intrinsic pontine gliomas may remain unresected. Patients with high-grade gliomas or diffuse intrinsic pontine gliomas will undergo local irradiation of their tumor before beginning protocol treatment. Low-grade glioma patients will not receive radiation therapy. Patients who have been previously treated with chemotherapy will be eligible for the study provided they have not previously failed therapy with any of the chemotherapeutic agents.

Patients with eligible tumors will be consented for enrollment into the study. The study patients will be divided into two groups (low-grade glioma and high-grade/pontine glioma) for the purpose of determining the maximally tolerated dose of mebendazole. These two groups will be treated independently with regard to patient accrual, dose escalation, and evaluation of toxicity. In addition to their standard chemotherapy regimen, patients in both cohorts will receive mebendazole. Mebendazole doses will be escalated from the initial dose level of 50 mg/kg/day divided twice daily, to a second dose level of 100 mg/kg/day divided twice daily, to the final dose level of 200 mg/kg/day divided twice daily, in cohorts of three patients per dose level. A standard "3+3" design will be used for determining dose escalation.

Phase I safety monitoring for the low-grade group will take place during a trial period beginning with start of therapy and ending following the tenth week of induction therapy. Phase I safety monitoring for the high-grade/pontine glioma group will take place during a trial period beginning with the start of maintenance therapy through the twelfth week of maintenance therapy (3 cycles).

After determination of maximally tolerated dose for each group, the study will continue to evaluate efficacy of this regimen. The study will be amended for the maximally tolerated dose for each group to be used in the remainder of the study. Patients currently on study will continue with maintenance therapy. To document the degree of residual tumor, standard whole brain MRI with and without contrast (gadolinium) will be performed following a specified intervals. Following completion of therapy, patients will continue to be monitored by MRI to assess progression-free and overall-survival.

A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

Low-grade glioma patients will receive an assigned dose of mebendazole twice daily in combination with vincristine, carboplatin and temozolomide. During a 10 week induction period, patients will be assessed for dose-limiting toxicity that is beyond the expected toxicity from the standard regimen of vincristine, carboplatin, and temozolomide alone. This outcome measure will use a standard 3+3 design to dose-escalate mebendazole in three dose cohorts of 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day.

High-grade glioma/pontine glioma patients will receive an assigned dose of mebendazole twice daily in combination with bevacizumab and irinotecan. During the first three maintenance therapy cycles (12 weeks), patients will be assessed for dose-limiting toxicity that is beyond the expected toxicity from the standard regimen of bevacizumab and irinotecan alone. This outcome measure will use a standard 3+3 design to dose-escalate mebendazole in three dose cohorts of 50 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day.

3-year event-free survival (EFS) and overall survival (OS) of patients with low-grade gliomas treated with carboplatin, vincristine, temozolomide, and mebendazole in combination following surgical resection, to the extent feasible.

3-year event-free survival (EFS) and overall survival (OS) of patients with high-grade gliomas treated with bevacizumab, irinotecan, and mebendazole in combination following surgical resection to the extent feasible and local irradiation.

The frequency of tumor dissemination in the CSF of patients with pilomyxoid astrocytomas treated with carboplatin, vincristine, temozolomide, and mebendazole.

The percentage of patients demonstrating a partial (greater than 50% decrease in tumor volume in 3 dimensions) or complete response on MRI in patients with high-grade gliomas treated with mebendazole in combination with bevacizumab and irinotecan, after surgical resection, to the extent feasible and local irradiation.

The percentage of patients demonstrating a partial (greater than 50% decrease in tumor volume in 3 dimensions) or complete response on MRI in patients with low-grade gliomas treated with mebendazole in combination with vincristine, carboplatin and temozolomide after surgical resection, to the extent feasible.

Janssen Pharmaceuticals

Julie Krystal

Head, Developmental Therapeutics

Symptoms and General Pathology

Carcinoma

Liver Cirrhosis

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Liver Diseases

Fibrosis

Lenvatinib

Protein Kinase Inhibitors

Lenvatinib will be given once a day(OD) orally at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg ) with placebo (Tab Mecovit) orally twice a day (BD) daily

Lenvatinib will be given orally once a day (OD) at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg) and mebendazole will be given at dose of 100 mg orally twice a day (BD) daily

Lenvatinib will be given once a day(OD) orally at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg

mebendazole will be given at dose of 100 mg orally twice a day (BD) daily

Placebo (Tab Mecovit) orally twice a day (BD) daily

Placebo

Dr Navin Kumar, MD

Dr Naveen Kumar, MD

Currently the available first line palliative therapy for advanced HCC is Sorafenib and Lenvatinib of which Lenvatinib is tolerated better. Unfortunately, patients tend to progress after few months of therapy. Therefore it is imperative, to do trials by combinative therapy to the available therapy for added survival benefits and quality of life with advanced HCC. In this regard, Mebendazole appears to be a good choice for drug repurposing as it has shown very promising results either alone or in combination with other therapies in tumors of GI origin and CNS tumors. With regard to HCC Mebendazole has been found to be effective in vitro system of HCC and preclinical models. However no clinical trials have been initiated till now. The key hallmark features of HCC include activation of MAPK and angiogenesis which in turn are targeted by RTK inhibitors such as Sorafenib and Lenvatinib. In this regard Mebendazole has broad range of action by not only inhibiting angiogenesis and pro-survival pathways of MAPK, but by also inhibiting the secretion of MMPs and Tubulin polymerization which can all be beneficial in tumor regression and prevention of chemo-resistance in HCC. Mounting of a strong immune response plays an important role in identification of tumor antigen and thereby clearing of tumors. While Mebendazole can modulate the tumor, the data is scant with respect to the role of the drug. Hence repurposing Mebendazole as a combinatorial therapy appears a promising approach and forms the basis of the present work. We hypothesize that combinatorial therapy of addition of mebendazole to lenvatinib will prove more beneficial than lenvatinib alone in increasing the overall survival of patients with advanced HCC. To prove the mechanistic effects of mebendazole on HCC, we will also conduct a animal study in preclinical mice model of HCC with the help of our animal house facility. The animal study will help us to understand the additional benefits from mebendazole and lenvatinib with objective evidence of liver biopsy which is not feasible in humans.

(A) STUDY HYPOTHESIS

* Mebendazole augments response of lenvatinib by synergistic response.
* Addition of anti angiogenic drugs (lenvatinib and mebendazole) to hypoxic environment generated post locoregional therapy like TACE leads to more effective control of advanced HCC resulting in improvement in overall survival.

(B) AIM: To compare the efficacy of combination of mebendazole with lenvatinib in cirrhotics with advanced Hepatocellular Carcinoma.

(C) OBJECTIVE:

Primary objective:

To compare the efficacy of combination of mebendazole with lenvatinib in improving the overall survival at 15 months in cirrhotics with advanced HCC.

Secondary objective:

1. To compare the progression free survival with combination therapy of mebendazole and lenvatinib in advanced Hepatocellular Carcinoma (HCC).
2. To compare the objective response rate (ORR), disease control rate (DCR) and clinical benefit rate (CBR) with combinative therapy of mebendazole and lenvatinib in advanced HCC.
3. To study therapy related adverse effects of mebendazole in cirrhotics.
4. To develop pre-clinical HCC animal model to prove the added efficacy of combination therapy.

(D)STUDY DESIGN Type of study - Single center, prospective, open label, randomized control study Study population - cirrhosis of liver of any etiology with advanced HCC undergoing at ILBS Study duration - 22 months from the date of approval of IEC Sample size - Considering mebendazole adds 2 months more to lenvatinib which offers 13 months overall survival, power of the study as 80 %, attrition rate as 30 %, alpha error of 5%, sample size will be 85 patients in each arm ( totally 170 patients).

(F) Methodology: Cirrhotics with advanced HCC proven by imaging and or biopsy or cytology, fulfilling the eligibility criteria will be enrolled in the study. They may undergo 1 or 2 sessions of locoregional therapy (TACE/ SBRT/RFA) if feasible. All patients will undergo complete physical examination, CBC, LFT, KFT, INR, AFP, PIVKAII, CEMRI/ CECT upper abdomen (Triple phase ), UGI endoscopy at baseline before randomization.

Randomization:

Those patients who are not feasible for locoregional therapy will be randomized at baseline. Those patients undergoing locoregional therapy will be randomized after 1 month of last locoregional therapy (patient may undergo maximum of two sessions of locoregional therapy before randomization). The response will be determined by m RECIST criteria before randomization. Those patients requiring further sessions of locoregional therapy beyond two sessions will not be randomized into study.

Patient will be then randomized to one of the two groups Arm I :Lenvatinib +Placebo( Lenvatinib will be given once a day(OD) orally at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg ) with placebo (Tab Mecovit) orally twice a day (BD) daily Arm II : Lenvatinib and mebendazole ( Lenvatinib will be given orally once a day (OD) at dose of 8 mg if body weight is \< 60 kg and 12 mg if body weight is \> 60 kg) and mebendazole will be given at dose of 100 mg orally twice a day (BD) daily

Follow-up Patients will be followed up with clinical events, CBC, LFT, KFT, INR, AFP, PIVKAII, CEMRI/ CECT upper abdomen (Triple phase ) at the end of 1 month, 3 months, 6 months, 9 months, 12 months and 15 months.

INVESTIGATIONS AND FOLLOW UP At Baseline (before therapy) and during follow up

* Hematology- repeated at the end of 1, 3, 6, 9, 12, 15 months.

  - CBC
* Biochemistry - repeated at the end of 1, 3, 6, 9, 12, 15 months.

  * Serum Electrolytes, Kidney function test
  * Liver function test, INR
* CTP and MELD scores
* AFP, PIVKA II - repeated at the end of 1, 3, 6, 9, 12, 15 months.
* UGIE at baseline
* CEMRI / CECT upper abdomen - Triple phase - repeated at the end of 1, 3, 6, 9, 12, 15 months.
* PET CT - if systemic spread suspected or else at the end of 6 and 15 months
* Liver Biopsy/FNAC will be done in cases where its clinically indicated.

The pre-clinical model will be developed in mice, for which separate application will be submitted to the animal ethics committee of the institute.

Timeline of follow up

* At the end of first month
* Then every 3 months until 15 months after starting therapy

STATISTICAL ANALYSIS

* Data will be reported as mean + SD
* Categorical variables will be compared using the chi-square test or Fisher exact test
* Normal continuous variables will be compared using the Student t test
* Non normal continuous variables will be compared using the Mann-Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data).
* Comparison between groups on quantitative variables will be analyzed by ANOVA
* The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test
* A Cox regression analysis will be performed to identify independent prognostic factors for survival.

Intervention: This Randomized Controlled trial will be conducted at Institute of Liver \& Biliary SciencesLBS New Delhi between June 2020 and March 2022

Salvage therapy

* TACE or TARE if progressive disease
* Nivolilumab if the patient had a progressive disease at 6 months of therapy

To Study the Effects of Addition of Mebendazole to Lenvatinib in Cirrhotics With Advanced Hepatocellular Carcinoma.

Worsening of performance will be measured by Eastern Cooperative Oncology Group (ECOG) Criteria.

Barcelona-Clinic Liver Cancer (BCLC) staging classification will be used.

Institute of Liver and Biliary Sciences, India

Recurrence

Medulloblastoma

Oligodendroglioma

Brain Tumor, Childhood

Anaplastic Oligodendroglioma

oral mebendazole as dose escalation (three groups), or l oral mebendazole at maximum dose for extended cohort. Given in 3 divided doses with meals as chewable 500 mg tablets based on calculated patient surface area.

chewable mebendazole tablets that can also be crushed and mixed with food or drink to be taken daily with meals

Kenneth J Cohen, MD

This is a safety (Phase 1) trial using mebendazole for recurrent pediatric brain cancers that include medulloblastoma and high grade glioma, that are no longing responding to standard therapies. The drug mebendazole is an oral drug in a chewable 500 mg orange flavored tablet. It is already approved to treat parasitic infections. The purpose of this study is to determine the safety and side effects for increasing doses of mebendazole, followed by the treatment of an additional 12 patients at the best tolerated dose.

The primary objectives of this study are to determine the maximum tolerated dose (MTD) of oral mebendazole in patients with recurrent/progressive pediatric brain tumors and to confirm the tolerance of the MTD of oral mebendazole by assessing tolerance in a dose expansion cohort. Secondary Objectives of the study include to determine the safety, tolerability and toxicity of mebendazole in this patient population, determine the plasma levels of mebendazole in this patient population and Determine progression-free and overall survival of mebendazole in an extended cohort of patients with treatment refractory pediatric brain cancer.

Mebendazole (MBZ) is a drug developed to treat human helminthic disease and is FDA-approved for the treatment of roundworm, common hookworm, American hookworm, pinworm and whipworm. MBZ use is well documented and frequently used in tropical countries at higher doses for the rarer parasitic infections of the brain.

We have shown efficacy in preclinical laboratory models of high grade glioma and medulloblastoma. Mebendazole therapy demonstrated safety in a phase I clinical trial for adults with high grade gliomas such as glioblastoma. This trial completed the maximum approved enrollment of 24 patients treated with mebendazole, with high doses consistent with dosing published for severe parasitic infections.

Laboratory studies indicate that mebendazole enters the brain and brain tumors at concentrations that may be effective for a combination of anti-cancer mechanisms. In animal models of brain cancer evidence suggest that mebendazole can prevent cell proliferation by interfering with tubulin formation, and it may prevent the formation of new abnormal blood vessels that feed tumor growth.

The patients for this experimental trial are those between the age of 1 to 21 with the diagnosis of medulloblastoma, or high grade glioma, where the tumor has resumed growth or continued to grow despite standard medical therapy. High grade glioma are those with a World Health Organization (WHO) grade of III or IV. It includes diagnosis of pediatric glioblastoma, anaplastic astrocytoma, and diffuse intrinsic pontine glioma. Patients who have failed other forms of experimental therapy may also be eligible for this trial.

Mebendazole is provided at no cost in the form of a chewable 500 mg tablets, recommended to be taken three times daily with meals or food. The pill can be chewed after meals, or ground up to be mixed with food or drink. It has a mild orange flavor that is similar in consistency to an antacid tablet.

Although side effects are rare and the vast majority are reversible, they include stomach upset, decreased blood count, and elevated liver enzymes due to inflammation.

The main additional procedure beyond taking this drug, is that patients are requested to consent to up to three additional blood draws to check the blood (serum) levels of the drug to ensure it is being absorbed at sufficient doses.

Patients can continue to receive the drug as long as in the attending physicians opinion the therapy is not causing any severe side effects, and there is no clear indication that the patient will not respond to mebendazole therapy. Patients can withdraw from this trial at any time for any reason, and may be eligible for other experimental therapies afterwards.

Phase I Study of Mebendazole Therapy for Recurrent/Progressive Pediatric Brain Tumors

A peer reviewed publication in a medical journal with the results from the study is planned upon completion of the study,that may/may not have data from individual participants compliant with HIPPA protection.

cumulative adverse events from mebendazole therapy in pediatric brain cancer patients

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Hypoglycemic Agents

Lipid Regulating Agents

Ibuprofen

Metformin

Doxycycline

Atorvastatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Anti-Bacterial Agents

Antimalarials

Antiprotozoal Agents

Subjects will take the following treatments and have their data collected from their medical records every 3 months.

* Oral atorvastatin up to 80mg uid, for study duration.
* Oral metformin up to 1000mg uid, increased to bid if tolerated after 2 weeks, for study duration.
* Oral doxycycline 100mg uid, for study duration.
* Oral Mebendazole 100mg uid, for study duration.

While subjects are being treated with the four metabolic drugs, every 3 months they will bring in their medical records and data will be collected to determine the effect of the intervention

Metabolic treatment

Samir Agrawal, MRCP FRCPath

The purpose of this study is to determine the effectiveness of a regimen of selected metabolic treatments for patients with cancer in a real world setting and to conduct exploratory analysis on the relationship between the degree of response and changes in biochemical markers (such as glucose and lipid levels).

\*This study has been designed to collect data prospectively and to retrospectively analyse data on the metabolic treatments within the cancer clinic. The retrospective study is ongoing, while the prospective study has not yet started.\*

This is a real world study since this gives the best opportunity to properly examine the effect of multi-drug regimens in representative populations. Including a standard of care arm is inappropriate, in a population in which that standard of care has already been shown to be ineffective or intolerable.

Patients will be sent to the study clinic directly by their Health Care Professionals ("HCP's") .

The study will consist of a pre-screening visit to determine eligibility for inclusion into the study, an initiation visit and then a follow up visit every three months thereafter. If required, unscheduled visits may take place. Day 0 (baseline) for each patient will be the initiation visit when study treatment is started.

Prior to conducting any study-related procedures, subjects will provide written informed consent, eligibility will be assessed, a medical history and past medical records will be taken and vital signs will be measured. These records will include the stage of their disease, response to previous cancer therapy, their prior and current medications and any specific regimen they are currently on for their cancer. If prior medical records do not contain sufficient information to determine a baseline for the patient, additional blood tests and scans will be undertaken as appropriate.

Patients will be monitored quarterly thereafter when blood tests (e.g. safety parameters, glucose, cholesterol, immune response and cancer markers where applicable) and scans (where applicable) will be taken.

All patients will be on the same drug regimen (see below) at the same doses throughout the study. All patients will be followed up until they choose to leave the study, or death.

Data from all patients recruited to the study will be analysed using an Intention-to-treat (ITT) philosophy, so data will be included in the primary analysis irrespective of whether the dose regimen was followed throughout the study. If appropriate, and numbers allow, analysis will also be conducted on the Per Protocol population, comprising those patients who adhere to the regimen as prescribed.

Survival analysis methods will be used to estimate the Overall survival associated with the study regimen for each type of cancer. These estimates will be interpreted in the light of data obtained from the literature, and from eliciting expert opinion. Bayesian methods may be used where appropriate.

Tumour response, where applicable, will be summarised in tables and graphs. Estimates of response rates will be presented for each cancer type with confidence intervals.

The relationship between changes in biochemistry values (glucose, lipids) and efficacy outcomes (Progression Free Survival (PFS), Overall Survival (OS) and HRQoL) will be investigated graphically, or using other methods as appropriate.

Further exploratory analysis to investigate the effects of other factors such as age , ethnic backgrounds , cancer stage, and response to prior therapy, will also be conducted in order to try and characterise the profile of patients most likely to benefit from the study regimen.

The characteristics of patients on the regimen and those who do not stay on the regimen, for whatever reason, will be summarised to see whether there is any observed bias. If appropriate, methods will be used to adjust for any observed bias, for example using propensity scores. OS can then be assessed adjusted for this to try and mitigate for any possible risk of bias which can occur in uncontrolled studies. Furthermore, by enrolling all eligible patients over a specified time frame, it is hoped that the risk of bias should be further reduced. In addition, a large number of patients are expected to participate in the study.

Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer

A Non Randomised, Non Blinded Real World Trial of the Safety, Tolerability and Effectiveness of Metabolic Medicines for the Treatment of Cancer Compared Against Matched Controls

Adverse events reported by the subject or their HCP.

• Quarterly assessment of routine laboratory tests

Overall survival for all cancer types and for each cancer type (years and months)

Tumour size for all cancer types and for each cancer type. Units of size vary depending on cancer type.

Tumour spread (metastasized) to other tissues/organs, for all cancer types and for each cancer type. This is measured as either 0 for no spread or 1 for confirmed spread.

Tumour number for all cancer types and for each cancer type

Cancer biomarkers for all cancer types and for each cancer type. Units of measurement vary depending on the cancer type. When biomarkers, either alone or in combination with other biomarkers, are raised above normal they are seen as predictive of cancer of progression. If returned to normal are indicative of treatment response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mebendazole as Adjuvant Treatment for Colon Cancer	NCT03925662	Colorectal Canc...	Folfox with ava... Mebendazole	18 Years -	Tanta University
A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas	NCT01837862	Pilomyxoid Astr... Pilocytic Astro... Glioma, Astrocy... Optic Nerve Gli... Pleomorphic Xan... Glioblastoma Mu... Anaplastic Astr... Gliosarcoma Diffuse Intrins... DIPG Low-grade Gliom... Brainstem Gliom...	Mebendazole Vincristine Carboplatin Temozolomide Bevacizumab Irinotecan	1 Year - 21 Years	Northwell Health
To Study the Effects of Addition of Mebendazole to Lenvatinib in Cirrhotics With Advanced Hepatocellular Carcinoma.	NCT04443049	Hepatocellular ... Liver Cirrhosis	Lenvatinib Mebendazole Placebo	18 Years - 70 Years	Institute of Liver and Biliary Sciences, India
Phase I Study of Mebendazole Therapy for Recurrent/Progressive Pediatric Brain Tumors	NCT02644291	Medulloblastoma Astrocytoma, Gr... Glioblastoma Anaplastic Astr... Brain Stem Neop... Oligodendroblas... Anaplastic Olig... Malignant Gliom...	Mebendazole	1 Year - 21 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer	NCT02201381	Cancer Overall Surviva...	Metabolic treat...	18 Years - 85 Years	Health Clinics Limited
To Study the Effects of Addition of Mebendazole to Lenvatinib in Cirrhotics With Advanced Hepatocellular Carcinoma.	NCT04443049	Hepatocellular ... Liver Cirrhosis	Lenvatinib Mebendazole Placebo	18 Years - 70 Years	Institute of Liver and Biliary Sciences, India
Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer	NCT02201381	Cancer Overall Surviva...	Metabolic treat...	18 Years - 85 Years	Health Clinics Limited
Study of the Safety, Tolerability and Efficacy of Metabolic Combination Treatments on Cancer	NCT02201381	Cancer Overall Surviva...	Metabolic treat...	18 Years - 85 Years	Health Clinics Limited

Spots Global Cancer Trial Database for mebendazole

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

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