Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

DM-CHOC-PEN is an intervention and will be dosed @ 39 mg/M2,escalated in 1-patient cohorts at 40% dosage.

* At the 1st DLT - expand to 3-6 patient cohorts/dose with escalations at 33% increments.
* The MTD will be where 2 DLTs are noted and the study is discontinued.

DM-CHOC-PEN will be dosed @ 39 mg/M2, escalated in 1-patient cohorts at 40% dosage.

At the 1st DLT - expand to 3-6 patient cohorts/dose with escalations at 33% increments.

The MTD will be where 2 DLTs are noted and the study is discontinued.

DM-CHOC-PEN

Marcus L Ware, MD

DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate that has demonstrated antineoplastic activities in human xenograft intracerebrally implanted tumor mouse models, acceptable preclinical toxicities in mouse, rat and dog models; and no behavioral cognitive impairment/neurotoxicities were noted in mouse and rat models.

The drug is ready for human use as an soy bean oil/lecithin/glycerin water emulsion, the latter which has been documented - chemically and biologically to be stable and safe. Patients are currently being enrolled and treated with the protocol.

Patients with advanced cancer, with or without central nervous system involvement will be eligible for enrollment, providing the required blood and other eligibility requirements are met.

4-Demethylcholesterylpenclomedine(DM-CHOC-PEN)is a polychlorinated pyridine cholesteryl carbonate that has demonstrated complete remissions when administrated to mice bearing intracranially implanted human cancer xenografts (glioblastomas and breast cancers) and has acceptable preclinical toxicity profiles - mice, rats and dogs.

The drug is being administered intravenously once every 21 days as an infusion. The starting dose was 39 mg/M2 (based on 1/10 LD10 observed in mice and rats).

A modified accelerated dosing protocol of Simon, Freidlin, et al is in process to escalate dosage which will reduce the number of patients required and minimize ineffective doses. The protocol will result in one patient cohorts at 40% dosage escalations. When the 1st instance of a dose limiting toxicity (DLT) \[grade - 3 or 4 toxicity\] is observed, or the 2nd instance of a 1st course grade 2 toxicity of any type is observed, the cohort for that current dose level will be expanded to 3-6 patients and escalation will proceed at 33% increments.

During the entirety of the study, intra-patient escalation will be allowed. This will occur if the patient experiences are \< grade 2 toxicity at the existing dose, if no \> grade 2 toxicity was identified at the existing dose and no DLTs were noted at the higher dose level (if any patients had been escalated to that dose).

Continuation of therapy - Patients who experience stabilization, partial or complete remission while being treated will continue to receive the drug as per the last dose prior to identifying positive results at an every 3 weeks interval.

Discontinuation of therapy - progressive disease and/or toxicities.

Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer

A Protocol for the Safety and Tolerance of Intravenous 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer

National Cancer Institute (NCI)

DEKK-TEC, Inc.

Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer"

Patients were treated in cohorts from 39-111 mg/m2 single IV doses. Hepatic toxicity was a limiting factor for patients w/ liver disease.

Phase II trials will be 2-tier - w/ liver involvement and without,.

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Temozolomide (Schering-Plough) 200 mg/m2, single oral dose.

Temozolomide (Monte Verde S.A.) 200 mg/m2, single oral dose

Alejandro D Muggeri, Physician

The purpose of this crossover, single-dose, bioequivalence study is to compare the rate and extent of absorption of Temozolomide after the administration of the study product (Dralitem®, Monte Verde S.A.) and the reference product (Temodal®, Schering Plough) in primary Central Nervous System patients.

Prospective, randomized, two-period, two treatment, two-way crossover bioequivalence study of two Temozolomide oral formulations (Dralitem vs. Temodal), in primary Central Nervous System tumor patients under fasting conditions. Open label to the patients and investigators and blind to the bioanalytical and clinical laboratories.

Study plan: days -21 to 0 (Recruitment period); days 1 to 5 (Treatment period); days 6 to 21 (Safety surveillance period). Sample size: 24 patients will be randomized. The patients will be administered Temozolomide 200 mg/m2 on the first two days (Dralitem) of the treatment cycle.

They will be admitted to the study clinical site on the evening of day 2. In the morning of day 3 they will be randomized into two groups of equal size. According to the assigned random number, each subject will receive a single oral dose of Temozolomide 200mg/m2 from either Monte Verde Sociedad Anónima (SA) product (Dralitem) or from Schering-Plough product (Temodal). The single dose of 200 mg/m2 will be reached with three different Temozolomide capsule strengths: 20, 100 and 250 mg. Drugs will be administered with 200-240 ml of water in semi-sitting upright position.

The following day (day 4) each subject will receive an oral dose of Temozolomide 200 mg/m2 of the product that did not receive the day before. On days 3 and 4 after drug administration, blood samples will be obtained for pharmacokinetic evaluation. The patient will be discharged from the clinical site on day 4 after completion of sampling for pharmacokinetic analysis. On day 5, all patients will receive Temozolomide 200 mg/m2 (Dralitem).

On days 3 and 4, samples of venous blood will be withdrawn from the forearm vein of each volunteer at the following time points: 0 (pre-dose) and 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 hours post-dose after each period administration. The washout period between the treatment arms was 10 hours, on days 3 and 4. Samples will be processed according to the validated method MANA (Método Analítico) - PLB (Proyecto Laboratorio Bioanalítico) 004 - TEM (Temozolomide) - 01/01. Measurement of plasma concentration of Temozolomide was performed using High Performance Liquid Chromatography (HPLC) followed by detection by tandem mass spectrometry (MS / MS).

The area under the curve (AUC) and the Cmax levels of the drug vs. time will be obtained for each subject. The resulting values of the logarithmic transformation of these parameters will be used for statistical comparisons (mixed effects ANOVA). The limits of the 90% confidence interval for the ratio of log transformed pharmacokinetic parameters will be calculated. Bioequivalence criteria: each calculated confidence interval should be within the acceptance range from 80.00 to 125.00.

Bioequivalence Study of Temozolomide in Patients With Primary Tumors of the Central Nervous System

A Randomized, Open Label, Two-way Crossover, Single Dose Bioequivalence Study Comparing Dralitem® Capsules to the Reference Drug Temodal® Capsules in Patients With Primary Tumors of the Central Nervous System Under Fasting Conditions

Rate at which Temozolomide is removed from the body.

Time required for Temozolomide plasma concentration to decrease by 50%

Rate of absorption of Temozolomide (Cmax) will be measured after the oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough).

Extent of absorption of Temozolomide from time (0) to the last quantifiable concentration (t) will be measured after the oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough)

Extent of absorption of Temozolomide from time (0) to infinity (∞) will be measured after oral administration of the test product (Dralitem®, Monte Verde S.A.) or the reference product (Temodal®, Schering-Plough).

AEs and SAEs will be collected from the start of study treatment and until two weeks post last dose. If AEs or SAEs extend in time and are not resolved before the end of the 2-week follow up period, this period shall last until the event/s are resolved.

FLENI Instituto de Rehabilitación y Educación Terapéutica, BA, Argentina.

Bioanalytical Unit, Laboratorio Raffo S.A., BA, Argentina.

FLENI Multi-Specialty Research Center, BA, Argentina.

Monte Verde SA

Safety population included all subjects who received at least one dose of intervention.

Temodal

Temozolomide (Monte Verde S.A.) 200 mg/m2, single oral dose.

Dralitem

During days 1 and 2, all patients received a single oral dose of 200 mg/m2 of Temozolomide from Monte Verde S.A. (Dralitem®). On day 3 patients received 200 mg/m2 of Temozolomide from Schering-Plough (Temodal®) as a single oral dose. After a washout period of 10 hours, they then received 200 mg/m2 of Temozolomide from Monte Verde S.A. (Dralitem®). On day 5 all patients received Temozolomide 200 mg/m2 from Monte Verde S.A. (Dralitem®).All patients were under fasting conditions two hours before and after each drug administration.

Temodal, Then Dralitem

During days 1 and 2, all patients received a single oral dose of 200 mg/m2 of Temozolomide from Monte Verde S.A. (Dralitem®). On day 3 patients received 200 mg/m2 of Temozolomide from Monte Verde S.A. (Dralitem®) as a single oral dose. After a washout period of 10 hours, they then received 200 mg/m2 of Temozolomide from Schering-Plough (Temodal®). On day 5 all patients received Temozolomide 200 mg/m2 from Monte Verde S.A.(Dralitem®). All patients were under fasting conditions two hours before and after each drug administration.

Dralitem, Then Temodal

Total

Age, Continuous

Sex: Female, Male

Argentina

Region of Enrollment

Height

Weight, Continuous

Body Surface, Continuous

Body Mass Index

Dr. Alejandro Muggeri (Principal Investigator)

Bioequivalence assessment was made for the 90% CI for the ratio of log transformed pharmacokinetic parameters μT / μR and with the two one-sided Schuirmann T-test procedure under the null hypothesis

Temozolomide (Schering-Plough) 200 mg/m2, single oral dose.

Temozolomide

Temozolomide (Monte Verde S.A.) 200 mg/m2, single oral dose

Temozolomide

All those subjects who completed the study and were compliant with all the protocol procedures were considered evaluable for statistical pharmacokinetic analysis. Those who received at least one dose of the products under study but did not comply with the study procedures were included in the safety analysis only.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer	NCT01048008	Advanced Cancer Brain Involveme...	DM-CHOC-PEN	18 Years -	DEKK-TEC, Inc.
Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer"	NCT01976910	Advanced Cancer	DM-CHOC-PEN	18 Years -	DEKK-TEC, Inc.
Bioequivalence Study of Temozolomide in Patients With Primary Tumors of the Central Nervous System	NCT02343081	Brain Neoplasms...	Temozolomide Temozolomide	21 Years -	Monte Verde SA
Bioequivalence Study of Temozolomide in Patients With Primary Tumors of the Central Nervous System	NCT02343081	Brain Neoplasms...	Temozolomide Temozolomide	21 Years -	Monte Verde SA
Study of 4-Demethylcholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) in Patients With Advanced Cancer	NCT01048008	Advanced Cancer Brain Involveme...	DM-CHOC-PEN	18 Years -	DEKK-TEC, Inc.
Bioequivalence Study of Temozolomide in Patients With Primary Tumors of the Central Nervous System	NCT02343081	Brain Neoplasms...	Temozolomide Temozolomide	21 Years -	Monte Verde SA

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