A Phase 1 Continuous Intravenous Infusion Study of Terameprocol (EM-1421) in Subjects With Refractory Solid Tumors

Lymphoma Clinical Trial

Official title: A Phase 1 Continuous Intravenous Infusion Study of Terameprocol (EM-1421) in Subjects With Refractory Solid Tumors.

Status Terminated

Clinical Trial Summary

This is a Phase I continuous infusion study designed to explore if constant concentration over time adds to the effectiveness of terameprocol without increasing toxicity. It will also explore weekly dosing as an option.

Tumor response assessments will be performed following every two (2) cycles of therapy. All subjects will undergo a follow-up visit 30 days following their last dose of terameprocol. Circulating tumor cells (CTC) will be quantified pre dosing and on day 15 after first dose of each cycle. Needle biopsy specimens will be taken prior to therapy and one week after first dose, if possible, to assess for tumor markers (cdc-2 and survivin). Tumor markers, for example prostate specific antigen (PSA) will also be measured on day 15 of each cycle (if elevated on study entry). Pharmacokinetic parameters will be derived from analysis of blood samples collected during the first 24 hour infusion.

Clinical Trial Description

Subjects meeting all inclusion and exclusion criteria will be enrolled to receive terameprocol as a weekly 24 hour intravenous infusion, three weeks out of four. Serial measurements of safety will be performed prior to dosing. Subjects will be screened within 28 days of Cycle 1. Hematologic, serum chemistry, tumor marker, and pregnancy testing will be performed. Circulating tumor cell assays will be performed. Needle biopsy specimens will be taken prior to therapy and one week after first dose, if possible, to assess for tumor markers (cdc-2 and survivin). Subjects meeting all inclusion and exclusion criteria will be enrolled in groups of 3-6 subjects to receive terameprocol as a weekly 24 hour intravenous infusion. The terameprocol dose levels to be studied include 100mg/hr, increasing by 25 mg/ hr increments in the next cohort assuming no DLT is reached. Serial measurements of safety will be performed at each visit. The MTD will be assessed after the first Cycle of treatment at a dose level. The use of myeloid colony-stimulating factors will not be allowed prophylactically in cycle 1 but may be used if clinically indicated and will be allowed during subsequent cycles to prevent the development of neutropenia in subjects with an established history of this adverse event in earlier cycles. Each subject in a cohort will be treated at the same dose and on the same schedule of weekly infusions. Dose escalation in a subject may be allowed after safe evaluation of a higher dosage, and two cycles being completed with stable disease or better.

Terameprocol (EM-1421) will be administered as an intravenous infusion over 24 hours, weekly. Dose will commence in the first cohort with 100 mg per hour (2400 mg in a 24 hour period)with escalation in the 5 cohorts of 3 to 6 patients with increments of 25 mg per hour to a maximum of 200 mg/hr (4800 mg/24 hour period) or until MTD is defined. When the MTD has been declared, then 11 additional subjects will be enrolled at the MTD dose level (to total 14 subjects treated in dosage cohort).

Cohort A. will receive weekly Terameprocol 100 mg per hour (2400 mg in a 24 hour period)

Cohort B. will receive weekly Terameprocol 125 mg per hour (3000 mg in a 24 hour period)

Cohort C. will receive weekly Terameprocol 150 mg per hour (3600 mg in a 24 hour period)

Cohort D. will receive weekly Terameprocol 175 mg per hour (4200 mg in a 24 hour period)

Cohort E. will receive weekly Terameprocol 200 mg per hour (4800 mg in a 24 hour period) ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Refractory Solid Tumors

• NCT number: NCT00664586
• Study type: Interventional
• Source: Erimos Pharmaceuticals
• Status: Terminated
• Phase: Phase 1
• Start date: May 2007
• Completion date: June 2009