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

• Status: Terminated
• Trial end date: 2009-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erimos Pharmaceuticals
• Treatments: Masoprocol

Criteria

Inclusion Criteria:

1. Male or female subjects greater than or equal to 18 years of age.

2. Subjects who have provided written informed consent to participate in the study.

3. Subjects with documented evidence of cancer with clinically measurable or evaluable disease. Cancer can be recurrent after primary treatment with surgery, radiation therapy and/or chemotherapy and may include those subjects for whom no standard or curative therapy exists.

4. Measurable tumor by imaging (CT per RECIST criteria). unless an established tumor marker exists which can be used for assessment of response in the absence of measurable disease (i.e., PSA in prostate cancer or CA 125 in ovarian cancer).

5. No recent myocardial infarction (within 3 months) or serious intercurrent cardiovascular disease (any event that requires evaluation by a cardiologist, with a definitive cardiac disease diagnosed) Subjects with a history of severe cardiac disease should have had a recent consultation with a cardiologist documenting that there are no new findings.

6. No overt cardiac metastasis.

7. Negative pregnancy test if in women of childbearing potential within one week of starting therapy.

8. ECOG Performance Status of 0, 1, or 2.

9. Absolute neutrophil greater than or equal to 1500 cells/uL, hemoglobin greater than or equal to 9 gm/dl, platelets greater than or equal to 100,000/uL, ALT/AST less than or equal to 3 x ULN (upper limit of the normal range) unless involved with tumor then less than 5 x ULN, bilirubin less than or equal to 1.5 x ULN, creatinine less than or equal to 1.5 x ULN, normal creatinine clearance greater than 60 mL/min and a normal serum bicarbonate. Normal is defined by local laboratory specifications.

Exclusion Criteria:

Subjects meeting any of the following criteria will not be considered eligible for participation in the study:

1. Women who are pregnant or breast-feeding (women of child-bearing potential must have a negative serum pregnancy test within one week of entering the study).

2. Women of child-bearing potential who are unwilling to use two medically acceptable forms of contraception during the course of the study (surgical sterilization, approved hormonal contraceptives, or barrier method with spermicide).

3. Subjects unable to comply with the study requirements.

4. Subjects with a known sensitivity to any of the study medication components.

5. Subjects exhibiting any of the following: a marked baseline prolongation of QT/QTc interval (repeated demonstration of a calculated QTc interval >450), a history of additional risk factors for TdP (e.g. heart failure, hypokalemia, family history of long QT Syndrome), and subjects unable or unwilling to refrain from using medications that are known to prolong the QT/QTc ratio during the course of the study. Subjects having recently taken such medications must have five half-lives off medication before participation.

6. Subjects with an existing port not compatible with the terameprocol formulation.