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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Refractory Solid Tumors, Lymphoma

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Trial Information

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


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)


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

To determine Maximum Tolerated Dose (MTD)and dose limiting toxicities (DLTs) of Terameprocol (EM-1421) administered as a weekly continuous infusion over 24 hours.

Outcome Time Frame:

The MTD will be assessed after the first Cycle of study drug treatment

Safety Issue:

Yes

Principal Investigator

Neil Frazer, MB, ChB

Investigator Affiliation:

Erimos Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

EM-1421 #104

NCT ID:

NCT00664586

Start Date:

May 2007

Completion Date:

April 2009

Related Keywords:

  • Refractory Solid Tumors
  • Lymphoma
  • Terameprocol (EM-1421)
  • Phase 1
  • Infusion
  • Refractory Solid Tumors
  • Lymphoma
  • Maximum Tolerated Dose
  • Tumor Response
  • Tumor Markers
  • Pharmacokinetics
  • Lymphoma
  • Neoplasms

Name

Location

The Sarah Cannon Cancer CenterNashville, Tennessee  37203