Refractory Solid TumorsPhase 1NCT00664586
A Phase 1 Continuous Intravenous Infusion Study of Terameprocol (EM-1421) in Subjects With Refractory Solid Tumors
A Phase 1 study testing Terameprocol (EM-1421) in people with Refractory Solid Tumors and Lymphoma, run by Erimos Pharmaceuticals at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Solid Tumors, Lymphoma
- What is being tested?
- Terameprocol (EM-1421)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Jun 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects greater than or equal to 18 years of age.
- Subjects who have provided written informed consent to participate in the study.
- 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.
- 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).
- 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.
- No overt cardiac metastasis.
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- Negative pregnancy test if in women of childbearing potential within one week of starting therapy.
- ECOG Performance Status of 0, 1, or 2.
- 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.
Who cannot join
- Subjects meeting any of the following criteria will not be considered eligible for participation in the study:
- 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).
- 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).
- Subjects unable to comply with the study requirements.
- Subjects with a known sensitivity to any of the study medication components.
- 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.
- Subjects with an existing port not compatible with the terameprocol formulation.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
About this study
Official title: A Phase 1 Continuous Intravenous Infusion Study of Terameprocol (EM-1421) in Subjects With Refractory Solid Tumors.
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.
Read the detailed 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)
- Conditions
- Refractory Solid Tumors, Lymphoma
- Being tested
- Terameprocol (EM-1421)
- Keywords
- Terameprocol (EM-1421), Phase 1, Infusion, Refractory Solid Tumors, Lymphoma, Maximum Tolerated Dose, Tumor Response, Tumor Markers, Pharmacokinetics
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Terameprocol (EM-1421)Drug
Also called Terameprocol, EM-1421, meso-Tetra-o-Methyl Nordihydroguaiaretic Acid
Weekly (3 of 4 consecutive weeks) 24 hour continuous intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Terameprocol (EM-1421) | Experimental | 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). Receives: Drug: Terameprocol (EM-1421) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine Maximum Tolerated Dose (MTD)and dose limiting toxicities (DLTs) of Terameprocol (EM-1421) administered as a weekly continuous infusion over 24 hours.
Measured: The MTD will be assessed after the first Cycle of study drug treatment
Secondary outcomes (2)
To further assess the anti-tumor activity of intravenously administered Terameprocol using objective response and duration of response.
Measured: Subjects will be evaluated for response after every 2 cycles (8 weeks) while on study drug.
To assess the pharmacokinetic parameters Terameprocol administered as 24 hour intravenous infusions.
Measured: Pharmacokinetics samples will be taken on Day 1 only: pre-dose and at 1, and 4 hours, 24 hours, 25 hours and 26 hours after first study drug administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2008 (estimated)
- Study startMay 2007
- Primary completionApr 2009
- Study completionJun 2009
Why it stopped: Funding constraints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erimos Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Neil Frazer, MB, ChB, Study director, Erimos Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00664586
- Sponsor's protocol ID
- EM-1421 #104
- Status last verified
- Feb 2016
- First submitted
- 21 Apr 2008
- Last updated
- 23 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Continuous Intravenous Infusion Study of Terameprocol (EM-1421) in Subjects With Refractory Solid Tumors.
- ClinicalTrials.gov ID
- NCT00664586
- Acronym / sponsor ID
- EM-1421 #104
- Conditions
- Refractory Solid Tumors, Lymphoma
- Keywords
- Terameprocol (EM-1421), Phase 1, Infusion, Refractory Solid Tumors, Lymphoma, Maximum Tolerated Dose, Tumor Response, Tumor Markers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding constraints
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Erimos PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 23 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Terameprocol (EM-1421) | Experimental | Drug: Terameprocol (EM-1421)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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female subjects greater than or equal to 18 years of age.
- Subjects who have provided written informed consent to participate in the study.
- 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.
- 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).
- 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.
Key exclusion criteria (7 listed)
- Subjects meeting any of the following criteria will not be considered eligible for participation in the study:
- 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).
- 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).
- Subjects unable to comply with the study requirements.
- Subjects with a known sensitivity to any of the study medication components.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Terameprocol (EM-1421)Also: Terameprocol, EM-1421, meso-Tetra-o-Methyl Nordihydroguaiaretic AcidWeekly (3 of 4 consecutive weeks) 24 hour continuous intravenous infusion | Drug | Terameprocol (EM-1421) |
Primary outcome
To determine Maximum Tolerated Dose (MTD)and dose limiting toxicities (DLTs) of Terameprocol (EM-1421) administered as a weekly continuous infusion over 24 hours.
Time frame: The MTD will be assessed after the first Cycle of study drug treatment
2 secondary outcomes
To further assess the anti-tumor activity of intravenously administered Terameprocol using objective response and duration of response.
Time frame: Subjects will be evaluated for response after every 2 cycles (8 weeks) while on study drug.
To assess the pharmacokinetic parameters Terameprocol administered as 24 hour intravenous infusions.
Time frame: Pharmacokinetics samples will be taken on Day 1 only: pre-dose and at 1, and 4 hours, 24 hours, 25 hours and 26 hours after first study drug administration.
Results and safety
The study was stopped early (reason given: Funding constraints). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2016.
- Related informationLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neil Frazer, MB, ChB study director
Erimos Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Terameprocol (EM-1421) in people with Refractory Solid Tumors and Lymphoma, run by Erimos Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Funding constraints). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. (time frame: The MTD will be assessed after the first Cycle of study drug treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2016.