Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00006242
BMS-214662 in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing BMS-214662, laboratory biomarker analysis and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study the effectiveness of BMS-214662 in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- BMS-214662, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2000to Sep 2005
- 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
- Metastatic or inoperable malignancy, other than leukemia or a primary CNS tumor, for which there is no known curative or survival prolonging palliative therapy, or failure of these therapies
- Life expectancy >= 2 months
- ECOG performance status 0-1
- ANC >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- SGOT and SGPT =< 2.5 times the upper limit of normal (ULN)
Show all 15Show fewer
- Total bilirubin =< ULN
- Serum creatinine =< ULN
- Calculated or measured creatinine clearances (Cockcroft-Gault formula) >= 50 ml/minute
- >= 3 weeks since major surgery
- >= 4 weeks since chemotherapy or radiation therapy
- No uncontrolled serious medical or psychiatric illness
- Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of beta-HCG) within 72 hr prior to receiving the study medication; BMS 214662 has antiproliferative effects which may be harmful to the developing fetus or nursing infant
- Fertile males and females must use adequate contraception
- Signed informed consent
Who cannot join
- Any history of clinically significant atrial or ventricular arrhythmias, any history of second or third degree heart block, or prolonged QTc interval (greater than 450 ms) on electrocardiogram
- Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirement for steroids, or clinical symptoms of/from brain metastases
- Received any drugs within 7 days prior to receiving study drug therapy, which are known to be substrates of cytochrome P450-3A4 (CYP3A4)
- Patients should not receive concurrent therapy with known CYP3A4 substrates while on study and for at least 1 week following the last dose of BMS-214662; this is due to the CYP3A4 inhibitory potential of BMS-214662; a representative list of commonly prescribed known CYP3A4 substrates includes: terfenadine, astemizole, triazolam, midazolam, cisapride, bepridil, rifabutin, simvastatin, lovastatin, and propafenone
- Patients receiving therapy with BMS-214662 should not receive concomitant therapy with NSAIDs or other potentially nephrotoxic medications for at least 2 days before and after administration of BMS-214662
- Patients with known pre-existing renal disease are not eligible
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase I Trial of Farnesyltransferase Inhibitor BMS-214662 (NSC 710086) Escalating to a 24 Hour Continuous Intravenous Infusion in Patients With Solid Tumors
Phase I trial to study the effectiveness of BMS-214662 in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the maximum tolerated dose (MTD) and identify the dose limiting toxicities (DLT) of the investigational agent BMS-214662 when escalated to a 24-hour continuous intravenous infusion every 7 days for 3 consecutive weeks to patients with solid tumors who have failed curative or survival prolonging therapy or for who no such therapies exist.
II. To establish and assess the safety of an appropriate dose for Phase II studies.
III. To characterize the pharmacokinetics of BMS-214662 in patients when escalated to a 24-hour continuous IV infusion.
IV. To assess the extent and duration of farnesyltransferase inhibition in peripheral blood mononuclear cells and other relevant surrogate markers of pharmacological activity.
SECONDARY OBJECTIVES:
- To describe any preliminary evidence of antitumor activity. II. To establish pharmacodynamic relationships for the pharmacological effect of the drug upon surrogate markers of activity and host toxicity.
III. To compare the toxicity profiles for the 1 hour IV infusion and 24 hr continuous IV infusion administration schedules, assuming that the 24 hr infusion schedule is feasible.
OUTLINE: This is a dose-prolongation, dose-escalation study.
Single patient cohorts receive BMS-214662 IV over escalating periods of 2, 4, 8, 16, and 24 hours weekly for 3 weeks followed by 1 week of rest. If no patient experiences dose-limiting toxicity (DLT), dose escalation proceeds in the single patient cohorts.
Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Individual patient cohorts may increase their duration of BMS-214662 infusion in subsequent courses to the current duration safely reached.
Beginning with the infusion level at which DLT is first encountered by a single patient, cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. An additional cohort of 10 patients is treated at the MTD.
Patients are followed for at least 4 weeks.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12 months.
- Being tested
- BMS-214662, laboratory biomarker analysis, pharmacological study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-214662Drug
Also called farnesyltransferase inhibitor BMS-214662, FTI BMS 214662
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (BMS-214662) | Experimental | Single patient cohorts receive BMS-214662 IV over escalating periods of 2, 4, 8, 16, and 24 hours weekly for 3 weeks followed by 1 week of rest. If no patient experiences DLT, dose escalation proceeds in the single patient cohorts.
Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Individual patient cohorts may increase their duration of BMS-214662 infusion in subsequent courses to the current duration safely reached.
Beginning with the infusion level at which DLT is first encountered by a single patient, cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. An additional cohort of 10 patients is treated at the MTD. Receives: Drug: BMS-214662; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of BMS-214662, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Measured: Up to 28 days
Adverse events, based on the NCI CTC v2.0
Measured: Up to 5 years
Plasma concentration-time profile of BMS-214662 when given as a continuous IV infusion escalating to 24 hr
Measured: Up to 48 hours
Secondary outcomes (4)
Determination whether the pharmacokinetic behavior is linear as dose is escalated
Measured: Up to 48 hours
Determination of dose that provides potentially effective level of systemic exposure to the drug as indicated by information from preclinical studies
Measured: Up to 48 hours
Interpatient variability in the steady state plasma concentration (C^ss) and other pharmacokinetic variables in patients treated at the MTD peak
Measured: Up to 48 hours
Correlations between pharmacokinetic variables and pretreatment laboratory values, toxicity, and indications of biological response (farnesyltransferase activity)
Measured: Up to 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2003 (estimated)
- Study startJul 2000
- Primary completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joseph Eder, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006242
- Sponsor's protocol ID
- NCI-2013-00032
- Other IDs
- 00-003, U01CA062490, CDR0000068170
- Status last verified
- Jan 2013
- First submitted
- 11 Sep 2000
- Last updated
- 1 Feb 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Farnesyltransferase Inhibitor BMS-214662 (NSC 710086) Escalating to a 24 Hour Continuous Intravenous Infusion in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT00006242
- Acronym / sponsor ID
- NCI-2013-00032
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2000
- Primary completion
- Sep 2005 (actual)
- First posted
- 22 May 2003 (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.
Phase I trial to study the effectiveness of BMS-214662 in treating patients who have advanced solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die
Detailed description
PRIMARY OBJECTIVES:
- To establish the maximum tolerated dose (MTD) and identify the dose limiting toxicities (DLT) of the investigational agent BMS-214662 when escalated to a 24-hour continuous intravenous infusion every 7 days for 3 consecutive weeks to patients with solid tumors who have failed curative or survival prolonging therapy or for who no such therapies exist.
II. To establish and assess the safety of an appropriate dose for Phase II studies.
III. To characterize the pharmacokinetics of BMS-214662 in patients when escalated to a 24-hour continuous IV infusion.
IV. To assess the extent and duration of farnesyltransferase inhibition in peripheral blood mononuclear cells and other relevant surrogate markers of pharmacological activity.
SECONDARY OBJECTIVES:
- To describe any preliminary evidence of antitumor activity. II. To establish pharmacodynamic relationships for the pharmacological effect of the drug upon surrogate markers of activity and host toxicity.
III. To compare the toxicity profiles for the 1 hour IV infusion and 24 hr continuous IV infusion administration schedules, assuming that the 24 hr infusion schedule is feasible.
OUTLINE: This is a dose-prolongation, dose-escalation study.
Single patient cohorts receive BMS-214662 IV over escalating periods of 2, 4, 8, 16, and 24 hours weekly for 3 weeks followed by 1 week of rest. If no patient experiences dose-limiting toxicity (DLT), dose escalation proceeds in the single patient cohorts.
Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Individual patient cohorts may increase their duration of BMS-214662 infusion in subsequent courses to the current duration safely reached.
Beginning with the infusion level at which DLT is first encountered by a single patient, cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. An additional cohort of 10 patients is treated at the MTD.
Patients are followed for at least 4 weeks.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (BMS-214662) | Experimental | Drug: BMS-214662, Other: laboratory biomarker analysis, Other: pharmacological studySingle patient cohorts receive BMS-214662 IV over escalating periods of 2, 4, 8, 16, and 24 hours weekly for 3 weeks followed by 1 week of rest. If no patient experiences DLT, dose escalation proceeds in the single patient cohorts. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Individual patient cohorts may increase their duration of BMS-214662 infusion in subsequent courses to the current duration safely reached. Beginning with the infusion level at which DLT is first encountered by a single patient, cohorts of 3-6 patients receive escalating doses of BMS-214662 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. An additional cohort of 10 patients is treated at the MTD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Metastatic or inoperable malignancy, other than leukemia or a primary CNS tumor, for which there is no known curative or survival prolonging palliative therapy, or failure of these therapies
- Life expectancy >= 2 months
- ECOG performance status 0-1
- ANC >= 1,500/mm^3
- Platelets >= 100,000/mm^3
Key exclusion criteria (6 listed)
- Any history of clinically significant atrial or ventricular arrhythmias, any history of second or third degree heart block, or prolonged QTc interval (greater than 450 ms) on electrocardiogram
- Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirement for steroids, or clinical symptoms of/from brain metastases
- Received any drugs within 7 days prior to receiving study drug therapy, which are known to be substrates of cytochrome P450-3A4 (CYP3A4)
- Patients should not receive concurrent therapy with known CYP3A4 substrates while on study and for at least 1 week following the last dose of BMS-214662; this is due to the CYP3A4 inhibitory potential of BMS-214662; a representative list of commonly prescribed known CYP3A4 substrates includes: terfenadine, astemizole, triazolam, midazolam, cisapride, bepridil, rifabutin, simvastatin, lovastatin, and propafenone
- Patients receiving therapy with BMS-214662 should not receive concomitant therapy with NSAIDs or other potentially nephrotoxic medications for at least 2 days before and after administration of BMS-214662
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 |
|---|---|---|
| BMS-214662Also: farnesyltransferase inhibitor BMS-214662, FTI BMS 214662Given IV | Drug | Treatment (BMS-214662) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (BMS-214662) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (BMS-214662) |
Primary outcome
Maximum tolerated dose (MTD) of BMS-214662, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time frame: Up to 28 days
Adverse events, based on the NCI CTC v2.0
Time frame: Up to 5 years
Plasma concentration-time profile of BMS-214662 when given as a continuous IV infusion escalating to 24 hr
Time frame: Up to 48 hours
4 secondary outcomes
Determination whether the pharmacokinetic behavior is linear as dose is escalated
Time frame: Up to 48 hours
Determination of dose that provides potentially effective level of systemic exposure to the drug as indicated by information from preclinical studies
Time frame: Up to 48 hours
Interpatient variability in the steady state plasma concentration (C^ss) and other pharmacokinetic variables in patients treated at the MTD peak
Time frame: Up to 48 hours
Correlations between pharmacokinetic variables and pretreatment laboratory values, toxicity, and indications of biological response (farnesyltransferase activity)
Time frame: Up to 48 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2013.
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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.
Joseph Eder principal investigator
Dana-Farber Cancer Institute
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 BMS-214662, laboratory biomarker analysis and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) 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 15 inclusion and 6 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: finished, as of the sponsor's last update on 1 Feb 2013. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose (MTD) of BMS-214662, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (time frame: Up to 28 days). The study lists 3 primary outcomes in all. 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 1 Feb 2013.