Hepatic ComplicationsPhase 1NCT00275093
Temsirolimus in Treating Patients With Metastatic Solid Tumor or Lymphoma That Cannot Be Removed By Surgery Who Have Different Levels of Liver Function
A Phase 1 study testing temsirolimus, laboratory biomarker analysis and pharmacological study in people with Hepatic Complications and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of temsirolimus in treating patients with metastatic solid tumor or lymphoma that cannot be removed by surgery who have different levels of liver function. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Complications, Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- temsirolimus, 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
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2005to Mar 2008
- 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
- Patients must have histologically or cytologically confirmed solid tumor or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; all solid and lymphoma tumor types are eligible; patients with a liver mass (radiologically evident), elevated alpha-fetoprotein level (>= 500 ng/mL), and positive serology for viral hepatitis or history of alcoholic cirrhosis consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis
- Life expectancy of >= 2 months
- ECOG performance status =< 2 (KPS >= 50)
- Absolute neutrophil count >= 1,000/mcl, and
- Platelets >= 100,000/mcl, and
- Serum creatinine =< 1.5 x ULN OR calculated creatinine clearance >= 60 mL/min/1.73 m^2
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- Patients with abnormal liver function will be eligible and will be grouped according to total bilirubin and AST (SGOT); no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes; for patient stratification, liver function tests should be repeated within 72 hours of starting initial therapy
- Patients with biliary obstruction for which a shunt has been placed are eligible, provided the liver function tests have stabilized (two measurements at least tow days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function); there must be no evidence of biliary sepsis and at least 2 weeks must have elapsed after the placement of a biliary shunt
- Patients receiving medications or substances with the potential to affect the activity the activity or pharmacokinetics of CCI-779 (temsirolimus), such as CYP3A4 substrates, inducers, or inhibitors may be enrolled at the discretion of the investigator; however, consideration should be given to stopping or switching to non-interfering agents if clinically feasible; in all cases, the use of these agents should be listed on the concomitant medication record
- The effects of CCI-779 (temsirolimus) on the developing human fetus and newborn are unknown; for this reason and because CCI-779 (temsirolimus) may be teratogenic, patients must not be pregnant or nursing; men or women of childbearing potential must have agreed to use an effective contraceptive method prior to study entry and for the duration of study participation; since interaction with CCI-779 (temsirolimus) and oral contraceptives is possible, a barrier method should be used and oral contraceptives are not permitted; a negative pregnancy test is required prior to starting therapy for women of childbearing age; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document in accordance with institutional and federal guidelines; all patients must be informed of the investigational nature of this study
- Patients must agree to undergo PK sampling and sample submission as outlined by the protocol
Who cannot join
- Patients who have had chemotherapy, radiotherapy, or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from serious adverse events due to agents administered more than 4 weeks earlier
- Patients with a history of major surgery within 21 days prior to treatment
- Patients may not be receiving any other investigational agents
- Patients must not be planning to receive concurrent radiation, other chemotherapy, or immuno therapy for malignancy while receiving protocol treatment; hormonal treatment for prostate carcinoma may be continued and bisphosphonate treatment for bone disease is permitted
- Patients with unstable or untreated (non-irradiated) brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events; subjects with a prior history of CNS metastases will be eligible if the metastases have been treated with either RT or surgical resection ONLY and subjects are asymptomatic, with stable disease and no longer requiring steroids for at least 2 weeks; a screening magnetic resonance imaging (MRI)/CT (with contrast) is required
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to rapamycin or CCI-779 (temsirolimus)
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- Uncontrolled serious intercurrent medical illness or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because CCI-779 (temsirolimus) is an agent with the potential for teratogenic or abortifacient effects; nursing women are also excluded, as there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CCI-779 (temsirolimus); breastfeeding should be discontinued if the mother is treated with CCI-779 (temsirolimus)
- HIV-positive patients receiving anti-retroviral therapy are excluded from the study due to the possibility of pharmacokinetic interactions with CCI-779 (temsirolimus); however, patients will not routinely be screened for HIV
- Patients who are currently receiving Rapamycin (RAP, Rapamune, Sirolimus) therapy are excluded from the study due to the possibility of overdosing, as CCI-779 is metabolized into sirolimus
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: A Phase I Pharmacokinetic and Pharmacodynamic Study of Temsirolimus (CCI-779) in Patients With Advanced Malignancies and Normal and Impaired Liver Function: An NCI Organ Dysfunction Working Group Study
This phase I trial is studying the side effects and best dose of temsirolimus in treating patients with metastatic solid tumor or lymphoma that cannot be removed by surgery who have different levels of liver function. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Temsirolimus may have different effects in patients who have changes in their liver function
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety, tolerability, and to establish the maximum tolerated recommended dose (RD) CCI-779 (temsirolimus) in cohorts of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) in order to provide appropriate dosing recommendations for CCI-779 (temsirolimus) in this population.
SECONDARY OBJECTIVES:
- To characterize the pharmacokinetic (PK) profile of CCI-779 (temsirolimus) in patients with varying degrees of hepatic function.
II. To determine if the pharmacodynamic (PD) profile of CCI-779 (temsirolimus) as measured by drug effects on p70s6 kinase and p4EBP1 phosphorylation and other markers of mTOR inhibition in peripheral blood mononuclear cells (PBMC) is altered in patients with varying degrees of hepatic function.
III. To document the non-dose limiting toxicities and any anti-tumor efficacy associated with administration of CCI-779 (temsirolimus) in this patient population.
IV. To compare the NCI ODWG criteria and the Child-Pugh classification of hepatic dysfunction in terms of their predictive value in reducing interpatient variability in the PK and PD of CCI-779 (temsirolimus).
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction vs liver transplant).
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temsirolimus 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 dose-limiting toxicity. Up to 12 patients are treated at the MTD.
After completion of study treatment, patients are followed periodically for 30 days.
- Being tested
- temsirolimus, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temsirolimusDrug
Also called CCI-779, cell cycle inhibitor 779, Torisel
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (temsirolimus) | Experimental | Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temsirolimus 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 dose-limiting toxicity. Up to 12 patients are treated at the MTD. Receives: Drug: temsirolimus; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
RD, defined as the highest dose level at which less than 33% of at least six patients experience DLT
Measured: 28 days
Secondary outcomes (4)
PK profile of temsirolimus in patients with varying degrees of hepatic function
Measured: Days 1, 2, 4, 5, 8, 9, 11, 12, 15 of course 1
PD profile of temsirolimus as measured by drug effects on p70s6 kinase phosphorylation in PBMC
Measured: Days 1, 2, 4, and 8 course 1
Incidence of non-dose limiting toxicities
Measured: Up to 30 days
Antitumor efficacy
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2006 (estimated)
- Study startDec 2005
- Primary completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ComplicationsStudies 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
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John Sarantopoulos, Principal investigator, Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00275093
- Sponsor's protocol ID
- NCI-2012-03108
- Other IDs
- 04-04, U01CA069853, U01CA062505, U01CA099168, U01CA062487, U01CA062491, U01CA062502, CDR0000456257
- Status last verified
- Jan 2013
- First submitted
- 10 Jan 2006
- Last updated
- 30 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Pharmacokinetic and Pharmacodynamic Study of Temsirolimus (CCI-779) in Patients With Advanced Malignancies and Normal and Impaired Liver Function: An NCI Organ Dysfunction Working Group Study
- ClinicalTrials.gov ID
- NCT00275093
- Acronym / sponsor ID
- NCI-2012-03108
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2005
- Primary completion
- Mar 2008 (actual)
- First posted
- 11 Jan 2006 (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 phase I trial is studying the side effects and best dose of temsirolimus in treating patients with metastatic solid tumor or lymphoma that cannot be removed by surgery who have different levels of liver function. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Temsirolimus may have different effects in patients who have changes in their liver function
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety, tolerability, and to establish the maximum tolerated recommended dose (RD) CCI-779 (temsirolimus) in cohorts of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) in order to provide appropriate dosing recommendations for CCI-779 (temsirolimus) in this population.
SECONDARY OBJECTIVES:
- To characterize the pharmacokinetic (PK) profile of CCI-779 (temsirolimus) in patients with varying degrees of hepatic function.
II. To determine if the pharmacodynamic (PD) profile of CCI-779 (temsirolimus) as measured by drug effects on p70s6 kinase and p4EBP1 phosphorylation and other markers of mTOR inhibition in peripheral blood mononuclear cells (PBMC) is altered in patients with varying degrees of hepatic function.
III. To document the non-dose limiting toxicities and any anti-tumor efficacy associated with administration of CCI-779 (temsirolimus) in this patient population.
IV. To compare the NCI ODWG criteria and the Child-Pugh classification of hepatic dysfunction in terms of their predictive value in reducing interpatient variability in the PK and PD of CCI-779 (temsirolimus).
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction vs liver transplant).
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temsirolimus 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 dose-limiting toxicity. Up to 12 patients are treated at the MTD.
After completion of study treatment, patients are followed periodically for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (temsirolimus) | Experimental | Drug: temsirolimus, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of temsirolimus 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 dose-limiting toxicity. Up to 12 patients are 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 (12 listed)
- Patients must have histologically or cytologically confirmed solid tumor or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; all solid and lymphoma tumor types are eligible; patients with a liver mass (radiologically evident), elevated alpha-fetoprotein level (>= 500 ng/mL), and positive serology for viral hepatitis or history of alcoholic cirrhosis consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis
- Life expectancy of >= 2 months
- ECOG performance status =< 2 (KPS >= 50)
- Absolute neutrophil count >= 1,000/mcl, and
- Platelets >= 100,000/mcl, and
Key exclusion criteria (10 listed)
- Patients who have had chemotherapy, radiotherapy, or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from serious adverse events due to agents administered more than 4 weeks earlier
- Patients with a history of major surgery within 21 days prior to treatment
- Patients may not be receiving any other investigational agents
- Patients must not be planning to receive concurrent radiation, other chemotherapy, or immuno therapy for malignancy while receiving protocol treatment; hormonal treatment for prostate carcinoma may be continued and bisphosphonate treatment for bone disease is permitted
- Patients with unstable or untreated (non-irradiated) brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events; subjects with a prior history of CNS metastases will be eligible if the metastases have been treated with either RT or surgical resection ONLY and subjects are asymptomatic, with stable disease and no longer requiring steroids for at least 2 weeks; a screening magnetic resonance imaging (MRI)/CT (with contrast) is required
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 |
|---|---|---|
| temsirolimusAlso: CCI-779, cell cycle inhibitor 779, ToriselGiven IV | Drug | Treatment (temsirolimus) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (temsirolimus) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (temsirolimus) |
Primary outcome
RD, defined as the highest dose level at which less than 33% of at least six patients experience DLT
Time frame: 28 days
4 secondary outcomes
PK profile of temsirolimus in patients with varying degrees of hepatic function
Time frame: Days 1, 2, 4, 5, 8, 9, 11, 12, 15 of course 1
PD profile of temsirolimus as measured by drug effects on p70s6 kinase phosphorylation in PBMC
Time frame: Days 1, 2, 4, and 8 course 1
Incidence of non-dose limiting toxicities
Time frame: Up to 30 days
Antitumor efficacy
Time frame: Up to 30 days
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 30 Jan 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.
John Sarantopoulos principal investigator
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
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 temsirolimus, laboratory biomarker analysis and pharmacological study in people with Hepatic Complications and Lymphoma, 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 12 inclusion and 10 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 30 Jan 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?
RD, defined as the highest dose level at which less than 33% of at least six patients experience DLT (time frame: 28 days). 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 30 Jan 2013.