AdenocarcinomaPhase 1/2NCT00106353
Study Evaluating Biomarkers In Relapsed/Refractory Pediatric Solid Tumors
A Phase 1/2 study testing Torisel in people with Adenocarcinoma and Neoplasms, run by Pfizer at 30 sites in 7 countries.
Trial summary
This is an open label, two-part study of temsirolimus given as a 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors… Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Adenocarcinoma, Neoplasms
- What is being tested?
- Torisel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 30 sitesin 7 countries
- Study dates
- Mar 2005to Jan 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Part 1 only:
- Subjects with a histological diagnosis of advanced cancer (solid tumors or central nervous system [CNS] tumors) with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available (histological confirmation waived for brain stem gliomas and optic pathway tumors)
- Part 2 only:
- Subjects with histologically confirmed diagnosis of refractory or relapsed: Neuroblastoma, High-grade gliomas: glioblastoma multiforme, anaplastic astrocytomas, and other high-grade gliomas (histological confirmation waived for brain stem gliomas), Rhabdomyosarcoma.
- Measurable disease (for subjects with neuroblastoma, evaluable disease as determined by a positive metaiodobenzylguanidine (MIBG) scan will also be permitted).
Who cannot join
- Subjects receiving enzyme-inducing anticonvulsants.
- Pulmonary hypertension or pneumonitis
- Active infection or serious intercurrent illness
- Other exclusions apply
Trial locations and contacts
30 sites in 7 countries.
30 sites in 7 countries
United States14 sites
Pfizer Investigational Site
Birmingham, Alabama, 35233
Pfizer Investigational Site
Boston, Massachusetts, 02115
Pfizer Investigational Site
Chicago, Illinois, 60614
Pfizer Investigational Site
Greenville, South Carolina, 29605
Pfizer Investigational Site
Houston, Texas, 77030-2399
Pfizer Investigational Site
Houston, Texas, 77030
Pfizer Investigational Site
Indianapolis, Indiana, 46202
Pfizer Investigational Site
Memphis, Tennessee, 38105-2794
Pfizer Investigational Site
New York, New York, 10032
Pfizer Investigational Site
New York, New York, 11021
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19104-4318
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19104
Pfizer Investigational Site
San Francisco, California, 94143
Pfizer Investigational Site
Seattle, Washington, 98105
Canada6 sites
Pfizer Investigational Site
Calgary, Alberta, T3B 6A8
Pfizer Investigational Site
Edmonton, Alberta, T6G 2B7
Pfizer Investigational Site
Halifax, Nova Scotia, B3K 6R8
Pfizer Investigational Site
London, Ontario, N6A 4G5
Pfizer Investigational Site
Toronto, Ontario, M5G 1X8
Pfizer Investigational Site
Vancouver, British Columbia, V6H 3V4
Poland3 sites
Pfizer Investigational Site
Lublin, 20- 093
Pfizer Investigational Site
Lublin, 20-093
Pfizer Investigational Site
Warsaw, 04-730
Russia3 sites
Pfizer Investigational Site
Moscow, 115478
Pfizer Investigational Site
Moscow, 117513
Pfizer Investigational Site
Saint Petersburg, 197110
France2 sites
Pfizer Investigational Site
Paris, 75248
Pfizer Investigational Site
Villejuif, 94805
About this study
Official title: A Phase I/II Safety and Exploratory Pharmacogenomic/Pharmacodynamic Study of Intravenous Temsirolimus (CCI-779) in Pediatric Subjects With Relapsed/Refractory Solid Tumors
This is an open label, two-part study of temsirolimus given as a 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors.
Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. (recruiting)
- Conditions
- Adenocarcinoma, Neoplasms
- Being tested
- Torisel
- Keywords
- Pediatric Tumors
- Medical subject headings
- Adenocarcinoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToriselDrug
Also called temsirolimus
60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| 1.0 | Experimental | Not described Receives: Drug: Torisel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: Baseline up to End of Treatment (EOT) (within 30 days of last dose)
Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants Who Died: Part 1
Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1
Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1
Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1
Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees Celsius (C), respiratory rate >20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) >200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1
Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Measured: Baseline up to EOT (within 30 days of last dose)
Percentage of Participants With Objective Response (OR) at Week 12: Part 2
Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased >90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.
Measured: Week 12
Secondary outcomes (28)
Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1
Maximum tolerated dose (MTD) defined as the dose level at which >=2 of 3 participants or >=2 of 6 participants if the dose level had been expanded, experienced a dose limiting toxicity (DLT) by day 21 after the first dose of study treatment. DLT defined as failure to recover to NCI-CTCAE version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of > 3 weeks) unless the investigator and the medical monitor agree that the subject should remain in the study.
Measured: Baseline up to Month 6
Maximum Observed Plasma Concentration (Cmax): Part 1
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Plasma Decay Half-Life (t1/2): Part 1
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Concentration-Time Curve (AUC): Part 1
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Clearance (CL): Part 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Volume of Distribution at Steady State (Vss): Part 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Measured: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Percentage of Participants With Best Overall Response: Part 1
Best overall response is the best response recorded from baseline until disease progression or recurrence. Measured as CR, PR, SD, PD, or Unknown. CR=disappearance of all primary and metastatic lesions. PR=at least a 50% decrease in primary disease measurement. SD=no new lesions; decrease of <50% in all lesions with no lesion increasing >25%. PD=any new lesion; at least a 25% increase in any disease measurement (reference smallest disease measurement recorded since start of treatment); or appearance of 1 or more new lesions. Tumor response considered Unknown if assessment prior to Day 37.
Measured: Baseline until disease progression or recurrence (actual greatest response day is up to Day 49)
Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2
Freedom from progression measured as Stable Disease (SD) or better and no Progressive Disease (PD); (CR+VGPR+Mixed Response [MR]+PR+SD). CR=disappearance of all primary and metastatic lesions. VGPR=disappearance of all metastatic lesions. MR=no new lesions; at least 50% decrease in any 1 disease measurement with <50% decrease in any other disease measurement or an increase of <25% in any lesion). SD=no new lesions; decrease of <50% in all lesions with no lesion increasing >25%. PD=at least a 25% increase in any disease measurement; or the appearance of 1 or more new lesions.
Measured: Week 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2
Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2
Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants Who Died: Part 2
Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Temporary interruption of study treatment may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2
Dose reduction for individual participant allowed if a DLT occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2
Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees C, respiratory rate >20 bpm, and systolic and diastolic BP >200/110 mmHg. Participants may be reported in more than 1 category.
Measured: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2
Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Measured: Baseline up to EOT (within 30 days of last dose)
Maximum Observed Plasma Concentration (Cmax): Part 2
Measured: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Average Plasma Concentration (Cavg): Part 2
Measured: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2
Measured: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Plasma Decay Half-Life (t1/2): Part 2
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Measured: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2
AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Measured: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Concentration-time Curve at Steady State (AUCss): Part 2
AUCss is a measure of the serum concentration of the drug at steady state. It is used to characterize drug absorption.
Measured: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Clearance (CL): Part 2
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Measured: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2
Pharmacokinetic parameters determined in whole blood; derived from the concentration-versus-time profiles using noncompartmental analysis method. Measured as nanograms per milliliter (ng/mL).
Measured: Part 1: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2; Part2: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2
Optional bone marrow sampling for pharmacodynamic analysis of effects of study treatment. Data may not be collected for a majority of patients and was not to be summarized if collection was sparse.
Measured: Part 1:Baseline,1,2,6,24,168 hrs post-dose of Cycle 1;additional 0 (Pre-dose),24,72,96 hrs, Day 16 to 21 of cycle 2, EOT(within 30 days of last dose); Part 2:Baseline,Day16 to 21 in Cycle 2, at time of disease progression, EOT(within 30 days of last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2005 (estimated)
- Study startMar 2005
- Primary completionOct 2009
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by PfizerThe 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 1/2
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00106353
- Sponsor's protocol ID
- 3066K1-139
- Status last verified
- Jan 2013
- First submitted
- 22 Mar 2005
- Last updated
- 8 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Geoerger B, Kieran MW, Grupp S, Perek D, Clancy J, Krygowski M, Ananthakrishnan R, Boni JP, Berkenblit A, Spunt SL. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Eur J Cancer. 2012 Jan;48(2):253-62. doi: 10.1016/j.ejca.2011.09.021. Epub 2011 Oct 25.
PubMed 22033322
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Safety and Exploratory Pharmacogenomic/Pharmacodynamic Study of Intravenous Temsirolimus (CCI-779) in Pediatric Subjects With Relapsed/Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT00106353
- Acronym / sponsor ID
- 3066K1-139
- Conditions
- Adenocarcinoma, Neoplasms
- Keywords
- Pediatric Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Mar 2005
- Primary completion
- Oct 2009 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 23 Mar 2005 (estimated)
- Results
- Posted 11 Jan 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, two-part study of temsirolimus given as a 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors.
Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. (recruiting)
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1.0 | Experimental | Drug: Torisel |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Subjects with a histological diagnosis of advanced cancer (solid tumors or central nervous system [CNS] tumors) with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available (histological confirmation waived for brain stem gliomas and optic pathway tumors)
- Subjects with histologically confirmed diagnosis of refractory or relapsed: Neuroblastoma, High-grade gliomas: glioblastoma multiforme, anaplastic astrocytomas, and other high-grade gliomas (histological confirmation waived for brain stem gliomas), Rhabdomyosarcoma.
- Measurable disease (for subjects with neuroblastoma, evaluable disease as determined by a positive metaiodobenzylguanidine (MIBG) scan will also be permitted).
Key exclusion criteria (4 listed)
- Subjects receiving enzyme-inducing anticonvulsants.
- Pulmonary hypertension or pneumonitis
- Active infection or serious intercurrent illness
- Other exclusions apply
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 |
|---|---|---|
| ToriselAlso: temsirolimus60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. | Drug | 1.0 |
Primary outcome
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1
Time frame: Baseline up to End of Treatment (EOT) (within 30 days of last dose)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.
Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Number of Participants Who Died: Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees Celsius (C), respiratory rate >20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) >200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.
Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Percentage of Participants With Objective Response (OR) at Week 12: Part 2
Time frame: Week 12
Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased >90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.
28 secondary outcomes
Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1
Time frame: Baseline up to Month 6
Maximum Observed Plasma Concentration (Cmax): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Plasma Decay Half-Life (t1/2): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Concentration-Time Curve (AUC): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Clearance (CL): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Volume of Distribution at Steady State (Vss): Part 1
Time frame: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Percentage of Participants With Best Overall Response: Part 1
Time frame: Baseline until disease progression or recurrence (actual greatest response day is up to Day 49)
Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2
Time frame: Week 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants Who Died: Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2
Time frame: Baseline up to EOT (within 30 days of last dose)
Maximum Observed Plasma Concentration (Cmax): Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Average Plasma Concentration (Cavg): Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2
Time frame: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Plasma Decay Half-Life (t1/2): Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Area Under the Concentration-time Curve at Steady State (AUCss): Part 2
Time frame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Clearance (CL): Part 2
Time frame: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2
Time frame: Part 1: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2; Part2: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2
Time frame: Part 1:Baseline,1,2,6,24,168 hrs post-dose of Cycle 1;additional 0 (Pre-dose),24,72,96 hrs, Day 16 to 21 of cycle 2, EOT(within 30 days of last dose); Part 2:Baseline,Day16 to 21 in Cycle 2, at time of disease progression, EOT(within 30 days of last dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22033322Geoerger B, Kieran MW, Grupp S, Perek D, Clancy J, Krygowski M, Ananthakrishnan R, Boni JP, Berkenblit A, Spunt SL. Phase II trial of temsirolimus in children with high-grade glioma, neuroblastoma and rhabdomyosarcoma. Eur J Cancer. 2012 Jan;48(2):253-62. doi: 10.1016/j.ejca.2011.09.021. Epub 2011 Oct 25.
Related trials for Adenocarcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruitingPhase 1/2
A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024/LITESPARK-024)
Renal Cell Carcinoma
RecruitingPhase 2
REGULUS: MRI-guided Adaptive SABR for Liver Cancers
Liver Cancer, Intrahepatic Cholangiocarcinoma
RecruitingPhase 1
DBC-664 in Adult Patients With Solid Tumors
Malignant Germ Cell Tumor, Lung Adenocarcinoma
Not yet recruitingPhase 2
Multitargeted Recombinant Ad5 PSA/MUC-1/Brachyury-Based Immunotherapy (TriAdeno) Vaccine With IL-15 Superagonist N-803 in Participants With Clinically Localized Prostate Cancer Undergoing Active Surveillance
Adenocarcinoma, Prostate Cancer
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.
Pfizer CT.gov Call Center study director
Pfizer
30 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Torisel in people with Adenocarcinoma and Neoplasms, run by Pfizer at 30 sites in 7 countries.
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 5 inclusion and 4 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 8 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 30 sites in United States, Canada, Poland, Russia, France and 2 more countries. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 (time frame: Baseline up to End of Treatment (EOT) (within 30 days of last dose)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00106353, which also lists 1 linked publication.
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 8 Feb 2013.