Clinical trial NCT00106353: Study Evaluating Biomarkers In Relapsed/Refractory Pediatric Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma
Neoplasms
Keywords: Pediatric Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-03-23
Enrollment: 71
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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)


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria:

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).

Exclusion Criteria:

Exclusion Criteria:

* Subjects receiving enzyme-inducing anticonvulsants.
* Pulmonary hypertension or pneumonitis
* Active infection or serious intercurrent illness
* Other exclusions apply

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1
timeFrame: Baseline up to End of Treatment (EOT) (within 30 days of last dose)
measure: Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants Who Died: Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Percentage of Participants With Objective Response (OR) at Week 12: Part 2
timeFrame: Week 12
Secondary outcomes:
measure: Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1
timeFrame: Baseline up to Month 6
measure: Maximum Observed Plasma Concentration (Cmax): Part 1
timeFrame: 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)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1
timeFrame: 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)
measure: Plasma Decay Half-Life (t1/2): Part 1
timeFrame: 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)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1
timeFrame: 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)
measure: Area Under the Concentration-Time Curve (AUC): Part 1
timeFrame: 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)
measure: Clearance (CL): Part 1
timeFrame: 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)
measure: Volume of Distribution at Steady State (Vss): Part 1
timeFrame: 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)
measure: Percentage of Participants With Best Overall Response: Part 1
timeFrame: Baseline until disease progression or recurrence (actual greatest response day is up to Day 49)
measure: Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2
timeFrame: Week 12
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants Who Died: Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2
timeFrame: Baseline up to EOT (within 30 days of last dose)
measure: Maximum Observed Plasma Concentration (Cmax): Part 2
timeFrame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Average Plasma Concentration (Cavg): Part 2
timeFrame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2
timeFrame: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Plasma Decay Half-Life (t1/2): Part 2
timeFrame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2
timeFrame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Area Under the Concentration-time Curve at Steady State (AUCss): Part 2
timeFrame: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Clearance (CL): Part 2
timeFrame: 0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)
measure: Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2
timeFrame: 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)
measure: Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: San Francisco
country: United States
facility: Pfizer Investigational Site
state: California
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: Pfizer Investigational Site
state: Indiana
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: New York
country: United States
facility: Pfizer Investigational Site
state: New York
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Greenville
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Houston
country: United States
facility: Pfizer Investigational Site
state: Texas
city: Seattle
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Calgary
country: Canada
facility: Pfizer Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: Pfizer Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: Pfizer Investigational Site
state: British Columbia
city: Halifax,
country: Canada
facility: Pfizer Investigational Site
state: Nova Scotia
city: London
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Pfizer Investigational Site
state: Ontario
city: Paris Cedex 05
country: France
facility: Pfizer Investigational Site
city: Villejuif
country: France
facility: Pfizer Investigational Site
city: Muenster
country: Germany
facility: Pfizer Investigational Site
city: Mexico City
country: Mexico
facility: Pfizer Investigational Site
city: Lublin
country: Poland
facility: Pfizer Investigational Site
city: Lublin
country: Poland
facility: Pfizer Investigational Site
city: Warszawa
country: Poland
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Moscow
country: Russian Federation
facility: Pfizer Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.