Phase 2 N=19 Treatment

Study Evaluating Biomarkers In Relapsed/Refractory Pediatric Solid Tumors

Adenocarcinoma · Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT00106353 ↗

Enrolled (actual)

Serious AEs

43.7%

Results posted

Jan 2011

Primary outcome: Primary: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 — 4; 5; 3; 7 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Torisel (Drug)
Age: Pediatric, Adult · 1+ yrs
Sex: All
Sponsor: Pfizer
Primary completion: Oct 2009

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1	4; 5; 3; 7; 2; 2	—
PRIMARY Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1	4; 5; 3; 7	—
PRIMARY Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1	1; 2; 2; 4	—
PRIMARY Number of Participants Who Died: Part 1	3; 1; 0; 0; 2; 0	—
PRIMARY Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1	0; 0; 0; 1	—
PRIMARY Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1	0; 2; 1; 2	—
PRIMARY Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1	0; 0; 0; 1	—
PRIMARY Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1	1; 2; 1; 3; 4; 5	—
PRIMARY Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1	4; 5; 3; 7	—
PRIMARY Percentage of Participants With Objective Response (OR) at Week 12: Part 2	0.00; 6.67; 0.00	—
SECONDARY Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1	0; 0; 0; 2	—
SECONDARY Maximum Observed Plasma Concentration (Cmax): Part 1	307; 487; 480; 9230; 252; 403	—
SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1	1; 1.1; 1.3; 1.1; 1.1; 1.7	—
SECONDARY Plasma Decay Half-Life (t1/2): Part 1	10.6; 16.4; 24; 19.3; 14.4; 14.3	—
SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1	1670; 3890; 3750; 9680; 1520; 1930	—
SECONDARY Area Under the Concentration-Time Curve (AUC): Part 1	2000; 4640; 2810; 13000; 1600; 2580	—
SECONDARY Clearance (CL): Part 1	7.02; 10.4; 38.1; 47.9; 8.99; 13.8	—
SECONDARY Volume of Distribution at Steady State (Vss): Part 1	85.2; 189; 783; 512; 250; 201	—
SECONDARY Percentage of Participants With Best Overall Response: Part 1	1; 0; 0; 0; 0; 0	—
SECONDARY Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2	46.67; 40.00; 8.33	—
SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2	17; 19; 16; 10; 6; 6	—
SECONDARY Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2	17; 18; 13	—
SECONDARY Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2	5; 11; 6	—
SECONDARY Number of Participants Who Died: Part 2	5; 2; 4; 3; 0; 3	—
SECONDARY Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2	2; 3; 3	—
SECONDARY Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2	9; 12; 6	—
SECONDARY Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2	5; 10; 6	—
SECONDARY Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2	0; 0; 0; 16; 18; 14	—
SECONDARY Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2	17; 19; 15	—
SECONDARY Maximum Observed Plasma Concentration (Cmax): Part 2	6280	—
SECONDARY Average Plasma Concentration (Cavg): Part 2	82.8	—
SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2	1.00	—
SECONDARY Plasma Decay Half-Life (t1/2): Part 2	30.65	—
SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2	13100	—
SECONDARY Area Under the Concentration-time Curve at Steady State (AUCss): Part 2	13900	—
SECONDARY Clearance (CL): Part 2	14.3	—
SECONDARY Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2	—	—
SECONDARY Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2	—	—

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

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

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00106353). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.