Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Osteosarcoma

Sarcoma

Sarcoma, Ewing

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Vincristine

Ifosfamide

Etoposide phosphate

Isophosphamide mustard

Doxorubicin

Liposomal doxorubicin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

vincristine, adriamycin and cytoxan, alternating with ifosfamide VP-16

This protocol is designed to test the feasibility of the administration of vincristine, adriamycin and cytoxan, alternating with the newly developed regimen ifosfamide VP-16 as well as the efficacy of this therapy in addition to radiotherapy in producing complete responses and disease-free survival in patients with Ewing's sarcoma, primitive sarcoma of bone, peripheral neuroepithelioma, and soft tissue sarcoma. This will not be a randomized study but will be comparable to the large data base of similar patients treated on successive Pediatric Branch studies.

A Pilot Study for the Treatment of Patients With Metastatic and High Risk Sarcomas and Primitive Neuroectodermal Tumors

National Cancer Institute (NCI)

Rhabdomyosarcoma

Myosarcoma

Eligible patients will be accessioned at the time of irradiation and undergo a pre-radiotherapy evaluation, treatment planning, image-guided radiotherapy delivery and intra-and post-irradiation evaluations.

Conformal limited image radiotherapy is radiation therapy that targets tumors with a prescribed dose of radiation which allows the surrounding normal tissues to remain basically untreated.

image-guided radiotherapy

Matthew Krasin, MD

Researchers at St. Jude Children's Research Hospital are looking for more effective ways to deliver radiation therapy to pediatric tumors of the bone and soft tissues. The goal of the study is to improve local control of musculoskeletal tumors with image-guided radiation therapy (IGRT) while minimizing radiation related side effects. IGRT uses computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) images to precisely define tumor location and to carefully plan radiation treatment. This approach allows doctors to deliver highly conformal radiation therapy to the tumor while protecting nearby healthy normal tissues.

The study focuses on the following primary Objectives:

* To estimate local control rates with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST).

  * Prospectively establish a baseline estimate of local control for patients with MST (Ewing's sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (STS)) treated with image guided radiation therapy.
  * Demonstrate that the increased level of conformality afforded by image guided radiation therapy does not reduce its efficacy relative to previously utilized non-image guided radiation therapy techniques in patients with Ewing's sarcoma family of tumors, resected soft tissue sarcomas, and group III rhabdomyosarcomas.
  * Assess local and regional patterns of failure for patients with MST treated with image guided radiation therapy relative to their targeted volumes.
  * Provide a long term (\>5 year) estimate of local disease control for patients with MST (Ewing's sarcoma family of tumors (ESFT)), rhabdomyosarcoma (RMS), and non-rhabdomyosarcoma soft tissue sarcoma (STS) treated with image guided radiation therapy.

The study focuses on the following secondary objectives:

* Establish a quantitative baseline estimate of radiation dose-related changes in normal tissues using novel objective measures of somatic change, musculoskeletal function, tissue biochemistry and physiology.

  o Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations including:
  * Prospectively investigate whether an age based radiotherapeutic threshold of dose and volume that will induce premature physis closure and alter long bone length can be quantitatively identified.
  * Quantitatively explore the impact of radiation on cortical bone thinning and long bone curvature.
  * Relate radiation dose and volume to late (10+ year) alterations in bone integrity.
* Describe the severity and time course of radiation-induced changes in the soft tissues including muscle.

  * Delineate sequential changes in muscular volume, muscle function and organ function (delineated by imaging and measures of physical function) following image guided radiation for specific muscular groups.
  * Correlate the temporal changes in muscular volume and function with changes in vascularity and metabolism defined by imaging studies.

Radiation Therapy to Treat Musculoskeletal Tumors

Image Guided Radiotherapy for the Treatment of Musculoskeletal Tumors: A Phase II Prospective Evaluation of Radiation-related Treatment Effects

To estimate local control rates with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST).

Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations.

Investigate the dose and volume relationship for the develop8ing physis and cortical bone using physical measures and imaging evaluations.

Describe the severity and time course of radiation-induced changes in the soft tissues and adjacent organs, including muscle and subcutaneous tissues.

Lance Armstrong Foundation

St. Jude Children's Research Hospital

Currently dosing at 20 mg/kg, IV on day 1 of each 28 day cycle until progression or unacceptable toxicity

CP-751,871

Pfizer CT.gov Call Center

This is a phase 1 study of anti-IGF-IR CP-751,871 in patients with solid tumors currently enrolling patients 9 years old and older with Ewing's sarcoma family of tumors (Ewing's, PNET and Askin's).

Study Of Anti-IGF-IR CP-751,871 In Patients With Solid Tumors

Phase 1, Open Label, Multiple Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of CP 751,871 In Patients With Advanced Solid Tumors

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. Treatment-emergent are events between first dose of study drug and up to 150 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Vz 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.

Vz 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. Vss is the Vz at steady-state.

Area under the plasma concentration time-curve from zero to the last measured concentration

Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0 - ∞).

HAHA were indicators of immunogenicity to figitumumab.

Quantification of CTCs using an automated microscope system

Quantification of IGF-IR positive CTCs using an automated microscope system

Pfizer

The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Figitumumab 3 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort.

Figitumumab 3 mg/kg

Figitumumab 6 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort.

Figitumumab 6 mg/kg

Figitumumab 10 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort.

Figitumumab 10 mg/kg

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort.

Figitumumab 20 mg/kg

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for RP2D extension cohort.

Figitumumab 20 mg/kg RP2D

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for RP2D ACC and sarcoma extension cohort.

Figitumumab 20 mg/kg RP2D ACC+Sarcoma

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (4 weeks in duration) for RP2D ESFT extension cohort.

Figitumumab 20 mg/kg RP2D ESFT

Total

Less than (<) 70 years

Equal to or greater than (>=) 70 years

Age, Customized

Sex: Female, Male

The study was completed and 2 participants in figitumumab 20 mg/kg RP2D ESFT group were transitioned to compassionate figitumumab treatment as investigators judged they were receiving benefit from the protocol therapy.

Pfizer ClinicalTrials.gov Call Center

SAEs

All enrolled participants who started treatment.

Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for RP2D, and RP2D ACC and sarcoma extension cohorts.

Figitumumab 20 mg/kg RP2D Every 3 Weeks

All participants treated who had at least 1 of the pharmacokinetic (PK) parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.

Maximum Observed Plasma Concentration (Cmax) in Cycle 1

All participants treated who had at least 1 of the PK parameters of primary interest in extension cohorts. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.

Maximum Observed Plasma Concentration (Cmax) in Cycle 4

All participants treated who had at least 1 of the PK parameters of primary interest. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and figitumumab 20 mg/kg RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: figitumumab 20 mg/kg RP2D every 3 weeks.

Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 1

Time to Reach Maximum Observed Plasma Concentration (Tmax) in Cycle 4

Plasma Decay Half-Life (t1/2) in Cycle 1

Plasma Decay Half-Life (t1/2) in Cycle 4

Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 1

Time to Reach Last Quantifiable Concentration (Tlast) in Cycle 4

Systemic Clearance (CL) in Cycle 1

Systemic Clearance (CL) in Cycle 4

Concentration at End of Infusion (Cendinf) in Cycle 1

Concentration at End of Infusion (Cendinf) in Cycle 4

Volume of Distribution (Vz) in Cycle 1

Volume of Distribution (Vz) in Cycle 4

Volume of Distribution at Steady State (Vss) in Cycle 1

Volume of Distribution at Steady State (Vss) in Cycle 4

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 1

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) in Cycle 4

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] in Cycle 1

All participants treated who had at least 1 of the PK parameters of primary interest in all cohorts except ESFT extension cohort. N=number of participants evaluable for the outcome measure. Summaries for figitumumab 20 mg/kg RP2D, and RP2D ACC and sarcoma extension cohorts were combined into 1 reporting group: 20 mg/kg RP2D every 3 weeks.

Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 1

Area Under the Plasma Concentration-time Profile From Time 0 to 504 Hours (21 Days) (AUC504) in Cycle 4

All participants treated who had at least 1 of the PK parameters of primary interest in RP2D ESFT extension cohort. N=number of participants evaluable for the outcome measure

Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 1

Area Under the Plasma Concentration-time Profile From Time 0 to 672 Hours (28 Days) (AUC672) in Cycle 4

Figitumumab 3, 6, 10, or 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration for dose escalation, RP2D extension, and RP2D ACC and sarcoma extension cohorts, 4 weeks in duration for RP2D ESFT extension cohort).

Figitumumab 3, 6, 10, 20 mg/kg

Per protocol, the presence of HAHA would only be evaluated for those samples with plasma figitumumab concentrations below the limit of quantification (BLQ). Since none of the postdose samples in the study had figitumumab concentrations BLQ, therefore no sample was analyzed for HAHA.

Human Anti-human Antibodies (HAHA) Levels

Figitumumab 3, 6, 10, or 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation and RP2D extension cohorts.

Pretreatment CTCs were detected in an insufficient number of participants to analyze for any treatment effect on this pharmacodynamic biomarker.

Number of Circulating Tumor Cells (CTCs)

Pretreatment IGF-1R positive CTCs were detected in an insufficient number of participants to analyze for any treatment effect on this pharmacodynamic biomarker.

Number of Insulin-like Growth Factor 1 Receptor (IGF-1R) Positive CTCs

Figitumumab 3 milligram/kilogram (mg/kg) was supplied as a liquid solution administered as an intravenous (IV) infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for dose escalation cohort.

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for recommended Phase 2 dose \[RP2D\] extension cohort.

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (3 weeks in duration) for RP2D adrenocortical carcinoma \[ACC\] and sarcoma extension cohort.

Figitumumab 20 mg/kg was supplied as a liquid solution administered as an IV infusion over 2.5 hours (plus or minus 15 minutes) on Day 1 of each cycle (4 weeks in duration) for RP2D Ewing's sarcoma family of tumors \[ESFT\] extension cohort.

Overall Study

Musculoskeletal Diseases

Bone Neoplasms

Andreas Ranft, Dr.

Heribert Jürgens, Prof.

The purpose of the study is to assess the functional outcome, quality of life and late sequelae in a representative sample of 600 long-term survivors of Ewing sarcoma and to build a unique clinical and functional data pool of the underlying cohort of 3000 Ewing sarcoma patients with a follow-up of 3 decades.

Trial objective: As survival rates of bone sarcoma patients have been raised owing to improved treatment strategies the focus of investigations is now on the medical, social, and economic sequelae of intensive multimodal treatment. This study aims to assess the functional outcome, quality of life and late sequelae in a representative sample of long-term survivors of Ewing sarcoma. The data recorded combined with standardized treatment data covering a 30-year period will produce a data pool that is unique for its magnitude and will be used for the development of guidelines for further improvements of future bone sarcoma treatment.

Working plan: The working plan provides for the assessment of functional outcome and quality of life by means of validated tools (TESS, SF36, PEDQOL) and objectively measuring daily activity patterns by using the Step Activity Monitor (SAM) in 600 long-term Ewing sarcoma survivors and a control group of 300 matched healthy subjects. Information on sarcoma treatment and follow-up is obtained by re-structuring and complementing the database of the relevant patient cohort (n=3000) from four consecutive nationwide and international clinical trials between 1980 and 2008. Procedures of local treatment will be evaluated regarding functional outcome, quality of life, and survival probability and prognostic factors predicting long-term outcome will be identified.

Exploitation of results: The results will be presented at scientific meetings and will be published in international journals. Guidelines will be developed regarding improvements in the treatment, rehabilitation, and social integration of bone sarcoma patients to be utilized in guiding patients and in the decision process of medical professionals regarding their treatment. In the long run, the evidence based guidelines on treatment and follow-up are to be transferred into the health system.

Functional and Clinical Long-Term Outcome of Ewing Sarcoma Treatment

German Federal Ministry of Education and Research

University Hospital Muenster

Symptoms and General Pathology

Recurrence

Glioma

Medulloblastoma

Neuroblastoma

Ependymoma

Micronutrients

Hematinics

Vitamins

Pemetrexed

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

1910 milligrams per meter squared (mg/m\^2) (or 60 milligrams per kilogram \[mg/kg\] if patient \<12 months old), intravenous (IV), for 21 days x 17 cycles

pemetrexed

1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

To determine the response rate of pemetrexed given every 21 days for the treatment of children with relapsed or refractory osteosarcoma, Ewing's sarcoma/peripheral primitive neuroectodermal tumors (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET or non-brain stem high-grade glioma.

A Study of Pemetrexed in Children With Recurrent Cancer

A Phase II Study of Pemetrexed in Children With Recurrent Malignancies

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response = disappearance of all target lesions. Partial Response = 30% decrease in sum of longest diameter of target lesions. Response rate (percent \[%\])= (number of participants with complete response (CR) or partial response (PR) in stratum/number of participants in stratum)\*100.

AdEERS= Adverse Event Expedited Reporting System; AE = adverse event. Patients may be counted in more than 1 category. Includes events that were considered possibly related to study drug (PRSD) as judged by the investigator.

The pharmacogenomics outcomes examining the correlation between the presence of the methylene tetrahydrofolate reductase gene and the presence of a polymorphism in the thymidylate synthase (TS) gene and/or gene promoter and toxicity were optional and will not be reported here. Results of this optional research may be reported in the future by the Children's Oncology Group in the peer-reviewed literature.

Children's Oncology Group

Eli Lilly and Company

Chief Medical Officer

Pemetrexed 1910 mg/m2 (or 60 mg/kg if patient \<12 months old)

Pemetrexed 1910 milligrams per meters squared (mg/m\^2) (or 60 milligrams per kilogram \[mg/kg\] if patient \<12 months old)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pilot Study for the Treatment of Patients With Metastatic and High Risk Sarcomas and Primitive Neuroectodermal Tumors	NCT00001209	Neuroectodermal... Neuroepitheliom... Osteosarcoma Sarcoma Sarcoma, Ewing'...	vincristine, ad...	-	National Institutes of Health Clinical Center (CC)
Radiation Therapy to Treat Musculoskeletal Tumors	NCT00186992	Sarcoma, Ewing'... Rhabdomyosarcom... Soft Tissue Sar... Musculoskeletal...	image-guided ra...	- 25 Years	St. Jude Children's Research Hospital
Study Of Anti-IGF-IR CP-751,871 In Patients With Solid Tumors	NCT00474760	Sarcoma, Ewing'...	CP-751,871	9 Years -	Pfizer
Radiation Therapy to Treat Musculoskeletal Tumors	NCT00186992	Sarcoma, Ewing'... Rhabdomyosarcom... Soft Tissue Sar... Musculoskeletal...	image-guided ra...	- 25 Years	St. Jude Children's Research Hospital
Functional and Clinical Long-Term Outcome of Ewing Sarcoma Treatment	NCT00824083	Sarcoma, Ewing'...		6 Years - 60 Years	University Hospital Muenster
Functional and Clinical Long-Term Outcome of Ewing Sarcoma Treatment	NCT00824083	Sarcoma, Ewing'...		6 Years - 60 Years	University Hospital Muenster
A Study of Pemetrexed in Children With Recurrent Cancer	NCT00520936	Osteosarcoma Medulloblastoma Sarcoma, Ewing'... Neuroblastoma (... Neuroblastoma (... Positive Evalua... Rhabdomyosarcom... Ependymoma Non-brainstem H...	pemetrexed	- 22 Years	Eli Lilly and Company
A Study of Pemetrexed in Children With Recurrent Cancer	NCT00520936	Osteosarcoma Medulloblastoma Sarcoma, Ewing'... Neuroblastoma (... Neuroblastoma (... Positive Evalua... Rhabdomyosarcom... Ependymoma Non-brainstem H...	pemetrexed	- 22 Years	Eli Lilly and Company

Spots Global Cancer Trial Database for sarcoma, ewing's