Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Sarcoma, Ewing

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Final dose 30 mg/kg IV on Day 1 of each 28 day cycle until either progression or toxicity

CP-751,871

Pfizer CT.gov Call Center

Define the efficacy of CP-751,871 in patients with Ewing's sarcoma family of tumors

Study Of CP-751,871 In Patients With Ewing's Sarcoma Family Of Tumors

A Phase 1/Phase 2 Study Of CP-751,871 In Patients With Relapsed And/Or Refractory Ewing's Sarcoma Family Of Tumors

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as complete disappearance of all target and non-target disease and no new lesions. PR was defined as ≥30% decrease under baseline of the sum of diameters of all target lesions.

PFS was the time in months from start date to date of first documentation of progression, death due to any cause or symptomatic deterioration (global deterioration of health status requiring discontinuation of treatment).

Time in months from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

Cmin is the concentration at the end of treatment cycle (next cycle predose).

The dosing interval was 1 cycle (4 weeks) in this study.

AUClast is the area under the plasma concentration time-curve from zero to the last measured concentration.

Number of participants with positive sample(s) in the ADA assay and in the neutralizing anti-drug antibodies (NAb) assay. An endpoint titer \<6.64 corresponded to negative ADA category value.

Pfizer

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

Figitumumab 20 mg/kg IV was administered every 4 weeks (1 cycle).

Figitumumab 20 mg/kg Dose Escalation (Phase 1)

Figitumumab 30 mg/kg IV was administered every 4 weeks (1 cycle).

Figitumumab 30 mg/kg Dose Escalation (Phase 1)

Figitumumab 30 mg/kg Dose Extension (Phase 1B)

Figitumumab 20 mg/kg IV was administered every 4 weeks (1 cycle). As optional salvage therapy for disease progression, oral rapamycin at 2 to 4 mg/day was administered in combination with figitumumab.

Figitumumab 20 mg/kg + Rapamycin Dose Escalation (Phase 1)

Figitumumab 30 mg/kg IV was administered every 4 weeks (1 cycle). As optional salvage therapy for disease progression, oral rapamycin at 2 to 4 mg/day was administered in combination with figitumumab.

Figitumumab 30 mg/kg + Rapamycin Dose Escalation (Phase 1)

Figitumumab 30 mg/kg + Rapamycin Dose Extension (Phase 1B)

Figitumumab 30 mg/kg IV was administered every 4 weeks (1 cycle) until unacceptable toxicity or participant withdrawal, for up to 6 cycles.

Figitumumab 30mg/kg (Phase 2)

Figitumumab 30 mg/kg + Rapamycin (Phase 2)

Figitumumab 20 milligrams per kilogram (mg/kg) intravenous (IV) administered every 4 weeks (1 cycle). If no dose-limiting toxicity (DLT) was identified in the 20-mg/kg cohort, dose escalation proceeded to 30-mg/kg. Oral rapamycin at 2 to 4 mg/day could have been added as salvage therapy.

Figitumumab Dose Escalation (Phase 1)

Figitumumab 20 mg/kg or 30 mg/kg IV administered every 4 weeks (1 cycle). Oral rapamycin at 2 to 4 mg/day could have been added as salvage therapy.

Figitumumab Dose Extension (Phase 1B)

Figitumumab 30 mg/kg IV administered every 4 weeks (1 cycle) for up to 12 cycles, unless unacceptable toxicity or participant withdrawal. Oral rapamycin at 2 to 4 mg/day could have been added as salvage therapy.

Figitumumab 30 mg/kg (Phase 2)

Total

10 to <13 years

13 to <=18 years

18 to <30 years

30 to <41 years

>=41 years

Age, Customized

Sex: Female, Male

Pfizer ClinicalTrials.gov Call Center

All enrolled participants with Ewing's sarcoma family of tumors (ESFT) and who started treatment with figitumumab; number of evaluable participants at data cut-off.

Objective Response Rate (ORR)

All enrolled participants with ESFT and who started treatment with figitumumab.

Progression-Free Survival (PFS)

Overall Survival (OS)

Cycle 1 (n=4, 6, 21)

Cycle 5 (n=2, 2, 8)

The pharmacokinetic (PK) analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; n=number of participants evaluable for this measure at specified time points for each arm group, respectively.

Maximum Observed Plasma Concentration (Cmax)

The PK analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; number of participants evaluated for measure.

Minimum Observed Plasma Trough Concentration (Cmin)

The PK analysis set included all enrolled participants who started treatment and who had sufficient samples to provide interpretable results; n=number of participants evaluable for this measure at specified time points for each arm group, respectively.

Plasma Concentration at End of Infusion (Cendinf)

Figitumumab 20 mg/kg IV administered every 4 weeks (1 cycle).

Figitumumab 30 mg/kg IV administered every 4 weeks (1 cycle).

Figitumumab 30 mg Dose Escalation (Phase 1)

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)

Cycle 1 (n=3, 5, 16)

Cycle 5 (n=1, 1, 6)

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

All enrolled participants with ESFT and who started treatment with figitumumab. None of the serum samples were positive for ADAs following repeated administration of figitumumab, as indicated by an endpoint titer of \<6.64.

Number of Participants With Positive Anti-Drug Antibody (ADA) Titer

Phase 1

Phase 1B

Phase 2

Rhabdomyosarcoma

Myosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Doxorubicin

Liposomal doxorubicin

Previously untreated patients referred to St. Jude Children's Research Hospital (SJCRH) between the ages of 0 and 21 years with a diagnosis of osteosarcoma, ESFT, rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes administration of a cumulative anthracycline dose ≥ 375 mg/m2.

Daniel Green, MD

Anthracycline antibiotics are included in the chemotherapy regimens of approximately 82% of patients with bone cancer and 44% of those with soft tissue sarcoma diagnosed in childhood or adolescence. Impaired cardiac function occurs after treatment with anthracyclines. The frequency of impairment increases with increasing cumulative dose. There are inadequate data regarding the relationship between doxorubicin administration and changes in serum levels of cardiac troponin T (cTn-T) or I (cTn-I), N-terminal (NT) brain natriuretic peptide (BNP), or tissue Doppler imaging parameters.

This non-therapeutic study proposes a prospective, single arm study of serial changes in tissue Doppler imaging parameters, cTn-T and NT-BNP in children and adolescents with malignant bone and soft tissue tumors whose planned chemotherapy includes treatment with ≥ 375 mg/m2 of doxorubicin.

The proposed study will rigorously evaluate the usefulness of serial determinations of tissue Doppler imaging, cTn-T and NT-BNP for very early identification of anthracycline-related myocardial injury. Demonstration that one or more of these markers identifies subclinical myocardial damage and that biomarker or tissue Doppler imaging parameters exhibit a dose-response relationship with cumulative doxorubicin dose would facilitate intervention trials in patients at risk for anthracycline cardiomyopathy.

The primary aim of this proposal is to serially evaluate imaging tests in previously untreated patients with osteosarcoma, Ewing's Sarcoma Family of Tumors(ESFT), rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes a cumulative doxorubicin dose ≥ 375 mg/m2 to determine if serial levels of one or more of these potential markers of cardiac muscle injury obtained prior to each infusion of doxorubicin and at the completion of chemotherapy correlate with increasing cumulative anthracycline exposure.

The secondary aim of the study is to estimate the proportion of patients with decreased (evaluation j - evaluation j+1) peak longitudinal systolic strain (ε) or strain rate (SR), peak radial systolic ε or SR, peak radial systolic myocardial velocity or peak longitudinal systolic myocardial velocity among those who have a shortening fraction (SF) ≥ 29% prior to each infusion of anthracycline. This study will evaluate whether the serum levels of cTn-T and/or NT-BNP will increase following doxorubicin administration. The study will evaluate whether the serum levels of cTn-T and/or NT-BNP will increase with increasing cumulative doxorubicin dose.

A blood sample will be collected at baseline, prior to and at the end of each doxorubicin infusion (48- or 72-hour) and following completion of chemotherapy for osteosarcoma, ESFT, rhabdomyosarcoma or intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas.cTn-T and NT-BNP will be measured at baseline, prior to and at the end of each doxorubicin infusion (48- or 72-hour) and following completion of chemotherapy for osteosarcoma, ESFT, rhabdomyosarcoma or intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas.

Markers of Anthracycline-Related Cardiac Muscle Injury

This study will serially evaluate imaging tests in previously untreated patients with osteosarcoma, Ewing's sarcoma family of tumors, rhabdomyosarcoma and intermediate and high-risk non-rhabdomyosarcoma soft tissue sarcomas whose planned treatment includes a cumulative doxorubicin dose ≥ 375 mg/m2 to determine if serial levels of one or more of these potential markers of cardiac muscle injury obtained prior to each infusion of doxorubicin and at the completion of chemotherapy correlate with increasing cumulative anthracycline exposure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Of CP-751,871 In Patients With Ewing's Sarcoma Family Of Tumors	NCT00560235	Ewing's Sarcoma...	CP-751,871	10 Years -	Pfizer
Study Of CP-751,871 In Patients With Ewing's Sarcoma Family Of Tumors	NCT00560235	Ewing's Sarcoma...	CP-751,871	10 Years -	Pfizer
Markers of Anthracycline-Related Cardiac Muscle Injury	NCT01112800	Osteosarcoma Ewing's Sarcoma... Rhabdomyosarcom... Non-rhabdomyosa...		- 21 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for ewing's sarcoma family of tumors