A PHASE 1/PHASE 2 STUDY OF CP-751,871 IN PATIENTS WITH RELAPSED AND/OR REFRACTORY EWING’S SARCOMA FAMILY OF TUMORS

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 100

Inclusion Criteria

1. Phase 1: Male and female patients 10-18 years old. Phase 2: Male and female patients at least 10 years old. This is multiple center and multinational study. Individual investigators may elect to restrict enrollment to an older age cohort, eg, 13 years old or older, according to local institutional practices; 2. Phase 1 Dose Escalation: Histologically or cytologically confirmed (no new biopsy required) diagnosis of sarcomas including osteosarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, desmoplastic small round cell tumor (DSRCT) or any ESFT, ie, Ewing’s sarcoma, extra-osseous Ewing’s sarcoma, Askin’s and Primitive Neuroectodermal Tumors (PNET); Phase 1 RP2D Extension: Sarcoma patients as defined in the Phase 1 Dose Escalation inclusion criterion. Upon opening of the Phase 2 portion of the study, Ewing’s sarcoma patients with at least one measurable lesion as defined by RECIST will be enrolled in the Phase 2 cohort. Ewing’s sarcoma patients with non RECIST measurable disease may be enrolled in the Phase 1 RP2D Extension cohort; 4. Phase 2: Histologically confirmed (no new biopsy required) ESFT of the bone or soft tissue (Ewing’s sarcoma, extra-osseous Ewing’s sarcoma, PNET and Askin’s tumors); 5. Current disease state for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life; 6. Phase 2 only: Progressive disease with at least one measurable lesion as defined by RECIST; 7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 or a Lansky score >/=80%; 8. Life expectancy of at least 3 months; 9. Adequate recovery from major surgery prior to study treatment. Wound healing must be complete; 10. Adequate bone marrow function documented within 2 weeks prior to treatment, defined as: Absolute Neutrophil Count (ANC) >/=1000/µL; Platelets >/=75,000/µL (Previous transfusion is allowed); Hemoglobin >/=8 g/dL (Previous transfusion is allowed). 11. Adequate renal, hepatic and cardiac functions documented within 2 weeks prior to study treatment, defined as: Total bilirubin /=28% or Ejection Fraction =50%. 12. Phase 1: Prior radiotherapy (at least 1 week prior to enrollment). Phase 2: Prior radiotherapy (at least 1 week prior to enrollment) is allowed provided is not at the only site of measurable disease. A measurable lesion that has been irradiated will beconsidered measurable only when it has increased in size. Patients must have recovered from all acute radiation toxicities (< Grade 1 or deemed irreversible) before enrollment (Prior radiotherapy is not required for inclusion); 13. Fully recovered (< Grade 1 or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study treatment, including a recovery period of a minimum of 2 weeks since previous chemotherapy (8 weeks for mitomycin C or nitrosoureas) and 4 weeks from prior antibody therapy. Recovery from previous investigational therapy must be discussed with the Sponsor; 14. Sexually active female patients must be either postmenopausal or, if of childbearing age, must be surgically sterile or must agree to use effective contraception during the period of therapy and up to 150 days after the last

Exclusion Criteria

Patients presenting with any of the following will not be included in the trial, unless there is a compelling reason which is to be agreed by the investigator and sponsor prior to randomization: 1. Concurrent treatment with any anti tumor agents; 2. Phase 2 only: Prior anti-IGF-IR (anti-insulin like growth factor type 1 receptor) therapy; Patients with symptomatic brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 1 week, and are neurologically stable; 4. Breastfeeding females; 5. Significant active cardiac disease including: uncontrolled high blood pressure (no greater than 2 SD above the mean for age for SBP and DBP), unstable angina, congestive heart failure, valvular disease, endocarditis, myocardial infarction within the previous 6 months, or serious cardiac arrhythmias; 6. Subjects who are receiving chronic high dose immunosuppressive steroid therapy within 2 weeks prior to enrollment (eg, for adults: >/=100 mg prednisone per day or >/=40 mg dexamethasone per day; for children: >20 mg prednisone or >2 mg dexamethasone per day); 7. Active infection; 8. HbA1c>8%; 9. History of malignancies not included in this protocol, within 5 years prior to enrollment, at sites other than curatively treated in situ carcinoma of the cervix, or the uterus, or basal or squamous cell carcinoma of the skin; 10. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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