ADVL1221, A Phase II Study of Cixutumumab (IMC-A12; IND# 100947) in Combination with Temsirolimus (IND# 61010) in Pediatric Patients with Recurrent or Refractory Solid Tumors

Summary

The preliminary dosage will be set using data from a previous pediatric study and drug activity will be tested in four sarcoma types of interest. In order to optimize temsirolimus therapy, dosage will be escalated in later treatment courses for patients who do not experience grade 2 or higher mucosistis (ulceration of mucus membranes) or any grade 3 -4 toxicity. A disease cohort will be expanded for further analysis if at least 2 of the first 11 patients experience a partial or complete response. A previous phase II trial of single agent cixutumumab will provide a historical comparison to determine whether there is any benefit of adding temsirolimus.

Cycle 1: Cixutumumab x 6mg/kg
Temsiroliums x 8mg/m2 (maximum dose =16 mg)
Cycle 2: Cixutumumab x 6mg/kg
Temsiroliums x 10mg/m2 (For patients who meet criteria for dose escalation. Maximum dose = 20 mg)
Treatment may be continued for up to 25 cycles, or until distribution of cixutumumab is halted by the manufacturer (expected March 31, 2014).

Participant Eligibility

-- Patients must be between 12 months and 30 years old
-- Patients must be diagnosed with one of the 4 tumors under study and must have relapsed or are refractory to front line therapy. Relapse must be confirmed histologically and archival tumor samples must be available for submission
-- Patients must have radiographically measured disease as defined in the protocol There must be no known curative treatment alternative or other therapy proven to prolong life
-- Patient must be ambulatory Patients must be fully recovered from all prior therapies as indicated in the protocol
-- Patients must have adequate organ function as defined in the protocol
-- Patients with known CNS metastases are excluded unless they have been treated and show no evidence of recurrent lesions for at least 3 months
-- Patients must not be pregnant or breastfeeding (acceptable forms of birth control must be used for patients of child bearing age)
-- Patient must not be receiving any concomitant medications as defined in the protocol
-- Patients must not have any uncontrolled infections
-- Patients with type I or II Diabetes Mellitus are excluded
-- Patients who have previously received IGF-1R or mTOR inhibitors are not eligible Patient must not have had major surgery within 3 weeks prior to enrollment
-- Patient must be able to comply with the safety monitoring requirements of the trial