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Investigator(s):
Frank Balis, M.D. Principal Investigator Phone: 301-496-0085 balisf@mail.nih.gov
Referral Contact(s):
Pediatric Oncology  Phone: 1-877-624-4878 (Toll free)

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Primary Eligibility:

• Histologically confirmed solid tumors; brain stem or optic gliomas do not require histological confirmation if biopsy was not performed
• Relapsed after or refractory to standard treatment; no potentially curative treatment options available
• Measurable or evaluable tumors (neuroblastoma only detectable by MIBG or by bone marrow aspirate/biopsy is eligible and considered evaluable disease)
• ≥ 2 and < 18 years of age
• Prior therapy:
• ≥ 2 months post-autologous transplant; ≥ 6 months post-allogeneic transplant and no evidence of active graft-versus-host disease, and off immunosuppressive treatment ≥ 30 days
• ≥ 3 weeks since last dose of myelosuppressive anticancer agents
• ≥ 7 days since last dose of biologic agents to treat cancer and ≥ 30 days since monoclonal antibodies
• ≥ 30 days since last dose of investigational agent
• ≥ 4 weeks since last dose of radiation (including ¹³¹I-MIBG) to > 25% of marrow-containing bones and ≥ 2 weeks since limited port radiation
• ≥ 48 hours since last dose of colony stimulating factors and ≥ 10 days since long acting colony stimulating factors
• Fully recovered to a grade ≤ 1 from toxicities of all prior treatment
• Patients ≥ 10 years of age must have a Karnofsky score of 60–100 and children < 10 years of age must have a Lansky score of 60–100
• ANC ≥ 1.5 x 10⁹/L
• Platelet count ≥ 100 x 10⁹/L
• CD4 count of ≥ 0.2 x 10⁹/L
• Patients with an ANC < 1.5 x 10⁹/L or platelet count < 100 x 10⁹/L are eligible only for the expanded cohort at the optimal dose/maximum tolerated dose (MTD), but will not be evaluable for hematological toxicity; these patients should have an ANC > 0.5 x 10⁹/L and a platelet count > 50 x 10⁹/L
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Age-adjusted normal serum creatinine OR a creatinine clearance ≥ 60 mL/min/1.73 m² based on a 24 hour urine collection
• ALT/AST ≤ 2.5 x the ULN (≤ 5 x the ULN for patients with known hepatic metastases)
• Left ventricle shortening fraction ≥ 28% (or equivalent left ventricular ejection fraction > 45%)
• Patients with CNS metastases if they received prior surgical resection of or radiation to site(s) of CNS disease and have been off corticosteroids for ≥ 2 weeks are eligible; neurological deficits must have been stable ≥ 4 weeks
• Must be willing to participate in the pharmacokinetic studies that are performed on Cycle 1
• No active infection or fever ≥ 38.5° Celsius within 3 days of the first scheduled day of dosing unless fever is tumor-related
• No treatment with pharmacologic doses of corticosteroids within past 2 weeks; current or past use of anti-IGF-1R antibodies; or current treatment with immunosuppressive agents
• No known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies
• No patients with diabetes mellitus defined as casual serum glucose concentration ≥ 200 mg/dL, fasting serum glucose ≥ 125 mg/dL, or use of oral hypoglycemic agent or insulin in order to keep the serum glucose below the above levels
• Not pregnant or nursing; must use effective form of contraception (which includes abstinence) during and for 120 days following last dose of study medication
• No severe uncontrolled systemic disease
• Negative for HIV or hepatitis B or C
• No concurrent treatment with investigational therapy

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Treatment Plan:

This is an open-label, multi-center, sequential groups, Phase I, dose-finding trial of R1507 administered intravenously weekly.

• In the absence of dose-limiting toxicity (DLT), this trial is designed to identify an optimal dose of R1507 defined as the dose that achieves a mean drug exposure (AUC_0-7d) that is equivalent to (at least 85% of) the exposure achieved in adults at the recommended Phase II dose of 9 mg/kg/dose on the weekly dosing schedule
• If DLT is observed in ≥ 2 patients at a dose level, the MTD will be defined
• The first two dose levels are identical to the dose levels in adults
• The third dose level, if necessary, will be calculated to achieve the target AUC, assuming linear pharmacokinetics
• Up to 32 participants will be required to complete the trial

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Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 11/10/08
Updated: 11/3/08