Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
Condition: Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Childhood Hepatoblastoma; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adrenocortical Carcinoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive; Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Retinoblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors
MeSH terms: Neoplasms; Sarcoma; Neuroblastoma; Osteosarcoma; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Wilms Tumor; Retinoblastoma; Rhabdomyosarcoma, Embryonal; Sarcoma, Synovial; Adrenocortical Carcinoma; Hepatoblastoma; Recurrence
Intervention: cixutumumab; laboratory biomarker analysis
Intervention description: Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.; Correlative studies
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 7 Months
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects and how well cixutumumab works in treating
      patients with relapsed or refractory solid tumors. Monoclonal antibodies, such as
      cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells
      to grow and spread. Others find tumor cells and help kill them or carry tumor-killing
      substances to them.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed malignant solid tumor, including the following:

               -  Osteosarcoma

               -  Ewing sarcoma/peripheral primitive neuroectodermal tumor

               -  Rhabdomyosarcoma

               -  Neuroblastoma

               -  Wilms tumor

               -  Synovial sarcoma

               -  Hepatoblastoma

               -  Adrenocortical carcinoma

               -  Retinoblastoma

          -  No known curative therapy or therapy proven to prolong survival with an acceptable
             quality of life exists

          -  Radiographically measurable disease*, defined as ≥ 1 unidimensionally measurable
             lesion ≥ 20 mm by MRI or CT scan or ≥ 10 mm by spiral CT scan

               -  The following are not considered measurable disease:

                    -  Ascites, pleural effusions, or other malignant fluid collections

                    -  Bone marrow infiltration by tumor

                    -  Lesions detected only by non-MIBG nuclear medicine studies (e.g., bone scan)

                    -  Previously irradiated lesions that have not demonstrated clear progression
                       post-radiotherapy

          -  No known Central Nervous System (CNS) metastases unless they were treated by surgery
             or radiotherapy AND are stable with no recurrent lesions for ≥ 3 months

          -  Lansky or Karnofsky performance status (PS) 50-100% OR Eastern Cooperative Oncology
             Group (ECOG) PS 0-2

          -  Absolute neutrophil count (ANC) ≥ 1,000/mm³ (> 250/mm³ for patients with
             neuroblastoma)

          -  Platelet count ≥ 75,000/mm³ (> 25,000/mm³ for patients with neuroblastoma)
             (transfusion independent)

          -  Hemoglobin ≥ 8.0 g/dL (≥ 7.5 g/dL for patients with neuroblastoma) (RBC transfusion
             allowed)

          -  Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
             creatinine normal based on age/gender as follows:

               -  ≤ 0.4 mg/dL (for patients 1 to 5 months of age)

               -  ≤ 0.5 mg/dL (for patients 6 to 11 months of age)

               -  ≤ 0.6 mg/dL (for patients 1 year of age)

               -  ≤ 0.8 mg/dL (for patients 2 to 5 years of age)

               -  ≤ 1 mg/dL (for patients 6 to 9 years of age)

               -  ≤ 1.2 mg/dL (for patients 10 to 12 years of age)

               -  ≤ 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

               -  ≤ 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

          -  Total bilirubin ≤ 1.5 times upper limit of normal for age

          -  Alanine transaminase (ALT) ≤ 110 U/L

          -  Serum albumin ≥ 2 g/dL

          -  Blood glucose normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 3 months after
             completion of study treatment

          -  Able to comply with safety monitoring requirements of study

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to study drug

          -  No uncontrolled infection

          -  No known type I or II diabetes mellitus

          -  Recovered from prior chemotherapy, immunotherapy, or radiotherapy

          -  More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)

          -  At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)

          -  At least 6 weeks since prior monoclonal antibody therapy

          -  At least 7 days since other prior antineoplastic biologic agents

          -  No prior monoclonal antibody targeting the IGF-IR

          -  No prior small molecule kinase inhibitors of IGF-IR

          -  At least 2 weeks since prior local palliative (small port) radiotherapy

          -  At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or
             radiotherapy to ≥ 50% of the pelvis

          -  At least 6 weeks since other prior substantial bone marrow radiotherapy

          -  At least 2 months since prior stem cell transplantation

               -  No evidence of graft-versus-host disease

          -  Concurrent corticosteroids allowed provided dose is stable or decreasing over the past
             7 days

               -  Intermittent use of corticosteroids to manage infusional reactions allowed

          -  No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
             immunotherapy, or biologic therapy

          -  No other concurrent investigational agents

          -  No concurrent insulin or growth hormone therapy