Protocol Number: 09-C-0054

Title:

A Group Wide Biology and Banking Study for Phase II Study of R1507

Number:

09-C-0054

Summary:

Background:

-R1507 is a recombinant, fully human monoclonal IgG1 antibody that binds specifically to the human IGF-1R, resulting in direct inhibition of ligand binding and loss of receptor protein on the cell surface following intracellular internalization and degradation.

-Binding of R1507 has been shown to inhibit signal transduction and proliferation and survival functions mediated by the IGF-1R in cancer cells. Pre-clinical toxicology and safety pharmacology studies have been performed with R1507 and phase 1 studies in adults have resulted in a recommended intravenous dose of 9 mg/kg weekly. Phase 1 studies are ongoing in children.

-A Phase II study (SARC011/Roche NO21157) A Phase II Trial of R1507, a Recombinant Human Antibody to the Insulin-Like Growth Factor-1 Receptor for the treatment of patients with recurrent or refractory Ewing's sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas will allow an opportunity to collect tumor tissue and serum samples to further characterize the biology of sarcomas and their response to IGF1-R monoclonal antibody therapy.

Objectives:

-To analyze tumor tissue for IGF-1R, phosphor (p)-IGF-1R, Akt, p-Akt, PTEN, and other candidate markers related to the mechanism of action of R1507 in the treatment of patients with sarcoma and other solid tumors.

-To determine whether specific tissue-based assays performed on diagnostic specimens will allow for the identification of newer prognostic categories and potentially new molecular targets for treatment of patients with sarcoma and other solid tumors.

-To determine whether serum levels of, free IGF-I/II, total IGF-I and shed IGF-1R are of significance in the outcome of patients with sarcoma and other solid tumors.

-To identify new treatment targets for therapy. Further testing of these potential targets will be carried out in hopes of expediting translation of these findings to the clinical setting.

Eligibility:

-All patients enrolled on the Phase II study SARC011/Roche NO21157 will be eligible for enrollment.

Design:

-Unstained tumor tissue slides from samples sent for confirmatory diagnosis will be forwarded for further analysis from Central Pathology Labs in New York or Leiden to Roche Clinical Sample Operations (CSO). Tissue based assays to evaluate the status of IGF-1R downstream pathway will be performed by Roche Central Lab (HistoGeneX) and NCI Lab.

-Serum based assays of free serum IGF-I/II, total serum IGF-I and shed IGF-1R receptor will be run using the samples obtained prior to the first dose of R1507 and at specified times during treatment as described in Table 3.3. All serum samples will be shipped to the Roche CSO and forwarded for analysis to the designated laboratories. Serum based assays will be performed by Roche Central Lab (MicroCoat) and Roche Diagnostics (Penzberg).

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

All patients enrolled on the Phase II study SARC011/N021157 will be eligible for enrollment.

Signed informed consent for this study according to institutional guidelines is required.

EXCLUSION CRITERIA:

None.

Special Instructions:

Currently Not Provided

Keywords:

Companion Biology Study

Tissue Collection

Serum Collection

Sarcomas

R1507

Recruitment Keyword(s):

Ewing's Sarcoma

Osteosarcoma

Rhabdomyosarcoma

Synovial Sarcoma

Other Sarcoma

Condition(s):

Ewing's Sarcoma

Osteosarcoma

Rhabdomyosarcoma

Synovial Sarcoma

Other Sarcoma

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, et al. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503-12.

Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000 Jun;21(3):215-44.

Rosen N, Yee D, Lippman ME, Paik S, Cullen KJ. Insulin-like growth factors in human breast cancer. Breast Cancer Res Treat. 1991 May;18 Suppl 1:S55-62.

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