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SARC 011: A Trial of R1507; A Therapy Targeting the Insulin-Like Growth Factor Pathway |
Dr. Alberto Pappo Professor, Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine; Head of Solid Tumor Program, Texas Children's Cancer Center and Hematology Service; Chair Rare Tumor Committee, Children's Oncology Group; Member, Soft Tissue Sarcoma Committee, Children's Oncology Group
And
Dr. Gilles Vassal Department of Pediatrics, Institut Gustave Roussy; Chairman of Innovative Therapies for Children with Cancer (ITCC)
Trial Background
The insulin-like growth factor (IGF) pathway plays an important role in a variety of physiological processes in humans and animals, including normal growth and development. Additionally, this pathway has been shown to play an important role in the development of conditions like cancer. Recent research as implicated that concentrations of certain components of this pathway are elevated in cancer cells when compared to normal tissues. This is thought to be responsible for cancer cell’s growth and characteristic resistance to cell death that often distinguishes them from surrounding normal tissue. It may also have an important role in mediating the resistance to chemotherapy drugs, hormonal agents, biological therapies, and radiation therapy. Additionally, IGF signaling has been proposed to play a major role in the very aggressive nature of certain sarcomas, like Ewing’s sarcoma family of tumors (ESFT) and synovial sarcomas. It has also been linked to diagnosis of osteosarcoma, liposarcomas and leiomyosarcomas. Although the biological effects of IGF signaling have not been as well explored among many other sarcomas, it is certainly possible that the IGF signaling pathway may also play a significant role among them as well.
In this study, R1507, a human monoclonal antibody, is administered in hopes of slowing tumor growth by blocking specific receptors involved in the IGF pathway.
Results of a Phase I trial of R1507 in patients with solid tumors have just recently been released. In the Phase I study, R1507 was intravenously administered by a weekly infusion. A number of patients with advanced solid tumors experienced a halt in tumor growth and another portion experienced improvement of their condition, with an objective decrease in tumor size (Click here to see published results).
Additionally, weekly administration of R1507 during the Phase I study was well tolerated with very few side effects that are typically experienced with cancer therapy (e.g., low blood counts, infection, hair loss, severe nausea and vomiting). The most frequent side effects observed were fatigue, anorexia and weight loss - all symptoms that are commonly observed in patients with advanced cancer.
The impressive and durable clinical responses in the absence of any significant side affects observed have prompted Roche to propose clinical development of R1507 for the treatment of patients with relapsed or unresponsive Ewing’s sarcoma and other subtypes.
Trial
The primary objective of this Phase II study is to determine the response to R1507 in patients with recurrent or refractory sarcoma of the following subtypes:
(1) Ewing’s sarcoma (Ewing’s family of tumors)
(2) osteosarcoma
(3) synovial sarcoma
(4) rhabdomyosarcoma
(5) other sarcomas of the following subtypes: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, or myxoid liposarcoma.
Trial participants will receive R1507 intravenously (into a vein) once weekly until the patient experiences any intolerable drug related side effects, the cancer has progressed, or voluntary withdrawal.
Participation in the trial*
• 12 years old or older
• Patients must have confirmed diagnosis one of the subtypes listed above
• Patients must have a soft tissue or bone sarcoma that has spread to the point where it is no longer curable by surgery or standard therapy
• The patient must be in good enough condition to be able to care for themselves, but don’t necessarily have to be able to carry on normal activity or to do active work
• Adequate organ function of bone marrow, liver and kidney
• Not pregnant or breastfeeding
• Over three weeks since last administration of any therapy, and patients must be completely recovered from any previous therapy
Patients will have blood tests, a physical exam, and imaging scans before they are enrolled and test results must be within the limits outlined for eligibility to participate in the study protocol.
*this represents only a partial list of requirements to be included or excluded from the study. A complete list is available from SARC or Dr.’s Pappo or Vassal.
For more information contact SARC at 734.930.7600, Dr. Pappo at telephone number (832) 822-4200 or Dr. Vassal at telephone number 33 1 42 11 49 47.
This trial is registered at clinicaltrials.gov at http://www.clinicaltrials.gov/ct2/show/NCT00642941?term=r1507&rank=3
The full title is: SARC Global Collaboration: A Phase II Trial of R1507, a Recombinant Human Monoclonal 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
Glossary:
*monoclonal antibody - A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.
*refractory - Cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment. Also called resistant cancer.
*IGFR-1 Pathway:
*Definitions provided by the NCI cancer glossary. This can be found at http://www.cancer.gov/dictionary/