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
- Conditions
- Ewing’s sarcoma and other sarcoma subtypesMedDRA version: 9.1Level: LLTClassification code 10015560Term: Ewing's sarcoma
- Registration Number
- EUCTR2007-003940-30-FR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 317
1) Patients must have histologically or cytologically confirmed: Ewing’s sarcoma (Ewing’s family of tumors, ESFT); Osteosarcoma ; Synovial sarcoma ; Rhabdomyosarcoma ; Other sarcomas of the following subtypes (Alveolar soft part sarcoma ,Desmoplastic small round cell tumors, Extraskeletal myxoid chondrosarcoma , Clear cell sarcoma ,Myxoid Liposarcoma ).
2) Patients must have had histological verification of malignancy by central pathology review (to be completed within 6 weeks of study entry).
3) All patients must have recurrent or refractory tumors with no known curative treatment options according to the judgment of the investigator. For the Ewing’s and ESFT subtype the disease must be progressive.
4) Age > or =12 years.
5) Life expectancy of at least 6 weeks.
6) Karnofsky performance status of > or =70%
7) Patients must have measurable disease defined as lesions that can be measured in 2 dimensions by medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow disease and lesions seen on PET scan only are not considered measurable.
8) Adequate organ function
8.1 Bone marrow (in the absence of bone marrow involvement by neoplasia)
8.1.1 Absolute neutrophil count > or = 1.5 x 10exp9/L (being > or = 30 days off growth factors
8.1.2 Platelet count > or = 75,000/mL *in patients with documented bone marrow involvement by neoplasia, no minimum ANC or platelet count is necessary at the discretion of the investigator
8.2 Hepatic 8.2.1 Total bilirubin < or = 1.5 times the upper limit of normal for age
8.2.2 ALT /AST (SGPT/SGOT) < or = 3x the ULN for the reference lab (< or = 5 x the ULN for the reference lab in the presence of known hepatic metastasis, adjusted for age)
8.3 Renal
8.3.1 Creatinine clearance > or =70 ml/min/1.73mexp2 or
8.3.2 Serum creatinine < 1.5 x ULN per age.
9) Prior Therapy
9.1 Time elapsed from previous therapy must be > or = 3 weeks. Patients must be recovered from the effects of any prior surgery, radiotherapy or systemic therapy, including any investigational therapy.
9.2 Patients who have undergone autologous hematopoietic stem cell transplantation (HSCT) will be eligible once they have recovered from all toxicities from therapy (< or = grade 1 except for alopecia). Patients who have received allogeneic HSCT will be eligible 6 months after the procedure provided there is no evidence of active graft-versus-host disease and immunosuppressive treatment has been discontinued for at least 30 days.
9.3 Patients with central nervous system (CNS) disease are eligible for enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease, have been off glucocorticoids for at least 4 weeks, have no overt evidence of neurological deficit and are > or = 6 weeks from completion of brain irradiation.
10) Patients or their legal representative must be able to read, understand and provide written informed consent to participate in the trial. Patients younger than 18 years of age should provide assent to participate in the trial.
11) Females of childbearing potential as well as fertile males and their partners must agree to use an effective form of contraception during the study and for 120 days following the last dose of study medication. An effective form of contraception is use of an oral contraceptive, a double barrier method, or commitment to sexual abstinence.
12) Diabetic patients must have well controlled disease. Controlled disease is considered if th
1) Clinically significant unrelated systemic illness (such as serious infections requiring active systemic therapy; cardiovascular disease [congestive heart failure, recent myocardial infarction, unstable angina, inadequately controlled hypertension], poorly controlled diabetes; hepatic renal or other organ dysfunction) which would, in the judgment of the treating physician, compromise the patient’s ability to tolerate the investigational agent or be likely to interfere with the study procedures or results.
2) Known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies (refer to section 8.3 for study drug formulation).
3) Concomitant use of any other investigational agent(s). An investigational therapy is defined as treatment for which there is currently no approved indication from regulatory authorities. Prior use of investigational agent(s) is acceptable if at least 3 weeks have elapsed since last dose and no future doses are planned.
4) Current or previous treatment (within the past 6 months) with chronic, pharmacologic doses of corticosteroids, immunosuppressive agents or medications that inactivate or may interfere with the pharmacologic activity of R1507.
5) Current or prior therapy with IGF inhibitor (monoclonal or specific kinase inhibitor).
6) Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy (post menarche and not post-menopausal, defined as over 12 months since final menstrual period) must have a negative pregnancy test within 7 days prior to first dose.
7) History of solid organ transplant.
8) Other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method