PIb: solid malignancy that is metastatic or unresectable PII: C 1: Advanced metastatic renal cell carcinoma C 2: Advanced low- to intermediate grade metastatic or unresectable locoregional pancreatic neuroendocrine tumors + carcinoid tumors MedDRA version: 9.1 Level: LLT Classification code 10050076 Term: Metastatic renal carcinoma MedDRA version: 9.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor MedDRA version: 9.1 Level: LLT Classification code 10052399 Term: Neuroen
Conditions
Interventions
Product Name: huMab IGF1-R
Product Code: RO4858696/F05
Pharmaceutical Form: Powder for concentrate for solution for infusion
Current Sponsor code: RO4858696
Other descriptive name: R1507 (CHO)
Concent
Sponsors
F.Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. [Phase Ib] Patients must have histologically confirmed recurrent or refractory advanced solid malignancy with no known standard of care according to the judgment of the investigator (including Hodgkin’s and non-Hodgkin’s lymphoma) [Phase II] Patients must have histologically confirmed: • Advanced metastatic renal cell carcinoma (RCC) with evidence of progressive disease despite prior VEGFr- TKI therapy. • Advanced low- to intermediate grade metastatic or unresectable locoregional pancreatic neuroendocrine tumors (pNET) and carcinoid tumors who have failed standard therapy and have evidence of progressive disease. Patients with either carcinoid or islet cell tumors will be included in this cohort. 2. Measurable disease according to RECIST in Phase II 3. Male and female patients, = 18 years age 5. Patients with treated, asymptomatic, stable CNS metastases are eligible for enrollment only if: • Patient has received prior treatment to the site(s) of CNS metastatic disease at least 4 weeks prior to treatment • Patient has no requirement for glucocorticoids (discontinued at least 3 weeks prior to treatment) • Patient is not taking anticonvulsants (discontinued at least 3 weeks prior to treatment) • Patient has no overt evidence of neurological deficit 6. ECOG performance status 0-2 7. Patients must have adequate organ and marrow function 8. Negative pregnancy test (serum ß-HCG) within 7 days of startingStudy treatment in women of childbearing potential (both premenopausal women and women =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with agents that act via inhibition of the IGF-1R pathway. 2. Prior treatment with agents that act via mTOR inhibition (e.g. sirolimus, temsirolimus, everolimus) for the phase II portion only. 3. Patients with untreated CNS metastases. 5. Previous or current anti cancer therapy: Patients who are currently receiving any anti cancer therapy (other than those administered on this study) or who have received: • Radiotherapy = 4 weeks prior to enrollment • Chemotherapy (including biologic therapy) = 4 weeks prior to enrollment • Patients who have received therapy more than 4 weeks prior to enrollment who have not recovered adverse events to = grade 1, (excluding alopecia) 7. History of allogeneic bone marrow transplantation or organ transplantation. 11. Patients who are pregnant or breastfeeding. 12. Fertile men and women of childbearing potential not employing an effective method of birth control throughout the trial and for 3 months after last study drug administration in both sexes. Women of childbearing potential must have a negative pregnancy test (serum ß- HCG) within the 7 days prior to study drug administration. 13. Known hypersensitivity to R1507 or its excipients or to RAD001 or compounds of similar chemical or biologic composition to RAD001. 14. Any known severe and/or uncontrolled medical conditions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: P Ib: • To characterize the safety and tolerability of R1507 administered every 3 weeks in combination with daily RAD001 and to determine the maximum-tolerated dose (MTD) of RAD001 administered orally daily, in combination with R1507 administered intravenously every 3 weeks in patients with advanced solid malignancies, and to determine the recommended dose of RAD001 for the phase II study of the combined regimen. P II: • To assess the clinical activity of combination R1507 and RAD001 in two cohorts of patients, defined by: • PFS rate at 24 weeks, in a cohort of patients with advanced stage renal cell carcinoma [RCC cohort], • PFS rate at 24 weeks, in a cohort of patients with advanced low to intermediate grade metastatic or unresectable locoregional pancreatic neuroendocrine tumors (pNET) and carcinoid tumors, [NET cohort]. • NOTE: the NET cohort will be comprised of equal numbers of patients of 2 tumor subgroups, (pancreatic islet cell tumors and carcinoid tumors);Secondary Objective: Phase Ib: • To describe the tolerability and adverse event profile of the combination of R1507 and RAD001 in patients with advanced solid tumors. • To describe pharmacokinetics (PK) of the combination of RAD001 and R1507 using a population PK approach • To evaluate preliminary anti-tumor activity of the combination. Phase II: • To determine the overall objective response rate, response duration, progression-free survival and overall survival in two cohorts of patients 1) patients with advanced stage renal cell carcinoma (RCC) cohort, and 2) patients with advanced low- to intermediate grade metastatic or unresectable locoregional neuroendocrine tumors (NET) cohort. • To determine the tolerability and adverse event profile of combination R1507 and RAD001 in patients with advanced solid tumors. • To describe pharmacokinetics (PK) of the combination of RAD001 and R1507 using a population PK approach. ;Primary end point(s): The primary endpoints are defined according | — |
Countries
France
Outcome results
None listed