alle gevorderde maligniteiten, behalve leukemie cancer malignancies
Conditions
Interventions
Eligible patients will be treated with RO5503781, and will follow the study
specific schedule as stated in table 4 (QWx3, page 56 of the study protocol) or
table 5 (QDx5, page 58 of the study protoc
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patient must have histologically or cytologically confirmed advanced malignancies, except all forms of leukemia, for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient.;2. Measureable disease (by RECIST criteria version 1.1 for solid tumors or by Cheson Criteria for malignant lymphomas or evaluable disease prior to the administration of study drug.;3. Patients must be willing to provide archival tumor tissue for biomarker testing (if available). ;4. Ability to understand and the willingness to sign a written informed consent form and comply with all study requirements.;5. Life expectancy of >=12 weeks.;6. Minimum weight of 35 kg.;7. Age >= 18 years.;8. ECOG performance status of 0 to 1.;9. Female patients with child-bearing potential and post menopausal females with less than two years of amenorrhea must have a negative serum pregnancy test within 72 hours of the study first drug administration. ;10. Patient must be willing to use effective methods of contraception. Female patients must be postmenopausal (defined as two years of amenorrhea), surgically sterile, or they must agree to use a physical barrier method of contraception. Oral or injectable contraceptive agents cannot be the sole method of contraception. Male patients must be surgically sterile or agree to use acceptable method of contraception.;Country Specific Requirement for France: All patients must be willing to use effective methods of contraception while receiving study treatment and for 10 days after the last dose of RO5503781. Female patients must be postmenopausal (>=2 years of amenorrhea), surgically sterile, or they must agree to use a physical barrier method of contraception. Oral or injectable contraceptive agents can not be the sole method of contraception. Male patients must be surgically sterile or agree to use acceptable method of contraception.;11. There are no limitations on additional, allowable type and amount of prior anti-tumor therapy. Acute toxicities from any prior anti-tumor therapy, surgery, or radiotherapy must have resolved to NCI-CTCAE Grade = 21 days prior the first administration of study drug RO5503781 (or >=5 x terminal half-life of the therapy for any therapy given less than 21 days previously). ;12. Adequate bone marrow function as defined by:;• ANC of >= 1.5 x 109/L. ;• Platelets count >= lower limit of normal ;• Hemoglobin of >= 9.0 g/dl. ;13. Adequate hepatic function assessed by: ;• Serum total bilirubin = 50 calculated by Cockcroft Gault (if in the PI judgment, serum creatinine level may not adequately reflect renal function). ;15. Patients with stable CNS metastases (have had therapy or don*t require therapy, are off steroids, have no change on screening CT or MRI and are asymptomatic), are eligible. ;16. Patients with chronic, stable and rate-controlled Atrial Fibrillation are eligible.;17. Biomarker Cohorts and Apoptosis Imaging;Cohort ONLY: Patients in consideration for the;biomarker cohort or apopto
Exclusion criteria
Exclusion criteria: 1. Patients with history of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment in addition to their underlying solid tumor.;2. Patients who have received hormonal therapy within the 2 weeks prior to the first dose of study medication. Patients with prostate cancer who are not surgically castrated should remain on GnRH analogues. ;3. Patients who are using other investigational agents or who had received investigational drugs = 2, as per NCI-CTCAE, version 4.03. Treatment for correction of above electrolyte imbalances is permitted during screening to meet eligibility. ;10. Pregnant or breast feeding patients.;11. Patients with reproductive potential not willing to use effective method of contraception.;Country Specific Requirement for France: Patients with reproductive potential not willing to use effective methods of contraception while receiving study treatment and for 10 days after the last dose of RO5503781.;12. HIV-positive patients who are currently receiving combination anti-retroviral therapy.;13. Patients with known coagulopathy, platelet disorder or history of non-drug induced thrombocytopenia.;14. Patients receiving oral or parenteral anticoagulants/antiplatelet agents (e.g. chronic daily treatment with aspirin (> 325 mg/day), clopidogrel or subcutaneous anticoagulant prophylaxis). Patients may receive anticoagulant flushes for maintenance of indwelling catheters.;15. Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products.;16. Patients with known bone marrow disorders which may interfere with bone m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the Maximum Tolerated Dose (MTD) of two different schedules given every 28 days to fasted patients. Characterize the DLTs (dose limited toxicities) and overall safety profile of escalated dose levels of the compound. Explore the two dosing regimens for safety and tolerability. | — |
Secondary
| Measure | Time frame |
|---|---|
| Determine the pharmacokinetic (PK) parameters of the compound (and its major metabolites, if warranted) on two different drug administration schedules. Assess PD effects (in blood, tumor biopsies and molecular imaging) of the compound. Assess any clinical responses. Expand PK evaluation on the weekly schedule (at a dose level below the MTD) for food effect evaluation, PD, and safety data in patients. | — |
Countries
Netherlands
Outcome results
None listed