Advanced or Metastatic Solid Tumors
Conditions
Brief summary
VELCADE has demonstrated marked activity in haematological cancers leading to registration (MM, MCL). Currently only biweekly or weekly regimens have been explored. Key signalling pathways which are aberrant in haematological cancers are also present in solid tumors. VELCADE covers a broad spectrum of proteins, which are pivotal in carcinogenesis.VELCADE as a single agent & in combination with chemotherapy in solid cancers has shown modest and real anti-tumor activity but insufficient for Phase III development. VELCADE PK exposure may be inadequate in solid tumors compared to "liquid cancers." VELCADE daily low dose administration may allow a greater PK exposure to be achieved, which is tolerated Hypotheses: VELCADE daily dosing (5-days on, 2-days off) is tolerable at biologically active doses VELCADE daily dosing (5-days on, 2-days off) results in increased PK (AUC)/PD (20S proteasome inhibition) VELCADE daily dosing (5-days on, 2-days off) with increased PK/PD results in improved anti-tumor activity (Increased tolerable VELCADE AUC may potentially cross the threshold required for clinically significant anti-tumor activity in solid cancers). Some preclinical data suggest that: VELCADE daily dosing results in increased proteasome inhibition in tumor tissues Combination of VELCADE + XRT/other daily dosing agent may have increased anti-tumor activity compared to monotherapy alone.
Interventions
DRUGBortezomib
Sponsors
Gustave Roussy, Cancer Campus, Grand Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent 2. Target population * Subjects with advanced or metastatic solid tumors for whom the standard of care is ineffective or inappropriate * Ability to comply with visits/procedures required by the protocol * Life expectancy of at least 3 months * ECOG performance status score 0-1 * Subjects with Histologic or cytologic diagnosis of any solid tumor (nonhematologic malignancy). * A tumor paraffin tissue block or 20-30 unstained slides from the tumor tissue block or enough slides from an FNA to allow for biomarker and predictive marker analyses. (This biopsy need not be obtained fresh at the time of screening. Obtaining unstained slides from the original diagnostic biopsy will suffice to meet this requirement). * Measurable or evaluable disease * Prior anti-cancer treatments are permitted (i.e. chemotherapy, radiotherapy, hormonal, or immunotherapy) with the following exceptions: * Toxicity related to prior therapy must either have resolved, returned to baseline or been deemed irreversible but does not conflict with
Exclusion criteria
. Peripheral pre-existent neuropathy of any grade related or not related to previous anticancer therapy is an exclusion criterion. * At least 3 weeks must have elapsed since the last chemo-therapy, immunotherapy or radiotherapy and the beginning of protocol therapy. At least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin. * At least 3 weeks must have elapsed since the last anti-cancer hormonal therapy or antibody targeted therapy (e.g. Bevacizumab, Cetuximab, Trastuzumab). Hormonal treatment by analog LHRH will be allowed for patients with prostate cancer For extended-release formulations, the washout period must extend 1 month beyond the duration of activity of the formulation (e.g., 3 months for the activity of a depot formulation + 1 month wash out). 3. Age and Sex * men and women 18 - 75 * Male and female patients of childbearing potential must use effective contraceptive measures during the study an d for at least 3 months after the end of the study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Identify maximum tolerated dose | Assessed every week from inclusion during the first 28 days and then every 28 days up to 19 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy | Assessed within 7 days of every cycle (28 days) up to 19 months | According to the WHO criteria for tumor response |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORRastislav BAHLEDA, MD
Gustave Roussy, Cancer Campus, Grand Paris
Outcome results
None listed