weke delen Soft Tissue Sarcoma
Conditions
Interventions
In both parts of the study, doxorubicin will be administered on day 1 of each
21-day cycle, followed by AMG 655 (part 1
part 2, arm A) or placebo (part 2
arm B). No more than 6 cycles of doxorubicin will be given. AMG 655 or placebo
monotherapy may continue after doxorubicin has been discontinued, until disease
prog
Sponsors
Amgen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Histologically or cytologically confirmed soft tissue sarcoma Locally advanced, recurrent, or metastatic, unresectable disease Intermediate or high grade disease (grade 2 or 3 according to the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading sysem)
Exclusion criteria
Exclusion criteria: The following tumor types ar not eligible: Alveolar soft part sarcoma, Clear cell sarcoma (melanoma of soft parts), Chondrosarcoma, Desmoid tumor, Desmoplastic small round cell tumor, Embryonal rhabdomyosarcoma, Ewing sarcoma / Primitive neuroectodermal tumor (PNET), Gastrointestinal stroma tumor (GIST), Kaposi sarcoma, Mesothelioma, Mixed mesodermal tumor, Neuroblastoma, Osteosarcoma. History or known presence of uncontrolled central nervous system (CNS) metastasis Prior Chemotherapy or investigational agent(s) for the treatment of locally advanced or metastatic, unresectable soft tissue sarcoma (prior neo-adjuvant or adjuvant therapy is allowed, provided there was no disease progression with 6 months after completion of treatment)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1 (phase 1b): To identify a dose of AMG 655 in combination with doxorubicin that is safe and tolerated as determined by the incidence of dose limiting toxicity. Part 2 (phase 2): To estimate the efficacy, as measured by progression-fee survival, AMG 655 at the dose selected in part 1, in combination with doxorubicin. | — |
Secondary
| Measure | Time frame |
|---|---|
| To estimate the clinical benefit of AMG 655 in combination with doxorubicin, as measured by objective response rate, time to response, duration of response, clinical benefit rate (complete response, partial response, and disease stabilization more or equal to 12 weeks, as measured by modified response evaluation criteria in solid tumors, progression-free survival (part 1), and overall survival. To evaluate the safety and tolerability of AMG 655 in combination with doxorubicin (part 2) To evaluate anti-AMG 655 antibody formation To evaluate the pharmacokinetics of AMG 655 (part 1; selected sites in part 2) Exploratory: To investigate the objective response rate and progression fee survival in subjects treated with AMG 655 monotherapy, after disease progression on doxorubicin plus placebo (part 2, arm B) To investigate the relationship between AMG 655 pharmacokinetics and treatment outcomes (including tumor response and pharmacodynamic endpoints) To investigate the pharmacodynamics response to AMG 655 in combination with doxorubicin, as assessed by apoptosis biomarkers (caspase 3/7, genomic DNA levels; part 1; selected sites in part 2), and correlate with treatment outcomes To investigate other potential biomarker development (e.g., biochemical levels and abundance of drug targets) by biochemical analysis of blood and/or tumor tissue, and correlate with treatment outcomes To investigate the genetic variation in drug metabolism genes, cancer genes, and drug target genes, and correlate with treatment outcomes (optional; requires separate informed consent) To estimate the effect of AMG 655 on patient reported outcomes pertaining to cancer-related and treatment-related symptoms and health-related quality of life based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30. To estimate the time to improvement in cancer-related symptoms based on European Organization for Research and Treatment of C | — |
Countries
Netherlands
Outcome results
None listed