Advanced or Metastatic Solid Malignancy Clinical Trial
Official title:
Clinical Evaluation of the Underlying Mechanisms of Targeted Therapy Related Toxicities
Verified date | April 2017 |
Source | VU University Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
Single center, non-randomized, interventional pilot study with feasibility analysis after enrollment of 20 patients. Adult patients with advanced solid tumors, for whom standard palliative treatment with targeted agents as monotherapy is indicated, including antiangiogenic tyrosine kinase inhibitors, EGFR inhibitors, mTOR inhibitors, BRAF inhibitors and ipilimumab.After feasibility analysis in the first twenty patients, twenty more patients will be included in each of the five drug cohorts. Biopsies will be performed to determine possible immunohistochemical and histopathological changes in normal tissue, possible immunomodulatory changes as expressed by Tcell phenotyping and cytokine profiling and to compare tissue (phospho) proteomic and kinase activity profiles before and during therapy and also at the development of toxicity.The main objective of this pilot study is to determine the biological impact of treatment with targeted agents at the systemic and local tissue level in relation to toxicity.
Status | Terminated |
Enrollment | 8 |
Est. completion date | April 2017 |
Est. primary completion date | April 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Patients that will start palliative treatment with TKIs, mTOR inhibitors, ipilimumab, vemurafenib or EGFR inhibitors and therefore fulfill according to their attending physician all the usual criteria for receiving standard targeted therapy as monotherapy. 2. PT-INR/PTT < 1.5 x ULN. 3. Platelet count >/= 100 x 109/l Exclusion Criteria: 1. Concomitant use of anticoagulants 2. Previous colonic surgery in the last 3 months 3. History of inflammatory bowel disease, or other active gastrointestinal infection |
Country | Name | City | State |
---|---|---|---|
Netherlands | VU University Medical Center | Amsterdam |
Lead Sponsor | Collaborator |
---|---|
VU University Medical Center |
Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | histopathological and immunomodulatory changes | Biopsies of the areas most anticipated to be affected (skin, oral mucosa, colon mucosa) will be taken at the beginning and after 4 weeks of treatment. Specific attention will be directed in normal tissues at the percentage and types of inflammatory cells and cytokines. In addition, markers of proliferation and apoptosis will be evaluated. | 4 weeks | |
Primary | Kinase activity profiles | Kinase activity profiles will be measured according to standard methods as developed and modified in the laboratory of VUmc. PamChip will be applied to measure the signal intensity of both the pre- and on- treatment lysates, in the same experiment, to secure comparable conditions. The percentage inhibition is calculated by dividing the mean signal intensity of the on-treatment lysate by the mean signal intensity of the pre-treatment normal tissue lysates. | 4 weeks | |
Primary | Kinome wide and quantitative (phospho)proteomic profiles | Kinome wide and quantitative (phospho)proteomic profiles will be determined in normal tissue biopsies before and during treatment, for each patient. We anticipate that these profiles will reveal information on the effect of treatment on kinase abundances, phosphopeptide levels and on phosphorylation sites. Differences in levels of phosphopeptides and fold-change of phosphorylation sites will be quantified. We will try to correlate observed profile changes to toxicity development. | 4 weeks | |
Secondary | Based on the results of the primary aim, potential novel markers predictive for toxicity will be evaluated using the measurements as described under the primary subaims 1-3 | 4 weeks |