An open label phase I dose finding study of BI 853520 administered orally in a continuous dosing schedule in patients with various advanced or metastatic non-hematologic malignancies
- Conditions
- cancersolid tumours10027655
- Registration Number
- NL-OMON39828
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 45
- Patients with a confirmed diagnosis of advanced, measurable or evaluable, non-resectable and/or metastatic non-hematologic malignancy, which has shown to be progressive in the last 6 months as demonstrated by serial imaging;
- Patients who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to established treatment options;
-Tumour tissue must be available for the determination of E-cadherin expression (archived tissue or fresh biopsy);
- Recovery from reversible toxicities (alopecia excluded) of prior anti-cancer therapies (CTCAE grade < 2);
- Age >= 18 years;
- Written informed consent in accordance with International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) and local legislation;
- Eastern Cooperative Oncology Group (ECOG), performance score 0-1;
Additional inclusion criteria in the expansion phase:
- Patients must have measurable progressive disease within the last 6 months, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria;
- Patients must be willing to provide paired tumour biopsies for PD determination. Refer to section 5.6.3;
- Patients should fit into one of the categories described below:;
I. Metastatic adenocarcinoma of the pancreas;
Patients should have preferably received at least one line of systemic treatment for metastatic disease and preferably not more than 2 prior regimens for metastatic disease.;
II. Platinum-resistant ovarian carcinoma, defined as recurrence within 6 months after completion of prior platinum-based chemotherapy;
Patients should have preferably received no more than 5 previous lines of systemic treatment for metastatic disease;
III. Oesophageal carcinoma;
Patients with oesophageal carcinoma of adenocarcinoma- or squamous cell histology who have received preferably not more than 2 previous lines of systemic treatment for metastatic disease;
IV. Soft tissue sarcoma;
Patients should preferably have received no more than 2 previous lines of systemic treatment for metastatic disease.;
- Serious concomitant non-oncological disease/illness;- Pregnancy or breastfeeding;- Active/symptomatic brain metastases;- Second malignancy;- Women or men who are sexually active and unwilling to use a medically acceptable method of contraception ;- Treatment with cytotoxic anti-cancer-therapies or investigational drugs within four weeks of the first treatment with the study medication
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Determination of the MTD. It will be defined by the occurrence of dose-limiting<br /><br>toxicities (DLT) during the first treatment cycle of each patient in the dose<br /><br>finding phase.<br /><br>The MTD was determined as 200 mg. DLTs that occurred were fatigue (1) and<br /><br>proteinurea (2).</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Pharmacokinetic parameters of BI 853520 will be determined from plasma<br /><br>analyses after a single oral dose and after repeated dosing, at steady state:<br /><br>Cmax and Area Under the Curve<br /><br>• Pharmacodynamic assessment: pPTK2 modulation pre- and post treatment in skin<br /><br>or tumor<br /><br>• Exploratory evaluation of efficacy (e.g. objective response rate, disease<br /><br>control rate, duration of disease control, tumor shrinkage)</p><br>