A Study of BI 853520 in Patients With Various Types of Advanced or Metastatic Cancer

NCT01335269 | Completed Phase 1

• 2 other identifiers: 1300.22010-024609-10
• Study Type: interventional
• Target: 96
• Locations: 2 countries
• Sites: 5

Brief Summary

The primary objective of this trial is to determine the safety and tolerability of BI 853520 monotherapy by defining the maximum tolerated dose (MTD) and recommending the dose for further trials in the development of this compound. Secondary objectives are

• determination of the pharmacokinetic (PK) profile;
• exploratory pharmacodynamic analysis; and
• collection of preliminary data on anti-tumour efficacy.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Determination of the MTD. It will be defined by the occurrence of dose-limiting toxicities (DLT) during the first treatment cycle of each patient in the dose finding phase

  After the first 28 days of treatment

Secondary Outcomes (9)

• Cmax (maximum measured concentration of the analyte in plasma) after first dose

  up to 48 hours

• AUCt,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t after administration of the first dose)

  up to 48 hours

• Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t) after the last dose in cycle 1

  up to 24 hours

• AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) after the last dose in cycle 1

  up to 24 hours

• Disease control rate (CR or PR or SD per RECIST v1.1) )

  up to 39 months

Study Arms (1)

Treatment arm

EXPERIMENTAL

BI 853520 once daily in a dose escalation schedule

Drug: BI 853520

Interventions

BI 853520 DRUG

BI 853520 once daily in a dose escalation schedule

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a confirmed diagnosis of advanced, measurable or evaluable, nonresectable 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
• Life expectancy = 3 months
• Written informed consent in accordance with International Conference on Harmonisation/Good Clinical Practice (ICH/GCP) and local legislation, including consent for PK samples, for using an archived tumour sample for determination of Ecadherin status, for reviewing previous tumour scans (and for providing skin biopsies, in patients in dose finding phase enrolled before protocol amendment 03)
• Eastern Cooperative Oncology Group (ECOG), R01-0787) performance score 0-1
• Patients must have measurable progressive disease within the last 6 months, according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (version 1.1, R09-0262)
• deleted
• 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 received preferably 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.

You may not qualify if:

• Serious concomitant non-oncological disease/illness
• Active/symptomatic brain metastases
• Second malignancy
• Pregnancy or breastfeeding
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (5)

1300.2.1002 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1300.2.1001 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1300.2.31003 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

Location

1300.2.31001 Boehringer Ingelheim Investigational Site

Rotterdam, Netherlands

Location

1300.2.31002 Boehringer Ingelheim Investigational Site

Utrecht, Netherlands

Location

Related Publications (3)

• Fard D, Giraudo E, Tamagnone L. Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer. Trends Mol Med. 2023 Oct;29(10):817-829. doi: 10.1016/j.molmed.2023.07.009. Epub 2023 Aug 17.

  PMID: 37598000 DERIVED

• de Jonge MJA, Steeghs N, Lolkema MP, Hotte SJ, Hirte HW, van der Biessen DAJ, Abdul Razak AR, De Vos FYFL, Verheijen RB, Schnell D, Pronk LC, Jansen M, Siu LL. Phase I Study of BI 853520, an Inhibitor of Focal Adhesion Kinase, in Patients with Advanced or Metastatic Nonhematologic Malignancies. Target Oncol. 2019 Feb;14(1):43-55. doi: 10.1007/s11523-018-00617-1.

  PMID: 30756308 DERIVED

• Verheijen RB, van der Biessen DAJ, Hotte SJ, Siu LL, Spreafico A, de Jonge MJA, Pronk LC, De Vos FYFL, Schnell D, Hirte HW, Steeghs N, Lolkema MP. Randomized, Open-Label, Crossover Studies Evaluating the Effect of Food and Liquid Formulation on the Pharmacokinetics of the Novel Focal Adhesion Kinase (FAK) Inhibitor BI 853520. Target Oncol. 2019 Feb;14(1):67-74. doi: 10.1007/s11523-018-00618-0.

  PMID: 30742245 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 14, 2011
• Study Start: July 1, 2011
• Primary Completion: September 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 9, 2015

Record last verified: 2015-12

Locations

NL (3); CA (2)