Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors

Boehringer Ingelheim30 enrolled

Overview

The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD) in terms of safety and tolerability of BI 6727 in combination with fixed dose BIBF 1120, in patients with advanced or metastatic solid tumours.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

BI 6727DRUG

intravenous each 21 days

BIBF 1120DRUG

oral continuously

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Patients with confirmed diagnosis of advanced, non resectable and/or metastatic solid tumours, who have failed conventional treatment, and for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment 2. Age \> or = 18 years 3. European Cooperative Oncology Group performance status \< or = 2 4. Written informed consent in accordance with International Conference on Harmonization -Good Clinical Practice (ICH-GCP) and local legislation 5. Recovery from Common Terminology Criteria for Adverse Events grade 2-4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapy (except alopecia) Exclusion criteria: 1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the trial 2. Known hypersensitivity to the trial drugs or their excipients 3. Treatment with any other investigational drug or participation in any other interventional trial within 28 days before first administration of trial drug (BIBF 1120) or concomitantly with this trial 4. Systemic anti-cancer therapy or radiotherapy within 28 days before start of therapy or concomitantly with this trial. The restriction does not apply to steroids and bisphosphonates 5. Active infectious disease infection or HIV I/II 6. Other malignancy currently requiring another anti-cancer therapy 7. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months 8. Known inherited predisposition to bleeding or thrombosis 9. Radiographic evidence of cavitary or necrotic tumours 10. History of clinically significant haemoptysis within the past 3 months 11. Centrally located tumours with radiographic evidence (Computed Tomography or Magnetic Resonance Imaging) of local invasion of major blood vessels 12. Absolute Neutrophil Count (ANC) less than 1.5 x 1000000000/L 13. Platelets Count (PLT) less than 100 x 1000000000/L 14. Total bilirubin \> upper limit of normal (ULN) 15. Alaninaminotransferase (ALT) and/or Aspartateaminotransferase (AST) \>= 1.5 x ULN (in case of liver metastases: ALT and AST \>= 2.5 x ULN) 16. Serum creatinine \> 1.5 mg/dl 17. Major injuries and/or surgery or bone fracture within 28 days before first administration of trial drug (BIBF 1120), or planned surgical procedures during the trial period 18. Known history of clinically relevant QT prolongation (e.g. long QT syndrome) 19. History of severe haemorrhagic or thromboembolic event in the past 6 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis) 20. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid \< or = 325mg per day) 21. Active alcohol or drug abuse 22. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception during the trial 23. Pregnancy or breast-feeding 24. Patients unable to comply with the protocol 25. Uncontrolled hypertension

Locations (2)

1230.7.39002 Boehringer Ingelheim Investigational Site

Ancona, Italy

1230.7.39001 Boehringer Ingelheim Investigational Site

Milan, Italy

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD).

DLT was defined as: 1. Drug-related CTCAE (Common Terminology Criteria for Adverse Events) grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or 2. Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or 3. CTCAE grade 4 thrombocytopenia

Time frame: 28 days

Maximum Tolerated Dose (MTD) of Volasertib in Combination With Nintedanib

The MTD was determined using a 3+3 design with de-escalation. The MTD was defined as the highest dose level at which maximal 1 out of 6 patients experienced DLT in the first course of the escalation nd de-escalation phase. However, all DLT's occurring in the trial were considered for selection of the recommended dose for further development.

Time frame: 28 days

Secondary Outcomes

Number of Participants With Drug Related Adverse Events

Number of participants with investigator-defined drug related adverse events.

Time frame: From first study drug administration until 28 days after the last administration of any study medication, up to 485 days

Number of Participants With Dose Limiting Toxicities

Number of participants with dose limiting toxicities (DLTs). DLT was defined as: 1. Drug-related CTCAE grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or 2. Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or 3. CTCAE grade 4 thrombocytopenia

Time frame: From first study drug administration until 28 days after the last administration of any study medication, up to 485 days

Cmax of Volasertib

Maximum measured concentration (Cmax) in plasma of Volasertib in Cycle 1.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.