Clinical trial NCT01022853: Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors
Official title: An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBF 1120 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-12-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD).
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD) of Volasertib in Combination With Nintedanib
timeFrame: 28 days
Secondary outcomes:
measure: Number of Participants With Drug Related Adverse Events
timeFrame: From first study drug administration until 28 days after the last administration of any study medication, up to 485 days
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: From first study drug administration until 28 days after the last administration of any study medication, up to 485 days
measure: Cmax of Volasertib
timeFrame: 0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion
measure: CL of Volasertib
timeFrame: 0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion
measure: Vss of Volasertib
timeFrame: 0:05 h before start of Volasertib infusion and 1:00, 2:00, 3:00, 4:00, 8:00 and 24 h after start of Volasertib infusion
measure: Cmax of Nintedanib
timeFrame: 5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9
measure: AUC(0-6h) of Nintedanib
timeFrame: 5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9
measure: Tmax of Nintedanib
timeFrame: 5 min before Nintedanib administration in the morning and 1:00, 2:00, 3:00, 4:00, 6:00 h after administration on Day 9
measure: Number of Patients With Best Overall Response
timeFrame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
measure: Number of Patients With Objective Response (OR)
timeFrame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
measure: Number of Patients With Disease Control
timeFrame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
measure: Duration of Disease Control
timeFrame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
measure: Progression Free Survival (PFS)
timeFrame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: 1230.7.39002 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 1230.7.39001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: