Clinical trial NCT00969761: BI 6727 (Volasertib) in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumour
Official title: A Phase I Dose Escalation Trial of BI 6727 in Combination With Cisplatin or Carboplatin in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-09-01
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to identify the maximum tolerated dose (MTD) of BI 6727 therapy in terms of drug-related adverse events when combined with a platinum therapy (cisplatin or carboplatin).

Secondary objectives are the collection of overall safety and antitumour efficacy data and the determination of the pharmacokinetic profile of BI 6727 combination treatment with cisplatin and carboplatin.


Eligibility criteria: Inclusion criteria:

1. Patients with confirmed diagnosis of advanced, non resectable and / or metastatic solid tumours, who have failed conventional treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to established forms of treatment
2. Indication for a treatment with platinum therapy as judged by the investigator
3. Age 18 years or older
4. Written informed consent consistent with ICH-GCP and local legislation
5. ECOG performance score lower or equal 2
6. Recovery from CTCAE Grade 2 - 4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapies (except alopecia grade 2)

Exclusion criteria:

1. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
2. Pregnancy or breastfeeding
3. Active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV I/II
4. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
5. Second malignancy currently requiring another anti-cancer therapy
6. ANC less than 1500 / mm3
7. Platelet count less than 100 000 / mm3
8. Bilirubin greater than 1.5 mg / dl (\> 26 micromol / L, SI unit equivalent) (except Gilbert's syndrome)
9. Aspartate amino transferase (AST) and / or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal)
10. Serum creatinine greater than 1.5 mg / dl (\> 132 micromol / L, SI unit equivalent) or creatinine clearance \<70ml/min (as calculated according to Cockcroft-Gault formula for GFR estimate)
11. Known history of relevant QT-prolongation, e.g. long QT-syndrome
12. Pre-existing clinically relevant hearing loss
13. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
14. Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks before start of therapy or concomitantly with this trial
15. Systemic anti-cancer therapy or radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to steroids and bisphosphonates.
16. Patients unable to comply with the protocol
17. Active alcohol or drug abuse

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 3 weeks
Secondary outcomes:
measure: Percentage of Participants With Dose Limiting Toxicities
timeFrame: 3 weeks
measure: Objective Response Rate
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Duration of Objective Response
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Best Overall Response
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Disease Control Rate
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Duration of Disease Control
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Progression-free Survival
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Incidence and Intensity of Adverse Events According to CTCAE Version 3.0
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Percentage of Participants With Serious Adverse Events
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Percentage of Participants With Significant Adverse Events
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Total Plasma Clearance After Intravascular Administration (CL)
timeFrame: 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion
measure: Apparent Volume of Distribution at Steady State Following Intravascular Administration (Vss)
timeFrame: 1 hour (h) 35 minutes (min) before start of volasertib infusion and 1h, 2h, 8h, 24h, 48h, 168h and 336h after start of volasertib infusion
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Change From Baseline in Neutrophils
timeFrame: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Change From Baseline in Platelets
timeFrame: Baseline and from first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Neutrophils
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Frequency of Participants (%) With Possible Clinically Significant Abnormalities for Platelets
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Last Value on Treatment
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Last Value on Treatment
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Platelets Based on Worst Value on Treatment
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Frequency of Participants With Transitions Relative to the Baseline CTC Grade for Neutrophils Based on Worst Value on Treatment
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Worst CTCAE Grade on Treatment for Platelets
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
measure: Worst CTCAE Grade on Treatment for Neutrophils
timeFrame: From first intake of trial drug to last intake of trial drug plus 21 days, up to 441 days
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: 1230.6.3201 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1230.6.3202 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Awada A, Dumez H, Aftimos PG, Costermans J, Bartholomeus S, Forceville K, Berghmans T, Meeus MA, Cescutti J, Munzert G, Pilz K, Liu D, Schoffski P. Phase I trial of volasertib, a Polo-like kinase inhibitor, plus platinum agents in solid tumors: safety, pharmacokinetics and activity. Invest New Drugs. 2015 Jun;33(3):611-20. doi: 10.1007/s10637-015-0223-9. Epub 2015 Mar 22.