BI 6727 (Volasertib) Monotherapy Phase I Trial in Japanese Patients With Advanced Solid Tumours

An Open-label Phase I Study of Once Every Three Weeks Intravenous Treatment With BI 6727 in Japanese Patients With Advanced Solid Tumours

This open-label phase I dose escalation trial, 1230.15, is the first trial with Volasertib in Japanese advanced cancer patients. The trial will investigate the maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy of this specific polo-like kinase 1 (Plk1) inhibitor in advanced cancer patients.

Inclusion criteria:

1. Patients with histologically or cytologically confirmed according to the discretion of the investigator

2. Patients who have advanced, non-resectable and/or metastatic solid tumours according to the discretion of the investigator

3. Patients who have failed conventional treatment, or for whom no therapy of proved efficacy exists, or who are not amenable to established forms of treatment according to the discretion of the investigator

4. Age >=20 years old at the time of informed consent

5. Written informed consent

6. Life expectancy of at least 12 weeks according to the discretion of the investigator

7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

8. Recovery to Common Terminology Criteria for Adverse Events (CTCAE) grade =1 of therapy-related toxicities from previous chemo-, hormonal-, immuno-, or radiotherapy (except alopecia and hyperpigmentation)

9. Adequate bone marrow, renal and hepatic function;

   • Neutrophil count: more than 1500/mm3
   • Platelet count: more than 100 000/mm3
   • Haemoglobin: more than 9.0 g/dL
   • Total bilirubin: less than 1.5 times the upper limit of normal (ULN)
   • Aspartate amino transferase (AST): less than 2.5 × ULN
   • Alanine amino transferase (ALT): less than 2.5 × ULN
   • Serum creatinine: less than 1.5 × ULN

10. Patients who can be hospitalised during the first course

Exclusion criteria:

1. Major surgery within 4 weeks prior to registration or the side effects/toxicities of such surgery that have not recovered to CTCAE grade =1

2. Known seropositivity to human immunodeficiency virus (HIV) antibody, hepatitis B antigen or hepatitis C antibody

3. Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid) requiring treatment during the trial (Patients are eligible if treated curatively and with no evidence of recurrence.)

4. Current symptomatic brain metastases or patients who require treatment of the brain metastases

5. Previous double cancers. Other tumours (except for non-invasive and/or non-melanomatous skin cancer, completely removed in situ carcinoma of the epithelium or mucosa) treated curatively and with no evidence of recurrence for at least 5 years prior to the initial study treatment will be eligible.

6. Known history of cardiac dysfunction;

   • Correction of QT intervals according to Fridericias formula (QTc) over 470 ms
   • History of unstable angina pectoris within 6 months or current unstable angina pectoris
   • History of myocardial infarction within 6 months
   • Arrhythmia currently required active therapy
   • Previous and current cardiac failure
   • History of other clinically significant cardiac diseases according to the discretion of the investigator

7. Pregnant or breastfeeding women

8. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices, vasectomised partner, or condoms) during the trial and for at least 6 months after the end of active therapy. Women who are sexually active are premenopausal female patients. Premenopausal female patient is defined as the patient who observed menses within 12 months except for an alternative medical cause. Women who underwent an operation for sterilisation is excluded for this criteria.

9. Treatment with other investigational drugs within the past 4 weeks before registration or concomitantly with this trial (except for present trial drug)

10. Chemo-, radio-, immuno-, or molecular-targeted therapy within the past 4 weeks before registration or concomitantly with this trial. This restriction does not apply to bisphosphonates.

11. Patients unable to comply with the protocol according to the discretion of the investigator or sub-investigators

12. Current alcohol abuse or drug abuse according to the discretion of the investigator

13. Patients who are inappropriate for this trial by the discretion of investigator or sub-investigators (e.g. uncontrolled diabetes mellitus, evidence of serious active infection, medically significant abnormal laboratory finding, etc.)