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

NCT01348347 | Completed Phase 1 Results

• 1 other identifier: 1230.15
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

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

  The following drug-related adverse events (AE) were defined as DLT; 1. Haematological toxicities: CTCAE(Common Terminology Criteria for Adverse Events) grade 4 neutropenia persisted for 7 or more days, CTCAE grade 4 thrombocytopenia or CTCAE grade 3 thrombocytopenia requiring blood transfusion. 2. Non-haematological toxicities: CTCAE grade ≥3 non-haematological toxicities. The following toxicity with neutropenia was defined as DLT.- CTCAE grade 3 febrile neutropenia persisted for over 2 days, Clinically significant laboratory abnormalities of CTCAE grade ≥3 persisted for over 3 days. The following laboratory abnormalities should be defined as DLT. - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): \>5.0 × ULN persisted for 7 days or longer - Creatinine: \>3.0 × upper limit of normal(ULN) (if the creatinine abnormality was observed even once) - Persistent electrolyte abnormality assessed by the investigator.

  21 days

• Maximum Tolerated Dose (MTD) of Volasertib

  Maximum tolerated dose (MTD) of volasertib was the highest dose tested at which DLT was developed in not more than 1 of 6 patients in the course 1.

  21 days

Secondary Outcomes (5)

• Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

  6 months

• Disease Control Rate According to RECIST v1.1

  6 months

• Cmax of Volasertib (BI 6727)

  Pharmacokinetic (PK) plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) of Volasertib (BI 6727)

  PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.

• Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 up to the Last Quantifiable Data Point (AUC0-tz) of Volasertib (BI 6727)

  PK plasma samples were taken at: 5 minutes predose, 1hour, 2hours (h), 3h, 4h, 8h, 24h, 48h, 72h, 96h, 168h and 336h of course1.

Study Arms (1)

Volasertib

EXPERIMENTAL

Patient to receive low, middle and high doses of Volasertib IV

Drug: Volasertib, low dose, d1q3w; Drug: Volasertib, middle dose, d1q3w; Drug: Volasertib, high dose, d1q3w

Interventions

Volasertib, low dose, d1q3w DRUG

Patient to receive low dose of Volasertib IV

Volasertib

Volasertib, middle dose, d1q3w DRUG

Patient to receive middle dose of Volasertib IV

Volasertib

Volasertib, high dose, d1q3w DRUG

Patient to receive high dose of Volasertib IV

Volasertib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed according to the discretion of the investigator
• Patients who have advanced, non-resectable and/or metastatic solid tumours according to the discretion of the investigator
• 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
• Age \>=20 years old at the time of informed consent
• Written informed consent
• Life expectancy of at least 12 weeks according to the discretion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• 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)
• 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

You may not qualify if:

• Major surgery within 4 weeks prior to registration or the side effects/toxicities of such surgery that have not recovered to CTCAE grade =1
• Known seropositivity to human immunodeficiency virus (HIV) antibody, hepatitis B antigen or hepatitis C antibody
• 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.)
• Current symptomatic brain metastases or patients who require treatment of the brain metastases
• 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.
• 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
• Pregnant or breastfeeding women
• 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.
• Treatment with other investigational drugs within the past 4 weeks before registration or concomitantly with this trial (except for present trial drug)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1230.15.001 National Cancer Center Hospital,

Chuo-ku, Tokyo, Japan

Location

Related Publications (1)

• Nokihara H, Yamada Y, Fujiwara Y, Yamamoto N, Wakui H, Nakamichi S, Kitazono S, Inoue K, Harada A, Taube T, Takeuchi Y, Tamura T. Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with advanced solid tumors. Invest New Drugs. 2016 Feb;34(1):66-74. doi: 10.1007/s10637-015-0300-0. Epub 2015 Dec 2.

  PMID: 26627079 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

BI 6727

Limitations and Caveats

250 mg dose of Volasertib was planned, as needed. However the 250 mg intermediate cohort had not been implemented in this trial.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 29, 2011
• First Posted: May 5, 2011
• Study Start: April 25, 2011
• Primary Completion: August 27, 2012
• Study Completion: May 15, 2014
• Last Updated: August 6, 2018
• Results First Posted: August 6, 2018

Record last verified: 2018-08

Locations

JP (1)