NeoplasmsPhase 1NCT01022853
Combination of BI6727 (Volasertib) and BIBF1120 in Solid Tumors
A Phase 1 study testing BI 6727 and BIBF 1120 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- BI 6727 and BIBF 1120
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesItaly
- Study dates
- Dec 2009to Feb 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Age > or = 18 years
- European Cooperative Oncology Group performance status < or = 2
- Written informed consent in accordance with International Conference on Harmonization -Good Clinical Practice (ICH-GCP) and local legislation
- Recovery from Common Terminology Criteria for Adverse Events grade 2-4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapy (except alopecia)
Who cannot join
- Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the trial
- Known hypersensitivity to the trial drugs or their excipients
- 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
- 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
- Active infectious disease infection or HIV I/II
- Other malignancy currently requiring another anti-cancer therapy
Show all 25Show fewer
- Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
- Known inherited predisposition to bleeding or thrombosis
- Radiographic evidence of cavitary or necrotic tumours
- History of clinically significant haemoptysis within the past 3 months
- Centrally located tumours with radiographic evidence (Computed Tomography or Magnetic Resonance Imaging) of local invasion of major blood vessels
- Absolute Neutrophil Count (ANC) less than 1.5 x 1000000000/L
- Platelets Count (PLT) less than 100 x 1000000000/L
- Total bilirubin > upper limit of normal (ULN)
- Alaninaminotransferase (ALT) and/or Aspartateaminotransferase (AST) >= 1.5 x ULN (in case of liver metastases: ALT and AST >= 2.5 x ULN)
- Serum creatinine > 1.5 mg/dl
- 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
- Known history of clinically relevant QT prolongation (e.g. long QT syndrome)
- History of severe haemorrhagic or thromboembolic event in the past 6 months (excluding central venous catheter thrombosis and peripheral deep vein thrombosis)
- 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)
- Active alcohol or drug abuse
- Women and men who are sexually active and unwilling to use a medically acceptable method of contraception during the trial
- Pregnancy or breast-feeding
- Patients unable to comply with the protocol
- Uncontrolled hypertension
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
1230.7.39002 Boehringer Ingelheim Investigational Site
Ancona
1230.7.39001 Boehringer Ingelheim Investigational Site
Milan
About this study
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
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.
- Conditions
- Neoplasms
- Being tested
- BI 6727, BIBF 1120
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 6727Drug
intravenous each 21 days
BIBF 1120Drug
oral continuously
| Study group | Role | What they receive |
|---|---|---|
| BIBF 1120 and BI 6727 | Experimental | Finding Maximum Tolerated Dose of BI 6727 in combination with BIBF 1120 Receives: Drug: BI 6727; Drug: BIBF 1120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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
- Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or
- CTCAE grade 4 thrombocytopenia
Measured: 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.
Measured: 28 days
Secondary outcomes (13)
Number of Participants With Drug Related Adverse Events
Number of participants with investigator-defined drug related adverse events.
Measured: 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:
- Drug-related CTCAE grade 3 or 4 non-haematological toxicity (except untreated vomiting, untreated nausea, or untreated diarrhoea) or
- Drug-related CTCAE grade 4 neutropenia for 7 or more days and/or complicated by infection or
- CTCAE grade 4 thrombocytopenia
Measured: 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.
Measured: 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
CL of Volasertib
Total plasma Clearance (CL) of Volasertib in Cycle 1.
Measured: 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
Vss of Volasertib
Volume of distribution at steady state (Vss) of Volasertib in Cycle 1.
Measured: 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
Cmax of Nintedanib
Maximum measured concentration (Cmax) of Nintedanib in Cycle 1.
400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.
Measured: 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
AUC(0-6h) of Nintedanib
Area under the concentration-time curve (AUC) of Nintedanib over the time interval 0 to 6 hours in Cycle 1.
400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.
Measured: 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
Tmax of Nintedanib
Time from dosing to the maximum measured concentration, Cmax, of Nintedanib (tmax) in Cycle 1.
400 mg Volasertib + 200 mg Nintedanib group is not displayed due to data only being available for one patient.
Measured: 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
Number of Patients With Best Overall Response
Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as the best overall response (complete response, partial response, stable disease, progressive disease or not evaluable) since the start of treatment.
Measured: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Number of Patients With Objective Response (OR)
Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR) as best response throughout the study.
Measured: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Number of Patients With Disease Control
Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Disease control is defined as complete response (CR), partial response (PR) or stable disease (SD) as best response throughout the study.
Measured: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Duration of Disease Control
Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control.
Measured: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Progression Free Survival (PFS)
PFS is defined as the time from start of treatment with study medication to tumour progression or death whichever occurs first. Tumour response was to be documented using appropriate techniques such as magnetic resonance imaging (MRI) or computer tomography (CT).
Measured: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01022853
- Sponsor's protocol ID
- 1230.7
- Other IDs
- 2008-008304-41, 2008
- Status last verified
- Oct 2017
- First submitted
- 26 Nov 2009
- Last updated
- 30 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01022853
- Acronym / sponsor ID
- 1230.7
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 1 Dec 2009 (estimated)
- Results
- Posted 30 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BIBF 1120 and BI 6727 | Experimental | Drug: BI 6727, Drug: BIBF 1120Finding Maximum Tolerated Dose of BI 6727 in combination with BIBF 1120 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- Age > or = 18 years
- European Cooperative Oncology Group performance status < or = 2
- Written informed consent in accordance with International Conference on Harmonization -Good Clinical Practice (ICH-GCP) and local legislation
- Recovery from Common Terminology Criteria for Adverse Events grade 2-4 therapy-related toxicities from previous systemic anti-cancer therapies or radiotherapy (except alopecia)
Key exclusion criteria (25 listed)
- Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the trial
- Known hypersensitivity to the trial drugs or their excipients
- 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
- 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
- Active infectious disease infection or HIV I/II
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BI 6727intravenous each 21 days | Drug | BIBF 1120 and BI 6727 |
| BIBF 1120oral continuously | Drug | BIBF 1120 and BI 6727 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD).
Time frame: 28 days
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
Maximum Tolerated Dose (MTD) of Volasertib in Combination With Nintedanib
Time frame: 28 days
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.
13 secondary outcomes
Number of Participants With 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
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
Time frame: 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
CL of Volasertib
Time frame: 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
Vss of Volasertib
Time frame: 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
Cmax of Nintedanib
Time frame: 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
AUC(0-6h) of Nintedanib
Time frame: 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
Tmax of Nintedanib
Time frame: 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
Number of Patients With Best Overall Response
Time frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Number of Patients With Objective Response (OR)
Time frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Number of Patients With Disease Control
Time frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Duration of Disease Control
Time frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Progression Free Survival (PFS)
Time frame: Tumor assessment was performed at screening and every 2nd course until earliest time of progression, death or end of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BI 6727 and BIBF 1120 in people with Neoplasms, run by Boehringer Ingelheim at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD). (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2018.