NeoplasmsPhase 1NCT01206816

An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 (Volasertib)in Combination With Oral BIBW 2992 (Afatinib) in Patients With Advanced Solid Tumours

A Phase 1 study testing BI 6727 + BIBW 2992 in people with Neoplasms, run by Boehringer Ingelheim at 3 sites in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: BI 6727 + BIBW 2992
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 57 participants
Where: 3 sitesBelgium
Study dates: 4 Oct 2010to 15 Nov 2012
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 histologically or cytologically confirmed diagnosis of advanced, non resectable and/or metastatic, relapsed or refractory solid tumours not amenable to standard therapy and for whom no therapy of proven efficacy exists
Eastern Cooperative Oncology Group performance score 0 - 2
Recovery from clinically significant toxicities from previous systemic anti-cancer therapies or radiotherapy

Who cannot join

Serious illness, concomitant non-oncological disease or mental problem considered by the investigator to be incompatible with participation to the trial
Known hypersensitivity to the trial drugs or their excipients
Treatment with any other investigational drug or active participation in any other interventional trial within 28 days before first administration of trial drug(s) or concomitantly with this trial
Major surgery or radiotherapy within 28 days before start of therapy or concomitantly with this trial
Systemic anti-cancer therapy within 28 days before start of therapy or concomitantly with this trial
Requirements for treatment with any of the prohibited concomitant medications

Show all 18Show fewer

Active infectious disease or known HIV I/II infection
Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea
Active brain metastases
History or presence of cardiovascular abnormalities deemed clinically relevant by the investigator
Cardial left ventricular function with resting ejection fraction < 50%
Inadequate hepatic, renal and haematologic organ function
QT prolongation deemed clinically relevant by the investigator
Active alcohol or drug abuse
Women of childbearing potential and men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial and 28 days thereafter
Pregnancy or breast-feeding
Patients unable to comply with the protocol
Patients with known pre-existing interstitial lung disease

Trial locations and contacts

3 sites in 1 country.

Belgium3 sites

1230.20.32001 Boehringer Ingelheim Investigational Site
Brussels
1230.20.32003 Boehringer Ingelheim Investigational Site
Edegem
1230.20.32002 Boehringer Ingelheim Investigational Site
Ghent

Other trials in Belgium

About this study

Official title: An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBW 2992 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 the combination of BI 6727 with BIBW 2992, in patients with advanced or metastatic solid tumours. Dosages of both BI 6727 and BIBW 2992 will be varied to establish the MTD of the combination. Two combination treatment schedules will be tested, the MTD of each combination will be determined.

Secondary objectives are the exploration of pharmacokinetics, overall safety and preliminary efficacy.

Conditions: Neoplasms
Being tested: BI 6727 + BIBW 2992
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BI 6727 + BIBW 2992Drug
BI 6727 administered i.v. every 21 days + BIBW 2992 given orally once a day

Study groups in NCT01206816
Study group	Role	What they receive
two experimental arms	Experimental	patients receive increasing doses of BI 6727 in combination with increasing doses of BIBW 2992 Receives: Drug: BI 6727 + BIBW 2992

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicities (DLT)
MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, <500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever >38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.
Measured: 22 Days
Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.
Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The "3 + 3 design with de-escalation" for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days.
Measured: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)

Secondary outcomes (4)

Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0
Number of patients with investigator defined drug-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v 3.0
Measured: After the first drug administration until 28 days after the last drug administration, up to 413 days.
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 Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
Measured: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
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 complete response, partial response, stable disease, progressive disease or not evaluable.
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Measured: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Number of Patients With 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.
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Measured: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Oct 201015 Nov 2012

First posted22 Sep 2010 (estimated)
Study start4 Oct 2010
Primary completion15 Nov 2012
Study completion15 Nov 2012

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.
Publications (1)Papers the sponsor has linked to this study.
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: Non-randomised
Masking: None (open label)
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01206816
Sponsor's protocol ID: 1230.20
Other IDs: 2010-019437-97
Status last verified: Aug 2018
First submitted: 21 Sep 2010
Last updated: 1 Feb 2019
Results posted: Yes, on ClinicalTrials.gov

Publications

Machiels JP, Peeters M, Herremans C, Surmont V, Specenier P, De Smet M, Pilz K, Strelkowa N, Liu D, Rottey S. A phase I study of volasertib combined with afatinib, in advanced solid tumors. Cancer Chemother Pharmacol. 2015 Oct;76(4):843-51. doi: 10.1007/s00280-015-2860-2. Epub 2015 Sep 8.
PubMed 26349473

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2019. 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 BIBW 2992 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
ClinicalTrials.gov ID: NCT01206816
Acronym / sponsor ID: 1230.20
Conditions: Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 57 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 4 Oct 2010 (actual)
Primary completion: 15 Nov 2012 (actual)
Study completion: 15 Nov 2012 (actual)
First posted: 22 Sep 2010 (estimated)
Results: Posted 1 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Secondary objectives are the exploration of pharmacokinetics, overall safety and preliminary efficacy.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
two experimental arms	Experimental	Drug: BI 6727 + BIBW 2992patients receive increasing doses of BI 6727 in combination with increasing doses of BIBW 2992

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and/or metastatic, relapsed or refractory solid tumours not amenable to standard therapy and for whom no therapy of proven efficacy exists
Eastern Cooperative Oncology Group performance score 0 - 2
Recovery from clinically significant toxicities from previous systemic anti-cancer therapies or radiotherapy

Key exclusion criteria (18 listed)

Serious illness, concomitant non-oncological disease or mental problem considered by the investigator to be incompatible with participation to the trial
Known hypersensitivity to the trial drugs or their excipients
Treatment with any other investigational drug or active participation in any other interventional trial within 28 days before first administration of trial drug(s) or concomitantly with this trial
Major surgery or radiotherapy within 28 days before start of therapy or concomitantly with this trial
Systemic anti-cancer therapy within 28 days before start of therapy or concomitantly with this trial

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 6727 + BIBW 2992BI 6727 administered i.v. every 21 days + BIBW 2992 given orally once a day	Drug	two experimental arms

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLT)
Time frame: 22 Days
MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, <500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever >38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.
Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.
Time frame: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)
Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The "3 + 3 design with de-escalation" for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days.

4 secondary outcomes

Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0
Time frame: After the first drug administration until 28 days after the last drug administration, up to 413 days.
Number of Patients With Objective Response (OR)
Time frame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Number of Patients With Best Overall Response.
Time frame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Number of Patients With Disease Control
Time frame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).

Results and safety

Results posted to the registry on 1 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Volasertib150 mg+Afatinib 30 mg (Schedule A)	3	0
Volasertib 225 mg+Afatinib 30 mg (Schedule A)	3	0
Volasertib 300 mg+Afatinib 30 mg (Schedule A)	20	0
Volasertib 300 mg+Afatinib 40 mg (Schedule A)	3	0
Volasertib 300 mg+Afatinib 50 mg (Schedule B)	3	0
Volasertib 300 mg+Afatinib 70 mg (Schedule B)	19	0
Volasertib 300 mg+Afatinib 90 mg (Schedule B)	6	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLT)

Time frame: 22 Days. Number. Unit: participants

Measure	Volasertib150 mg+Afatinib 30 mg (Schedule A) n = 3	Volasertib 225 mg+Afatinib 30 mg (Schedule A) n = 3	Volasertib 300 mg+Afatinib 30 mg (Schedule A) n = 20	Volasertib 300 mg+Afatinib 40 mg (Schedule A) n = 3	Volasertib 300 mg+Afatinib 50 mg (Schedule B) n = 3	Volasertib 300 mg+Afatinib 70 mg (Schedule B) n = 19	Volasertib 300 mg+Afatinib 90 mg (Schedule B) n = 6
Value	0	0	3	2	0	5	2

Population analysed: Treated Set (TS)

Primary outcome: Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.

Time frame: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days). Number. Unit: mg

Measure	Volasertib in Combination With Afatinib (Schedule A) n = 29	Volasertib in Combination With Afatinib (Schedule B) n = 28
Volasertib	300	300
Afatinib	30	70

Population analysed: Treated Set (TS)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: After the first drug administration until 28 days after the last drug administration, upto 413 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Volasertib150 mg+Afatinib 30 mg (Schedule A)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Volasertib 225 mg+Afatinib 30 mg (Schedule A)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Volasertib 300 mg+Afatinib 30 mg (Schedule A)	11 of 20 (55%)	18 of 20 (90%)	Not reported
Volasertib 300 mg+Afatinib 40 mg (Schedule A)	2 of 3 (66.7%)	3 of 3 (100%)	Not reported
Volasertib 300 mg+Afatinib 50 mg (Schedule B)	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Volasertib 300 mg+Afatinib 70 mg (Schedule B)	12 of 19 (63.2%)	19 of 19 (100%)	Not reported
Volasertib 300 mg+Afatinib 90 mg (Schedule B)	3 of 6 (50%)	6 of 6 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26349473Machiels JP, Peeters M, Herremans C, Surmont V, Specenier P, De Smet M, Pilz K, Strelkowa N, Liu D, Rottey S. A phase I study of volasertib combined with afatinib, in advanced solid tumors. Cancer Chemother Pharmacol. 2015 Oct;76(4):843-51. doi: 10.1007/s00280-015-2860-2. Epub 2015 Sep 8.
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

3 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 + BIBW 2992 in people with Neoplasms, run by Boehringer Ingelheim at 3 sites in Belgium.

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 3 inclusion and 18 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 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Belgium. 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 1 Feb 2019). 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 (DLT) (time frame: 22 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?

On the ClinicalTrials.gov record for NCT01206816, which also lists 1 linked publication.

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 1 Feb 2019.