NeoplasmsPhase 1NCT01324830

Monotherapy Dose Finding With BI 847325 in Solid Tumours

A Phase 1 study testing day 1 to day 5 and day 1 to day 14 in people with Neoplasms, run by Boehringer Ingelheim at 2 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

The aim of the Phase Ia (dose escalation) part of this trial is to assess the maximum tolerated dose (MTD) of BI 847325 administered at escalating doses in 2 treatment arms. In the Phase Ib expansion part of the trial, the aim is to further evaluate the safety profile of BI 847325 at the recommended dose and schedule… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: day 1 to day 5 and day 1 to day 14
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 69 participants
Where: 2 sitesBelgium
Study dates: 15 Apr 2011to 10 Oct 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 a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic solid tumour, and who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to standard therapies.
Age 18 years and older
Written informed consent consistent with International conference on harmonization - Good clinical practice (ICH-GCP) and local legislation
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
Recovery of therapy-related toxicities from previous anti-tumour therapies to Common Terminology Criteria for Adverse Events (CTCAE) = grade 1 (with the exception of alopecia).
Written informed consent to the use of archival tumour sample for determination of the BRAF/Tat sarcoma viral oncogene homolog (RAS) mutational status.

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Life expectancy of at least 12 weeks.
In escalation phase, when pharmacokinetic (PK) close to predicted Cmax or when signs of progressive disease (PD) modulation present, optional tumour biopsies (at same timepoints as in expansion phase) for the patients who consented to it.
In addition, all patients included in the expansion phase (part Ib) must:
have been diagnosed with one of the following tumours: melanoma, colorectal carcinoma, Non Small Cell Lung Cancer (NSCLC) or exocrine pancreas adenocarcinoma, and have been shown on their archival tumour sample to have KRAS or BRAF mutation.
have a measurable disease.
have documented/proven progressive disease within the last 6 months, according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria
11. have a tumour lesion accessible for biopsies (pre- and post-treatment): this is mandatory for patients with colorectal carcinoma or melanoma, optional for patients with NSCLC or exocrine pancreas adenocarcinoma.

Who cannot join

Inability to swallow tablets.
Additional other serious illness , concomitant non-oncological disease (e.g. active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial.
Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days.
Second malignancy currently requiring another anti-cancer therapy.
Absolute neutrophil count less than 1500/mm3.
Platelet count less than 100 000/mm3.

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Bilirubin greater than 1.5 mg/dL (>26 µmol/L, Système international (SI) unit equivalent) (except known Gilbert's syndrome).
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).
Serum creatinine greater than 1.5 mg/dL (>132 µmol/L, SI unit equivalent).
Previous episode of QT prolongation due to a medication which, as a result of it, had to be discontinued; or long QT syndrome; or corrected QT interval (QTc) with Fridericia's correction >480 msec on screening ECG.
Pregnancy or breastfeeding.
Women or men who are sexually active and unwilling to use a medically acceptable method of contraception.
Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks before start of therapy or concomitant with this trial.
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 Luteinizing hormone-releasing hormone (LHRH) agonists, steroids and bisphosphonates.
Patients unable to comply with the protocol.
Active alcohol or drug abuse.
history or presence of cardiovascular abnormalities deemed clinically relevant by the investigator. Myocardial infarction within 6 months prior to study.
Cardiac left ventricular ejection fraction <50% or less than institutional lower limit of normal by Multiple Gated Acquisition scan (MUGA) or echocardiography

Trial locations and contacts

2 sites in 1 country.

Belgium2 sites

1287.1.3201 Boehringer Ingelheim Investigational Site
Brussels
1287.1.3202 Boehringer Ingelheim Investigational Site
Leuven

Other trials in Belgium

About this study

Official title: An Open Label Phase Ia/Ib Study of Two Dosing Schedules of BI 847325, Orally Administered Once a Day in Patients With Advanced Solid Tumours, With Repeated Cyclic Administration in Patients With Clinical Benefit

Conditions: Neoplasms
Being tested: day 1 to day 5, day 1 to day 14
Medical subject headings: Neoplasms

What participants receive

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

day 1 to day 5Drug
low to high dose
day 1 to day 14Drug
low to high dose

Study groups in NCT01324830
Study group	Role	What they receive
arm A	Experimental	14 days once a day oral intake of BI 847325 followed by 7 days break in 3-week cycles Receives: Drug: day 1 to day 14
arm B	Experimental	5 days once daily oral intake of BI 847325 followed by 2 days break, repeated every week Receives: Drug: day 1 to day 5

What is being measured

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

Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study
Occurrence of dose limiting toxicity (DLT) during the first treatment cycle for the treatment Schedules A and B.
Some patients excluded from Treated Set (TS) as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Measured: 3 weeks

Secondary outcomes (3)

Best Overall Response
Best overall response was the best response a patient experienced during their time on study from the start of treatment until: disease progression, the last evaluable assessment in the absence of progression, or the start of subsequent anti-cancer therapy. Death was not considered as progressive disease when determining best overall response; patients who died prior to an evaluable imaging assessment were reported as not evaluable. Some patients were excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Measured: From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013
Objective Response
Objective response was a best overall response of complete or partial response, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment.
Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Measured: From the start of treatment and the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
Disease Control
Disease control was a best overall response of complete response, partial response or stable disease, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment. Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Measured: From the start of treatment to the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.

Timeline

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

15 Apr 201110 Oct 2013

First posted29 Mar 2011 (estimated)
Study start15 Apr 2011
Primary completion6 Jun 2013
Study completion10 Oct 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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01324830
Sponsor's protocol ID: 1287.1
Other IDs: 2010-023832-18
Status last verified: Jun 2018
First submitted: 23 Mar 2011
Last updated: 21 Dec 2018
Results posted: Yes, on ClinicalTrials.gov

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?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label Phase Ia/Ib Study of Two Dosing Schedules of BI 847325, Orally Administered Once a Day in Patients With Advanced Solid Tumours, With Repeated Cyclic Administration in Patients With Clinical Benefit
ClinicalTrials.gov ID: NCT01324830
Acronym / sponsor ID: 1287.1
Conditions: Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 69 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 15 Apr 2011 (actual)
Primary completion: 6 Jun 2013 (actual)
Study completion: 10 Oct 2013 (actual)
First posted: 29 Mar 2011 (estimated)
Results: Posted 21 Dec 2018

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
arm A	Experimental	Drug: day 1 to day 1414 days once a day oral intake of BI 847325 followed by 7 days break in 3-week cycles
arm B	Experimental	Drug: day 1 to day 55 days once daily oral intake of BI 847325 followed by 2 days break, repeated every week

Who may qualify

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

Key inclusion criteria (13 listed)

Patients with a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic solid tumour, and who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to standard therapies.
Age 18 years and older
Written informed consent consistent with International conference on harmonization - Good clinical practice (ICH-GCP) and local legislation
Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
Recovery of therapy-related toxicities from previous anti-tumour therapies to Common Terminology Criteria for Adverse Events (CTCAE) = grade 1 (with the exception of alopecia).

Key exclusion criteria (18 listed)

Inability to swallow tablets.
Additional other serious illness , concomitant non-oncological disease (e.g. active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial.
Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days.
Second malignancy currently requiring another anti-cancer therapy.
Absolute neutrophil count less than 1500/mm3.

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
day 1 to day 5low to high dose	Drug	arm B
day 1 to day 14low to high dose	Drug	arm A

Primary outcome

Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study
Time frame: 3 weeks
Occurrence of dose limiting toxicity (DLT) during the first treatment cycle for the treatment Schedules A and B. Some patients excluded from Treated Set (TS) as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.

3 secondary outcomes

Best Overall Response
Time frame: From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013
Objective Response
Time frame: From the start of treatment and the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
Disease Control
Time frame: From the start of treatment to the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.

Results and safety

Results posted to the registry on 21 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Schedule A BI 847325 6 mg (A1)	3	0
Schedule A BI 847325 9 mg (A2)	3	0
Schedule A BI 847325 13 mg (A3)	3	0
Schedule A BI 847325 19 mg (A4)	3	0
Schedule A BI 847325 26 mg (A5)	7	0
Schedule A BI 847325 33 mg (A6)	7	0
Schedule A BI 847325 46 mg (A7)	3	0
Schedule A BI 847325 63 mg (A8)	3	0
Schedule A BI 847325 86 mg (A9)	5	0
Schedule A BI 847325 120 mg (A10)	6	0
Schedule A BI 847325 160 mg (A11)	4	0
Schedule B BI 847325 6 mg (B1)	1	0
Schedule B BI 847325 12 mg (B2)	1	0
Schedule B BI 847325 23 mg (B3)	1	0
Schedule B BI 847325 46 mg (B4)	1	0
Schedule B BI 847325 90 mg (B5)	3	0
Schedule B BI 847325 180 mg (B6)	3	0
Schedule B BI 847325 130 mg (B7)	6	0
Schedule B BI 847325 150 mg (B8)	6	0

Primary outcome: Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study

Time frame: 3 weeks. Number. Unit: Percentage of participants

Measure	Schedule A BI 847325 6 mg (A1) n = 3	Schedule A BI 847325 9 mg (A2) n = 3	Schedule A BI 847325 13 mg (A3) n = 3	Schedule A BI 847325 19 mg (A4) n = 3	Schedule A BI 847325 26 mg (A5) n = 6	Schedule A BI 847325 33 mg (A6) n = 6	Schedule A BI 847325 46 mg (A7) n = 3	Schedule A BI 847325 63 mg (A8) n = 3	Schedule A BI 847325 86 mg (A9) n = 3	Schedule A BI 847325 120 mg (A10) n = 6	Schedule A BI 847325 160 mg (A11) n = 3	Schedule B BI 847325 6 mg (B1) n = 1	Schedule B BI 847325 12 mg (B2) n = 1	Schedule B BI 847325 23 mg (B3) n = 1	Schedule B BI 847325 46 mg (B4) n = 1	Schedule B BI 847325 90 mg (B5) n = 3	Schedule B BI 847325 180 mg (B6) n = 3	Schedule B BI 847325 130 mg (B7) n = 6	Schedule B BI 847325 150 mg (B8) n = 6	Schedule A Total (Total A) n = 42	Schedule B Total (Total B) n = 22	Total Patients n = 64
Value	0	0	0	0	16.7	16.7	0	0	0	16.7	66.7	0	0	0	0	0	66.7	16.7	16.7	11.9	18.2	14.1

Population analysed: Treated Set (TS)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the start date of trial medication up to 21 days after the last administration of BI 847325, up to 266 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Schedule A BI 847325 6 mg (A1)	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Schedule A BI 847325 9 mg (A2)	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Schedule A BI 847325 13 mg (A3)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Schedule A BI 847325 19 mg (A4)	1 of 3 (33.3%)	2 of 3 (66.7%)	Not reported
Schedule A BI 847325 26 mg (A5)	5 of 7 (71.4%)	7 of 7 (100%)	Not reported
Schedule A BI 847325 33 mg (A6)	3 of 7 (42.9%)	7 of 7 (100%)	Not reported
Schedule A BI 847325 46 mg (A7)	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Schedule A BI 847325 63 mg (A8)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Schedule A BI 847325 86 mg (A9)	4 of 5 (80%)	5 of 5 (100%)	Not reported
Schedule A BI 847325 120 mg (A10)	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
Schedule A BI 847325 160 mg (A11)	4 of 4 (100%)	4 of 4 (100%)	Not reported
Schedule A Total (Total A)	22 of 47 (46.8%)	46 of 47 (97.9%)	Not reported
Schedule B BI 847325 6 mg (B1)	1 of 1 (100%)	1 of 1 (100%)	Not reported
Schedule B BI 847325 12 mg (B2)	0 of 1 (0%)	1 of 1 (100%)	Not reported
Schedule B BI 847325 23 mg (B3)	0 of 1 (0%)	1 of 1 (100%)	Not reported
Schedule B BI 847325 46 mg (B4)	0 of 1 (0%)	1 of 1 (100%)	Not reported
Schedule B BI 847325 90 mg (B5)	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Schedule B BI 847325 180 mg (B6)

Limitations and caveats (from the sponsor): As the trial was terminated without commencing Phase Ib, the endpoints of progression-free survival, time to objective response, duration of objective response and duration of disease control were specified as further endpoints for Phase Ia.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 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 day 1 to day 5 and day 1 to day 14 in people with Neoplasms, run by Boehringer Ingelheim at 2 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 13 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 21 Dec 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 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 21 Dec 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?

Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study (time frame: 3 weeks). 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 NCT01324830.

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 21 Dec 2018.