Monotherapy Dose Finding With BI 847325 in Solid Tumours

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01324830
Recruitment Status : Completed
First Posted : March 29, 2011
Last Update Posted : December 11, 2013
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
The aim of the Phase Ia (dose escalation) part of this trial is to assess the 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 and to assess target modulation and the potential antitumour efficacy in patients with selected tumour types.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: day 1 to day 5 Drug: day 1 to day 14 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : April 2011
Primary Completion Date : October 2013
Study Completion Date : October 2013

Arm Intervention/treatment
Experimental: arm A
14 days once a day oral intake of BI 847325 followed by 7 days break in 3-week cycles
Drug: day 1 to day 14
low to high dose
Experimental: arm B
5 days once daily oral intake of BI 847325 followed by 2 days break, repeated every week
Drug: day 1 to day 5
low to high dose

Primary Outcome Measures :
  1. maximum tolerated dose (MTD) in each of the treatment arms [ Time Frame: average of 18 months ]
  2. number and intensity of adverse events in order to confirm dose level and schedule in 4 pre-specified cancer types [ Time Frame: average of 12 months ]

Secondary Outcome Measures :
  1. Efficacy endpoint in phase Ia part: disease control rate [ Time Frame: every 6 weeks ]
  2. Efficacy endpoint in phase Ia part: objective response [ Time Frame: every 6 weeks ]
  3. Pharmacokinetic parameters of BI 847325 will be determined from plasma and urine analyses after a single oral dose and after repeated dosing, at steady state: Cmax, Tmax, apparent terminal rate constant, t1/2, area under the curve [ Time Frame: average of every 3 months ]
  4. Efficacy endpoint in phase Ib part: Progression Free Survival rate after 6 cycles [ Time Frame: average of 5 months ]
  5. Efficacy endpoint in phase Ib part: Objective Response [ Time Frame: every 6 weeks ]
  6. Efficacy endpoint in phase Ib part: Disease Control Rate [ Time Frame: every 6 weeks ]
  7. Efficacy endpoint in phase Ib part: Best Overall Response [ Time Frame: average of 4 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. 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.
  2. Age 18 years and older
  3. Written informed consent consistent with ICH-GCP and local legislation
  4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  5. 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).
  6. Written informed consent to the use of archival tumour sample for determination of the BRAF/RAS mutational status.
  7. Life expectancy of at least 12 weeks.
  8. In escalation phase, when PK close to predicted Cmax or when signs of 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:

  9. 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.
  10. have a measurable disease.
  11. 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.

Exclusion criteria:

  1. Inability to swallow tablets.
  2. 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.
  3. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days.
  4. Second malignancy currently requiring another anti-cancer therapy.
  5. Absolute neutrophil count less than 1500/mm3.
  6. Platelet count less than 100 000/mm3.
  7. Bilirubin greater than 1.5 mg/dL (>26 µmol/L, SI unit equivalent) (except known Gilbert's syndrome).
  8. 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).
  9. Serum creatinine greater than 1.5 mg/dL (>132 µmol/L, SI unit equivalent).
  10. Previous episode of QT prolongation due to a medication which, as a result of it, had to be discontinued; or long QT syndrome; or QTc with Fridericia's correction >480 msec on screening ECG.
  11. Pregnancy or breastfeeding.
  12. Women or men who are sexually active and unwilling to use a medically acceptable method of contraception.
  13. 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.
  14. 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 LHRH agonists, steroids and bisphosphonates.
  15. Patients unable to comply with the protocol.
  16. Active alcohol or drug abuse.
  17. history or presence of cardiovascular abnormalities deemed clinically relevant by the investigator. Myocardial infarction within 6 months prior to study.
  18. Cardiac left ventricular ejection fraction <50% or less than institutional lower limit of normal by MUGA or echocardiography

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01324830

1287.1.3201 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1287.1.3202 Boehringer Ingelheim Investigational Site
Leuven, Belgium
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Responsible Party: Boehringer Ingelheim Identifier: NCT01324830     History of Changes
Other Study ID Numbers: 1287.1
2010-023832-18 ( EudraCT Number: EudraCT )
First Posted: March 29, 2011    Key Record Dates
Last Update Posted: December 11, 2013
Last Verified: December 2013