Clinical trial NCT01324830: Monotherapy Dose Finding With BI 847325 in Solid Tumours
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-03-29
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 and to assess target modulation and the potential antitumour efficacy in patients with selected tumour types.


Eligibility criteria: 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 International conference on harmonization - Good clinical practice (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/Tat sarcoma viral oncogene homolog (RAS) mutational status.
7. Life expectancy of at least 12 weeks.
8. 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:
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, Système international (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 corrected QT interval (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 Luteinizing hormone-releasing hormone (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 Multiple Gated Acquisition scan (MUGA) or echocardiography

Primary outcomes:
measure: Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study
timeFrame: 3 weeks
Secondary outcomes:
measure: Best Overall Response
timeFrame: From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013
measure: Objective Response
timeFrame: 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.
measure: Disease Control
timeFrame: 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.
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: 1287.1.3201 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1287.1.3202 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: