Monotherapy Dose Finding With BI 847325 in Solid Tumours

NCT ID: NCT01324830

Last Updated: 2018-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-15
• Study Completion Date: 2013-10-10

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.

Conditions

Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

arm A

14 days once a day oral intake of BI 847325 followed by 7 days break in 3-week cycles

Group Type: EXPERIMENTAL

day 1 to day 14

Intervention Type: DRUG

low to high dose

arm B

5 days once daily oral intake of BI 847325 followed by 2 days break, repeated every week

Group Type: EXPERIMENTAL

day 1 to day 5

Intervention Type: DRUG

low to high dose

Interventions

day 1 to day 5

low to high dose

Intervention Type: DRUG

day 1 to day 14

low to high dose

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1287.1.3201 Boehringer Ingelheim Investigational Site

Brussels, , Belgium

1287.1.3202 Boehringer Ingelheim Investigational Site

Leuven, , Belgium

Countries

Belgium

Other Identifiers

2010-023832-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1287.1

Identifier Type: -

Identifier Source: org_study_id