Monotherapy Dose Finding With BI 847325 in Solid Tumours

NCT01324830 | Completed Phase 1 Results

• 2 other identifiers: 1287.12010-023832-18
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• 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.

  3 weeks

Secondary Outcomes (3)

• Best Overall Response

  From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013

• Objective Response

  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

  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.

Study Arms (2)

arm A

EXPERIMENTAL

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

arm B

EXPERIMENTAL

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

Drug: day 1 to day 5

Interventions

day 1 to day 5 DRUG

low to high dose

arm B

day 1 to day 14 DRUG

low to high dose

arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• \. 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (2)

1287.1.3201 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1287.1.3202 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

MeSH Terms

Conditions

Neoplasms

Limitations and Caveats

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.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2011
• First Posted: March 29, 2011
• Study Start: April 15, 2011
• Primary Completion: June 6, 2013
• Study Completion: October 10, 2013
• Last Updated: December 21, 2018
• Results First Posted: December 21, 2018

Record last verified: 2018-06

Locations

BE (2)