Clinical trial NCT00998296: Phase I Dose Escalation Study of Concomitant BIBF 1120 and BIBW 2992 in Patients With Advanced Solid Tumours.
Official title: Phase I Dose Escalation Study of Concomitant BIBF 1120 and BIBW 2992 in Patients With Advanced Solid Tumours.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-10-20
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to determine the Maximum Tolerated Dose (MTD) of the combination of BIBW 2992/BIBF 1120 therapy administered concomitantly. The MTD will provide dosing recommendation for subsequent phase II trials in patients with metastatic cancer.


Eligibility criteria: Inclusion criteria:

1. Patients with confirmed histological or cytological diagnosis of advanced solid tumours and for whom no proven therapy exists or who are not amenable to established treatments.
2. Age 18 years or older.
3. Life expectancy of at least three months.
4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
5. Patients previously treated and with asymptomatic brain metastases are eligible
6. Patients must have recovered from recent surgery.

Exclusion criteria:

1. Active infectious disease
2. Recent surgery within the last 4 weeks prior visit 1.
3. Chronic diarrhoea or gastrointestinal tract disease resulting in an inability to take oral medication
4. History of haemorrhagic or thrombotic events
5. Significant cardiovascular diseases within
6. Current peripheral neuropathy \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1 except due to trauma
7. Untreated or symptomatic brain metastases or leptomeningeal disease.
8. Treatment with an Epidermal growth Factor-receptor (EGFR)- or Heregulin Receptor 2 (HER2) inhibiting drug or antiangiogenic drug.
9. Therapeutic anticoagulation.
10. Female patients of childbearing potential.
11. Known pre-existing interstitial lung disease

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities
timeFrame: first treatment cycle, up to 28 days
Secondary outcomes:
measure: Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
timeFrame: 6 weeks
measure: Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0
timeFrame: First treatment administration until cut-off date of 02Oct2014; up to 336 days
measure: Changes in Safety Laboratory Parameters
timeFrame: First treatment administration until cut-off date of 02 October 2014, up to 336 days
measure: Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State)
timeFrame: Day 8, Day 15, Day 22 and Day 28
measure: Trough Plasma Concentration of Afatinib at Steady State
timeFrame: Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28
measure: Objective Response (OR) During the Expansion Phase
timeFrame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
measure: Disease Control (DC) During the Expansion Phase
timeFrame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
measure: Stable Disease for at Least 12 Weeks During the Expansion Phase
timeFrame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
measure: Percentage Change in the Tumour Size From Baseline During the Expansion Phase
timeFrame: Tumour assessment was to be performed at Screening, every 6 weeks after starting study treatment until disease progression, and at the end-of-treatment (EOT) visit (up to 1117 days)
Other outcomes:
Locations:
city: Villejuif Cedex
country: France
facility: 1239.14.3301A Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Bahleda R, Hollebecque A, Varga A, Gazzah A, Massard C, Deutsch E, Amellal N, Farace F, Ould-Kaci M, Roux F, Marzin K, Soria JC. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours. Br J Cancer. 2015 Nov 17;113(10):1413-20. doi: 10.1038/bjc.2015.374. Epub 2015 Oct 29.