Phase 1
Completed N=70
Phase I Dose Escalation Study of Concomitant BIBF 1120 and BIBW 2992 in Patients With Advanced Solid Tumours.
Neoplasms
Source: ClinicalTrials.gov NCT00998296 ↗
Enrolled (actual)
70
Serious AEs
47.1%
Results posted
Feb 2015
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities — 0.0; 0.0; 0.0; 0.0 percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities |
0.0; 0.0; 0.0; 0.0; 12.5; 33.3 | — |
| SECONDARY Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1 |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0 |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Changes in Safety Laboratory Parameters |
1; 1; 1; 1; 3; 3 | — |
| SECONDARY Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State) |
0.122; 0.0731; 0.0948; 0.0755; 0.112; 0.0762 | — |
| SECONDARY Trough Plasma Concentration of Afatinib at Steady State |
15.5; NA; 19.0; NA; 19.1; NA | — |
| SECONDARY Objective Response (OR) During the Expansion Phase |
22.2; 0.0; 72.2; 85.7; 5.6; 14.3 | — |
| SECONDARY Disease Control (DC) During the Expansion Phase |
83.3; 28.6; 11.1; 57.1; 5.6; 14.3 | — |
| SECONDARY Stable Disease for at Least 12 Weeks During the Expansion Phase |
44.4; 0.0; 50.0; 85.7; 5.6; 14.3 | — |
| SECONDARY Percentage Change in the Tumour Size From Baseline During the Expansion Phase |
1; 3; 4; 3; 6; 0 | — |
Eligibility Criteria
Inclusion criteria
- 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.
- Age 18 years or older.
- Life expectancy of at least three months.
- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
- Patients previously treated and with asymptomatic brain metastases are eligible
- Patients must have recovered from recent surgery.
Exclusion criteria
- Active infectious disease
- Recent surgery within the last 4 weeks prior visit 1.
- Chronic diarrhoea or gastrointestinal tract disease resulting in an inability to take oral medication
- History of haemorrhagic or thrombotic events
- Significant cardiovascular diseases within
- Current peripheral neuropathy > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 except due to trauma
- Untreated or symptomatic brain metastases or leptomeningeal disease.
- Treatment with an Epidermal growth Factor-receptor (EGFR)- or Heregulin Receptor 2 (HER2) inhibiting drug or antiangiogenic drug.
- Therapeutic anticoagulation.
- Female patients of childbearing potential.
- Known pre-existing interstitial lung disease
Data sourced from ClinicalTrials.gov (NCT00998296). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.