A Phase I/II Study of Continuous Oral Treatment With BIBF 1120 Added to Standard Gemcitabine/Cisplatin Therapy in First Line NSCLC Patients With Squamous Cell Histology.

Study Overview
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Brief Summary
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The LUME-Lung3 study is in 2 parts: Run-in Phase I - Open label study to identify the Maximum Tolerated Dose of BIBF 1120 that can be added to standard first-line treatment with 3 weekly schedules of gemcitabine and cisplatin. Phase II - Placebo controlled efficacy study of BIBF 1120 added to standard 3 weekly cycles of gemcitabine and cisplatin therapy in patients with at least Stable Disease after 2 previous courses of the chemotherapy

Official Title
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LUME-Lung 3: A Phase I/II Study of Continuous Oral Treatment With BIBF 1120 Added to Standard Gemcitabine/Cisplatin Therapy in First Line NSCLC Patients With Squamous Cell Histology

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: BIBF 1120
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Run-in Phase I Histologically or cytologically confirmed diagnosis of stage IIIB/IV or recurrent Non Small Cell Lung Cancer (NSCLC) with squamous cell histology. Measurable disease according to Response Evaluation Criteria in Solid Tumours ( RECIST 1.1). Patient Eastern Cooperative Oncology Group (ECOG) score of 0-1. Male or female patients age = 18 years. Life expectancy of at least three (3) months. Written informed consent in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines. Phase II - in addition to the above criteria: Radiologically-confirmed at least stable disease after 2 prior cycles of cisplatin / gemcitabine chemotherapy. Exclusion criteria: Prior therapy for advanced or metastatic or recurrent Non Small Cell Lung Cancer (NSCLC). One prior adjuvant, neoadjuvant or adjuvant + neoadjuvant treatment is allowed if at least 12 months have elapsed between the end of the treatment and randomization Prior treatment with other Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors (other than bevacizumab) Any contraindications for treatment with gemcitabine and/or cisplatin. Use of any investigational drug within 4 weeks of entering the 1199.82 study. History of major thrombotic or clinically relevant bleeding event in the past 6 months. Significant cardiovascular diseases (i.e. hypertension not controlled by medication. Surgery within 4 weeks (except tumour biopsy) prior randomisation and incomplete wound healing. Active brain metastases Radiotherapy (except extremities) within 3 months prior to baseline imaging and radiotherapy for brain metastasis < 4 weeks prior baseline imaging. Any other current malignancy or malignancy diagnosed within the past five (5) years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBF 1120<br>VEGF inhibitor | Drug: BIBF 1120<br>* VEGF inhibitor<br>|
| Placebo Comparator: Placebo<br>BIBF 1120 placebo | Drug: Placebo<br>* BIBF 1120 placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle for the Determination of the Maximum Tolerated Dose (MTD) | The following drug-related adverse events (AEs) qualified as a DLT: Non-hematological toxicity - Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 events excluding transient electrolyte abnormality, hyperuricemia and isolated elevation of gamma-glutamyl trans-peptidase. Gastrointestinal AEs (nausea, vomiting, diarrhoea, abdominal pain) or hypertension of CTCAE Grade ≥3 despite optimal supportive care/intervention. Alanine aminotransferase and or Aspartate aminotransferase elevation of CTCAE Grade ≥3. Haematological toxicity - Uncomplicated CTCAE Grade 4 neutropenia (that was not associated with fever of ≥38.5° Celsius) for >7 days (except during Cycle 1). CTCAE Grade 4 febrile neutropenia associated with fever ≥38.5º Celsius. A decrease in platelet levels to CTCAE Grade 4 or CTCAE Grade 3 associated with bleeding or requiring transfusion. The inability to resume nintedanib dosing within 14 days of stopping due to a drug-related AE was also considered a DLT. | Up to 21 days from first drug administration | 
| Maximum Tolerated Dose (MTD) of Nintedanib Added to Cisplatin/Gemcitabine Based on the Occurrence of DLTs During Treatment Cycle 1. | The MTD was defined as the dose of nintedanib administered with gemcitabine/cisplatin at which no more than 1 of 6 patients experienced DLT (or one dose tier below that dose at which 2 or more of 6 patients experienced DLT) during the first 21-day treatment cycle. Any DLTs experienced after the start of the second treatment period were considered separately. | Up to 21 days from first drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) According to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 | Incidence of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 with grade 1-5. | From the first drug administration until 28 days after last study drug administration, up to 804 days |