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.

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01346540
• Other study ID #: 1199.82
• Secondary ID: 2010-019707-32
• Status: Completed
• Phase: Phase 1
• Start date: April 14, 2011
• Est. completion date: January 17, 2017

Study information

• Verified date: August 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 17, 2017
• Est. primary completion date: April 25, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

Run-in Phase I

1. Histologically or cytologically confirmed diagnosis of stage IIIB/IV or recurrent Non Small Cell Lung Cancer (NSCLC) with squamous cell histology.

2. Measurable disease according to Response Evaluation Criteria in Solid Tumours ( RECIST 1.1).

3. Patient Eastern Cooperative Oncology Group (ECOG) score of 0-1.

4. Male or female patients age = 18 years.

5. Life expectancy of at least three (3) months.

6. Written informed consent in accordance with International Conference on Harmonisation

• Good Clinical Practice (ICH-GCP) guidelines.

Phase II - in addition to the above criteria:

7. Radiologically-confirmed at least stable disease after 2 prior cycles of cisplatin / gemcitabine chemotherapy.

Exclusion criteria:

1. 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

2. Prior treatment with other Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors (other than bevacizumab)

3. Any contraindications for treatment with gemcitabine and/or cisplatin.

4. Use of any investigational drug within 4 weeks of entering the 1199.82 study.

5. History of major thrombotic or clinically relevant bleeding event in the past 6 months.

6. Significant cardiovascular diseases (i.e. hypertension not controlled by medication.

7. Surgery within 4 weeks (except tumour biopsy) prior randomisation and incomplete wound healing.

8. Active brain metastases

9. Radiotherapy (except extremities) within 3 months prior to baseline imaging and radiotherapy for brain metastasis < 4 weeks prior baseline imaging.

10. Any other current malignancy or malignancy diagnosed within the past five (5) years.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• BIBF 1120
VEGF inhibitor
• Placebo
BIBF 1120 placebo

Locations

Country	Name	City	State
Italy	1199.82.39004 Boehringer Ingelheim Investigational Site	Milano
Netherlands	1199.82.3102 Boehringer Ingelheim Investigational Site	Maastricht
Spain	1199.82.3401 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1199.82.3406 Boehringer Ingelheim Investigational Site	Madrid
Spain	1199.82.3410 Boehringer Ingelheim Investigational Site	Málaga
United Kingdom	1199.82.4401 Boehringer Ingelheim Investigational Site	London
United Kingdom	1199.82.4402 Boehringer Ingelheim Investigational Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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

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