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.

• ClinicalTrials.gov Identifier: NCT01346540
• Recruitment Status: Completed
• First Posted: May 3, 2011
• Results First Posted: September 10, 2018
• Last Update Posted: September 10, 2018
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief 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

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: BIBF 1120; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 14, 2011
• Actual Primary Completion Date: April 25, 2013
• Actual Study Completion Date: January 17, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: BIBF 1120; VEGF inhibitor	Drug: BIBF 1120; VEGF inhibitor
Placebo Comparator: Placebo; BIBF 1120 placebo	Drug: Placebo; BIBF 1120 placebo

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle for the Determination of the Maximum Tolerated Dose (MTD) [ Time Frame: Up to 21 days from first drug administration ]
   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.
2. Maximum Tolerated Dose (MTD) of Nintedanib Added to Cisplatin/Gemcitabine Based on the Occurrence of DLTs During Treatment Cycle 1. [ Time Frame: Up to 21 days from first drug administration ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Italy

1199.82.39004 Boehringer Ingelheim Investigational Site

Milano, Italy

Netherlands

1199.82.3102 Boehringer Ingelheim Investigational Site

Maastricht, Netherlands

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, Spain

United Kingdom

1199.82.4401 Boehringer Ingelheim Investigational Site

London, United Kingdom

1199.82.4402 Boehringer Ingelheim Investigational Site

Manchester, United Kingdom

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01346540
• Other Study ID Numbers: 1199.82; 2010-019707-32 ( EudraCT Number: EudraCT )
• First Posted: May 3, 2011
• Results First Posted: September 10, 2018
• Last Update Posted: September 10, 2018
• Last Verified: August 2018

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Carcinoma, Bronchogenic; Respiratory Tract Diseases; Nintedanib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action