Trial Outcomes & Findings for 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. (NCT NCT01346540)

Last Updated: 2025-02-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Up to 21 days from first drug administration

Results posted on

2025-02-12

Participant Flow

Phase I was open-label, 3+3 dose-confirmation part of the trial aimed to confirm safety of nintedanib to a maximum dose of 200 milligram twice daily given in combination with the standard regimen of gemcitabine and cisplatin. Phase II was to be double-blind, randomised, placebo-controlled part, but this part of the trial was not conducted.

Participant milestones

Participant milestones
Measure	Nintedanib 150 Milligram Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.
Overall Study STARTED	4	12
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	3	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Nintedanib 150 Milligram Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.
Overall Study Progressive disease-RECIST 1.1 criteria	3	8
Overall Study Adverse Event	0	4

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nintedanib 150 Milligram n=4 Participants Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram n=12 Participants Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Total n=16 Participants Total of all reporting groups
Age, Continuous	64.5 Years STANDARD_DEVIATION 10.9 • n=99 Participants	65.7 Years STANDARD_DEVIATION 5.0 • n=107 Participants	65.4 Years STANDARD_DEVIATION 6.5 • n=206 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Sex: Female, Male Male	4 Participants n=99 Participants	11 Participants n=107 Participants	15 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to 21 days from first drug administration

Population: All patients who received at least one dose of nintedanib were included in the Safety Set.

Outcome measures

Outcome measures
Measure	Nintedanib 150 Milligram n=4 Participants Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram n=12 Participants Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.
Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle for the Determination of the Maximum Tolerated Dose (MTD)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 21 days from first drug administration

Population: All patients who received at least one dose of nintedanib were included in the Safety Set.

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.

Outcome measures

Outcome measures
Measure	Nintedanib 150 Milligram n=16 Participants Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.
Maximum Tolerated Dose (MTD) of Nintedanib Added to Cisplatin/Gemcitabine Based on the Occurrence of DLTs During Treatment Cycle 1.	200 Milligram	—

SECONDARY outcome

Timeframe: From the first drug administration until 28 days after last study drug administration, up to 804 days

Population: Treated Set

Incidence of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 with grade 1-5.

Outcome measures

Outcome measures
Measure	Nintedanib 150 Milligram n=4 Participants Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram n=12 Participants Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.
Incidence of Adverse Events (AEs) According to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 Grade 3	1 Participants	8 Participants
Incidence of Adverse Events (AEs) According to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 Grade 1	0 Participants	0 Participants
Incidence of Adverse Events (AEs) According to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 Grade 2	0 Participants	0 Participants
Incidence of Adverse Events (AEs) According to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 Grade 4	3 Participants	2 Participants
Incidence of Adverse Events (AEs) According to the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.00 Grade 5	0 Participants	2 Participants

Adverse Events

Nintedanib 150 Milligram

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Nintedanib 200 Milligram

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Nintedanib 150 Milligram n=4 participants at risk Patient received 150 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.	Nintedanib 200 Milligram n=12 participants at risk Patient received 200 milligram (mg) Nintedanib (BIBF 1120) soft gelatin capsules, administered orally twice daily until withdrawal criteria were fulfilled along with standard therapy of Gemcitabine and Cisplatin. Gemcitabine was administered as an intravenous infused dose of 1250 milligram per meter squared (mg/m2) on days 1 and 8 of each 21-day treatment cycle. Cisplatin was administered as an intravenous infused dose of 75 mg/m2 given on day 1 of each 21-day treatment cycle.
Blood and lymphatic system disorders Thrombocytopenia	25.0% 1/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	0.00% 0/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	0.00% 0/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Gastrointestinal disorders Dysphagia	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Gastrointestinal disorders Vomiting	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
General disorders Fatigue	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
General disorders Sudden death	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Infections and infestations Lower respiratory tract infection	25.0% 1/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	0.00% 0/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Infections and infestations Pneumonia	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	16.7% 2/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Infections and infestations Respiratory tract infection	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis carcinomatosa	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Renal and urinary disorders Renal failure	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	16.7% 2/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.
Vascular disorders Deep vein thrombosis	0.00% 0/4 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.	8.3% 1/12 • From the first drug administration until 28 days after last study drug administration, up to 804 days Adverse events ongoing from the end of the treatment visit were also captured.