Nintedanib and Weekly Docetaxel in Lung Adenocarcinoma

Study Overview
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Brief Summary
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Phase I study. To determine the MTD (Maximum Tolerated Dose) of nintedanib + weekly Docetaxel in patients with locally advanced or metastatic lung adenocarcinoma after failure of platinum-based first line chemotherapy.

Official Title
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An Open Label Phase I of Oral Nintedanib Plus Weekly Docetaxel Therapy in Patients With Locally Advanced or Metastatic Lung Adenocarcinoma After Failure of Platinum -Based First Line Chemotherapy

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Nintedanib
* Drug: Nintedanib
* Drug: Nintedanib
* Drug: Nintedanib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: -Patients with histologically/ cytologically confirmed locally advanced (Stage IIIB) or metastatic (Stage IV) lung adeno carcinoma after failure of first line platinum - based chemotherapy (patients with non-target lesion only are eligible). First line chemotherapy may include continuation or switch maintenance therapy. One prior adjuvant and/or neoadjuvant chemotherapy line is accepted. Prior immunotherapy is allowed. ECOG inferior or equal to 1 at screening. Further inclusion criteria apply Exclusion criteria: Patients who have received more than one prior line of chemotherapy (i.e. second or third line chemotherapy) for advanced or metastatic NSCLC. Patients known to be positive for activating Epidermal Growth Factor Receptor (EGFR) mutation or patients known to be positive for ALK translocation Further exclusion criteria apply.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Level 0<br>Nintedanib low dose with docetaxel | Drug: Docetaxel<br> <br> Drug: Nintedanib<br>* Low Dose<br>|
| Other: Level 1<br>Nintedanib medium dose with docetaxel | Drug: Docetaxel<br> <br> Drug: Nintedanib<br>* Medium dose<br>|
| Other: Level 2<br>Nintedanib high dose with docetaxel | Drug: Docetaxel<br> <br> Drug: Nintedanib<br>* High dose<br>|
| Other: Level 3<br>Nintedanib continuous high dose with docetaxel | Drug: Docetaxel<br> <br> Drug: Nintedanib<br>* Continuous high dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Nintedanib Administered in Combination With Docetaxel | Maximum tolerated dose (MTD) of nintedanib administered in combination with docetaxel. The MTD was defined as the highest dose combination studied for which the incidence of DLTs was no more than 1 out of 6 subjects experiencing a DLT during the first treatment cycle i.e. the incidence of DLTs was no more than 17%. In case dose escalation reached dose level 3 (200 mg bid nintedanib administered without interruption on days of docetaxel infusion) and no more than 1 out of 6 subjects experienced a DLT during the first 28-day cycle at this dose level, dose level 3 was considered the MTD. | First treatment cycle, the first 28 days following the start of trial medication. | 
| Number of Participants With Dose-limiting Toxicity (DLT) During the First Treatment Cycle | Number of participants with DLT occurring during the first treatment cycle. DLT was defined as any of the following adverse events related to nintedanib: Non-haematological drug-related Common Terminology Criteria for AEs (CTCAE) grade 3 or greater diarrhoea CTCAE grade 2 for >7 days despite supportive care nausea CTCAE grade 3 or greater despite supportive care vomiting CTCAE grade 2 or greater despite supportive care increase in Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) to CTCAE grade 3 or greater A increase in ALT and/or AST to CTCAE grade 2 or greater in conjunction with total bilirubin increase of CTCAE grade 1 or greater Platelets <50 000/mm3 with bleeding (CTCAE ≥3) neutropenia of any grade or duration accompanied by fever >38.5°C neutropenia grade 4 without fever of >7 days duration Inability to resume nintedanib dosing within 21 days after stopping due to toxicity. | First treatment cycle, the first 28 days following the start of trial medication. |