Relpased advanced or metastatic non-small cell lung cancer of adenocarcinoma histology MedDRA version: 19.1 Level: PT Classification code 10025033 Term: Lung adenocarcinoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.1 Level: PT Classification code 10064049 Term: Lung adenocarcinoma metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.
Conditions
Interventions
Trade Name: VARGATEF
Product Name: VARGATEF
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib esylate
CAS Number: 656247-18-6
Current Sponsor code: BIBF 1120
Concentration unit: mg mi
Sponsors
Royal Marsden NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be enrolled in the study: 1. Male or female patients aged 18 or over. 2. Patients with a pathologically confirmed diagnosis of stage III or stage IV adenocarcinoma of the lung; patients with locally recurrent disease (stage IIIa) and no radical treatment options are also eligible. 3. Patients who have previously received no more than 2 lines of systemic therapy for NSCLC with palliative intent: i. Chemotherapy as first-line or more with palliative intent ii. Relapsing within 6 months of adjuvant chemotherapy after surgery or as part of radical chemo-radiotherapy, which count as one line of therapy. iii. Licenced or experimental maintenance therapy is allowed (eg.pemetrexed) iv. Immunotherapy at prior line of treatment (first or second line) is allowed. 4. Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 5. Patients with estimated life expectancy of = 12 weeks. 6. Patients with at least one radiologically measurable tumour lesion as defined by RECIST 1.1 criteria. 7. Patients with adequate haematopoietic, hepatic and renal function. 8. Signed informed consent in accordance with ICH-GCP guidelines and local legislation. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 68 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 126
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a patient from enrolment: 1. Patients with a known EGFR kinase sensitising mutation or ALK gene fusion prior to enrolment who have not received prior TKI (patients enrolled and subsequently found to be positive will remain on protocol). Patients with a known EGFR activating mutation or ALK fusion who have received appropriate TKI therapy will be allowed. 2. Any concurrent anticancer systemic therapy. 3. Prior treatment with nintedanib or any other VEGFR inhibitor; prior treatment with bevacizumab is allowed. 4. Patients refractory to prior Taxane therapy for advanced disease. Prior taxane used in the adjuvant setting does not exclude eligibility provided there is no disease recurrence within 12 months upon completion of chemotherapy in that setting. 5. Adequate laboratory parameters defined by: i. Absolute neutrophil count (ANC) 1.5 x ULN in patients without liver metastasis. vii. ALT and/or AST > 2.5 x ULN in patients with liver metastasis. viii. International normalised ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN. 6. Proteinuria CTCAE grade 2 or greater. 7. Pre-existing peripheral sensory neuropathy CTCAE grade 2 or greater. 8. Use of any investigational drug within 4 weeks of randomisation. 9. Radiotherapy within 4 weeks prior to randomisation. 10. Major surgery (other than biopsy) within 4 weeks prior to randomisation. 11. Active brain metastases or leptomeningeal disease (defined as stable for NYHA II, serious cardiac arrhythmia, pericardial effusion). d. Gastro-intestinal abnormalities, including inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption, any medical co-morbidity affecting gastrointestinal absorption. e. History of clinically significant haemorrhagic or thromboembolic event in the past 6 months. f. Known inherited predisposition to bleeding or thrombosis. g. Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period. h. Drug or alcohol abuse. 14. Therapeutic anticoagulation (except
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study is divided into 2 parts: Part 1 is the Phase Ib portion of the trial and Part 2 is the Phase II portion of the trial. Once the Trial Steering Committee has completed the dose limiting toxicity (DLT) assessment for Part 1 and confirmed RP2D for Part 2, Part 2 enrolment will proceed. The objective(s) for each part are as follows: Part 1: The objective of Part 1 is to evaluate the safety and tolerability of combination nab-paclitaxel and nintedanib in patients with stage IIIb and IV adenocarcinoma of the lung in second and third treatment line setting and to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of nintedanib when given with nab-paclitaxel at 100mg/m2 d1, d8 q21. Part 2: The primary objective of Part 2 is to explore the efficacy of combination nab-paclitaxel and nintedanib versus nab-paclitaxel and placebo in the same patient population, with nintedanib/placebo given at the recommended phase 2 dose (RP2D) as defined during part 1 of the stu;Secondary Objective: Secondary objectives for Part 1: • To examine the frequency of all adverse events graded by NCI-CTCAE version 4.0. • To examine the objective tumour response according to RECIST 1.1 criteria (investigator reported), and the overall response rate •To explore the number of cycles of nab-paclitaxel with nintedanib given Secondary objectives for Part 2: • To examine the frequency of all adverse events graded by NCI-CTCAE version 4.0. • To examine the objective tumour response according to RECIST 1.1 criteria (investigator reported), and the overall response rate. • To examine overall survival in the intention to treat population and in two predefined subgroups: according to progressive disease before or after 9 months from start of first line systemic therapy; and according to prior or no prior immunotherapy. ;Primary end point(s): The study is divided into 2 parts. Part 1 is the Phase Ib portion of the trial and Part 2 is the Phase II portion of the | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate the frequency of all adverse events graded by NCI-CTCAE version 4.0 - To define number of cycles of nintedanib and nab-paclitaxel given - To evaluate the objective tumour response and overall response rates by RECIST version 1.1 - To explore the overall survival rates by treatment arm in ITT and predefined subgroups by time to progression after start of 1st line treatment and by previous immunotherapy ;Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
United Kingdom
Contacts
Public ContactSally Ellis
Royal Marsden NHS Foundation Trust
Outcome results
None listed