Clinical Trials Register

Summary
EudraCT Number:	2017-000659-23
Sponsor's Protocol Code Number:	220365-2017
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-30
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2017-000659-23

A.3

Full title of the trial

A Safety and feasibility study of standard dosing day 1 carboplatin AUC 5 every 3rd weeks with daily Navelbine® 20/30mg (oral) during 4 cycles (12 weeks) for the treatment of advanced NSCLC; A feasibility study

Sikkerheds- og effektstudie af standard (st.) dosering af carboplatin dag 1 hver 3. uge plus daglig Navelbine® 20/30 mg (oral) i løbet af 4 cykler (12 uger) til behandling af fremskreden ikke små-cellet lungekræft; Et pilot studie

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

NavMetro protocol

A.4.1

Sponsor's protocol code number

220365-2017

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Aarhus University Hospital
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Aarhus University Hospital (AUH) Oncology dep
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Aarhus University Hospital (AUH)
B.5.2	Functional name of contact point	Clinical Research Unit (KFE)
B.5.3	Address:
B.5.3.1	Street Address	Department of Oncology, Aarhus University Hospital, Noerrebrogade 44 byg. 19 Z
B.5.3.2	Town/ city	Aarhus C
B.5.3.3	Post code	8000
B.5.3.4	Country	Denmark
B.5.6	E-mail	marikand@rm.dk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Navelbine
D.2.1.1.2	Name of the Marketing Authorisation holder	Pierre Fabre Pharma Norden AB, Turebergs Torg 1, plan 2 S-191 47 Sollentuna, Sweden
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VINORELBINE TARTRATE
D.3.9.1	CAS number	125317-39-7
D.3.9.2	Current sponsor code	220365-2017
D.3.9.4	EV Substance Code	SUB20777
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	30 to 20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with metastatic or locally advanced Non-small-cell lung cancer (NSCLC)

Ikke-småcellet lungecancer hos voksne patienter

E.1.1.1

Medical condition in easily understood language

Patients with incurable lung cancer.

Uheldbredelig lungecancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10025044
E.1.2	Term	Lung cancer
E.1.2	System Organ Class	100000015855

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10025055
E.1.2	Term	Lung cancer non-small cell stage IV
E.1.2	System Organ Class	100000015841

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objectives:
Evaluating the side effects (toxicity and feasibility, adverse events grade 2-5 (CTC)) during the first 84 days (12 weeks) of treatment.

E.2.2

Secondary objectives of the trial

Secondary Objectives:
Progression-free survival (PFS)
The Disease Control Rate (CR + PR + SD, (SD > 4 months)).
The duration of Disease Control
Time to progression (TTP).
The response rate (RR).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Written (personally dated and signed) informed consent.
2. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and/or the follow-up schedule.
3. ECOG performance status 0-1 (also PS 2 after the first 6 patients if acceptable toxicity according to chapter 8: Toxicity and dose modifications.
4. Life expectancy ≥ 10 weeks
5. Cytological or Histological confirmed squamous and non-squamous NSCLC in 1st or 2nd line where the investigator finds the patient suitable.
6. First line in stage IV NSCLC and in stage IIIB not suitable for curative treatment. Second line after immunotherapy (minimum 3 weeks after the last immunotherapy).
7. Presence of ≥ 1 measurable lesion as per RECIST 1.1 which has not been previously irradiated.
8. Adequate bone marrow, hepatic and renal function as defined by the following laboratory values:
•Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
•Platelet count ≥ 100 x 109/L.
•Haemoglobin ≥ 10 g/dL or ≥ 6.2 mmol/L.
•Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN in case of liver metastases).
•Liver transaminases ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases).
•Alkaline phosphatase ≤ 5 x ULN.
•Adequate renal function
9. Palliative radiotherapy can be allowed but not to the sites used for evaluation of response. (See section 4.4).
10. Fertile men should use effective contraceptive prevention. Fertile women must be using a medically accepted method of contraception to avoid pregnancy during 2 months preceding registration, throughout the study period and up to 3 months after last dose of study treatment in such a manner that the risk of pregnancy is minimized. Women who may be pregnant should have a pregnancy test.

E.4

Principal exclusion criteria

1. Patients with NSCLC disease suitable for curable treatment.
2. No recovery to ≥ G1 side effects (exception: alopecia) of any prior anti-neoplastic treatment.
3. Current peripheral neuropathy ≥ G2.
4. Dysphagia or inability to swallow oral medication.
5. Malabsorption syndrome or disease significantly affecting GI-function or major resection of the stomach or proximal small bowel that could affect absorption of oral vinorelbine.
6. Other serious illness or medical condition, such as but not limited to:
a. Clinically significant cardiac disease or impaired cardiac function (such as: uncontrolled congestive heart failure requiring treatment; significant cardiac arrhythmia; conduction abnormality such as congenital long QT syndrome or high grade/complete AV-blockage; myocardial infarction within the previous 3 months, unstable angina pectoris, coronary artery bypass graft, coronary angioplasty or stenting, if < 3 months prior to registration; QTcF >480 msec at screening)
7. Unstable diabetes mellitus.
8. Uncontrolled hypercalcemia.
9. Clinically significant active infections (current or within the last 2 weeks prior to registration).
10. Previous organ allograft.
11. Concomitant treatment with strong CYP3A4-inhibitors or strong CYP3A4-inducers (discontinuation before registration is acceptable, if medically feasible and ethically acceptable).
12. Pregnant women.

E.5 End points

E.5.1

Primary end point(s)

Metronomic chemotherapy is not yet well validated in the clinic, and we still need to identify the best medications and optimal dosage and regimens.
By developing an effective oral treatment with frequent, daily doses of Navelbine Oral, we expect to achieve the same therapeutic benefit against the disease, as achieved by higher dose of Navelbine, twice in three weeks, but with less toxicity.

E.5.1.1

Timepoint(s) of evaluation of this end point

The end of this trial will be reached at 4 months after last patient last treatment. There will be included 20 patients in this study.

E.5.2

Secondary end point(s)

Progression-free survival (PFS)
The Disease Control Rate (CR + PR + SD, (SD > 4 months)).
The duration of Disease Control
Time to progression (TTP).
The response rate (RR).

E.5.2.1

Timepoint(s) of evaluation of this end point

The end of this trial will be reached at 4 months after last patient last treatment. There will be included 20 patients in this study.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of this trial will be reached at 4 months after last patient last treatment.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-10-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-10-08

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