Clinical Trials Register

Summary
EudraCT Number:	2010-023688-16
Sponsor's Protocol Code Number:	C-III-002
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-01-12
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

Germany - BfArM

A.2

EudraCT number

2010-023688-16

A.3

Full title of the trial

An Open-Label, Randomized, Parallel Group Study of Patients Treated with Paclitaxel with Standard Dosing versus Pharmacokinetic Guided Dose Adjustment in Patients with Advanced NSCLC

A.3.1

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

An Open-Label, Randomized, Parallel Group Study of Patients Treated with Paclitaxel with Standard Dosing versus Pharmacokinetic Guided Dose Adjustment in Patients with Advanced NSCLC

A.3.2

Name or abbreviated title of the trial where available

CEPAC-TDM

A.4.1

Sponsor's protocol code number

C-III-002

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	CESAR Central European Society for Anticancer Drug Research-EWIV
B.1.3.4	Country	Austria
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	SALADAX Biomedical
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CESAR
B.5.2	Functional name of contact point	Clinical trials information
B.5.3	Address:
B.5.3.1	Street Address	Hanglüssgasse 3
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1150
B.5.3.4	Country	Austria
B.5.4	Telephone number	00431522309312

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	Various marketing authorization holder. Cesar has no influence which Paclitaxel is used in course of this trial
D.2.1.1.2	Name of the Marketing Authorisation holder	see D2.1.1.1
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.1	Product name	Paclitaxel
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	various ptx used in study
D.3.9.1	CAS number	33069--62-4
D.3.9.3	Other descriptive name	paclitaxel
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
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

Stage III-IV Non Small Cell Lung Cancer (NSCLC)

E.1.1.1

Medical condition in easily understood language

Advanced lung cancer

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10025054
E.1.2	Term	Lung cancer non-small cell stage IIIB
E.1.2	System Organ Class	100000004864

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the CEPAC-TDM study is to apply individualized paclitaxel dosing in patients with advanced NSCLC, as defined in Section 1.4. By applying the prespecified dosing algorithm, grade 4 neutropenia is predicted to be reduced from 15% with conventional dosing (i.e. paclitaxel 200 mg/m2 in combination with carboplatin or cisplatin at the predefined dose, given every three weeks) (Arm A) to 4% with individualized paclitaxel dosing (in combination with carboplatin or cisplatin at the predefined dose, given every three weeks) (Arm B) during the second treatment cycle. At the same time, progression-free survival (PFS) and overall survival (OS) must not be affected by individualized paclitaxel dosing.

E.2.2

Secondary objectives of the trial

• Objective tumor response according to RECIST version 1.1
• Progression free survival (PFS)
• Overall survival (OS)
• Overall neutropenia ( i.e. during total chemotherapy duration) assessed from clinical hematology data and by model-based estimations of individual neutrophil curves
• Hematological (leucocytopenia, anemia, thrombocytopenia) and non-hematological toxicites (e.g. neurological, musculosceletal and gastrointestinal adverse events)
• Cumulative dose and dose intensity of paclitaxel and platinum drug
• Incidence of changes from cisplatin to carboplatin and reasons thereof
• Overall rate of febrile neutropenia and hospitalization due to chemotherapy-associated adverse events
• Health economic analysis

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

The genetic Substudy is incorporated in the main study protocol and therefore does not have its own title.
•Which genes differentiate patients experiencing severe neutropenia from those experiencing mild neutropenia
•Which genes differentiate chemotherapy responders from non-responders
•What are the within-patient gene variations before treatment and at the end of treatment
•Which genes differentiate patients with a short disease-free survival from those with a long disease-free survival
•Which genes differentiate patients with severe treatment-associated toxicity from those with no or mild treatment-associated toxicity
•Which genes differentiate patients with a short overall survival from those with a long overall survival

E.3

Principal inclusion criteria

(1)Capable of understanding the protocol requirements and risks, and providing written informed consent.
(2)Patients with histologically confirmed NSCLC (stage IIIB-IV).
(3)Patients considered for first-line palliative chemotherapy with paclitaxel in combination with either cisplatin or carboplatin. Patients having received prior adjuvant non taxane-containing adjuvant chemotherapy are eligible.
(4)At least one bidimensionally measurable lesion according to RECIST 1.1.
(5)ECOG Performance Status (ECOG-PS) status ≤ 2.
(6)Female or male patients of 18 to 75 years of age at randomization
(7)Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods (condom).
(8)An absolute neutrophil count >1,500 cells/ mm3 (= 1.5 G/l).
(9)Platelet count > 100,000/mm3.
(10)Total bilirubin ≤ 2 x upper limit of normal.
(11)AST and ALT ≤ 2.5 x upper limit of normal, or ≤ 5 x upper limit of normal in case of liver metastases.
(12)Creatinine clearance (according to the Cockroft-Gault formula) ≥30ml/min. For patients planned to receive Cisplatin: Creatinine clearance ≥60ml/min.
(13)Patients suffering from asymptomatic brain metastases can be enrolled in case corticosteroid therapy is not indicated. Prior irradiation must be completed at least 4 weeks prior to first cycle of treatment.

E.4

Principal exclusion criteria

(1)Serious concomitant systemic disorders (e.g., active infection, severe heart disease, uncontrolled hypertension or diabetes mellitus) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient’s ability to complete the study.
(2)A history of hypersensitivity reactions to drugs formulated in polyoxyethylated castor oil.
(3)Having received prior treatment with paclitaxel or cisplatin or carboplatin (other drugs/drug combinations are allowed).
(4)Concomitant treatment with any targeted drug (licensed or experimental) like bevacizumab or cetuximab.
(5)Any condition / concomitant disease not allowing chemotherapy with paclitaxel, the platinum compound (carboplatin or cisplatin) or required premedication for the treatment regimen.
(6)Pregnant/nursing women.
(7)Individuals known to be seropositive for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen or syphilis.
(8)Treatment with cytotoxic or biologic agents or any experimental drug within the 4 weeks prior to beginning treatment on this study.
(9)Secondary malignancy within the last five years, with the exception of adequately treated carcinoma-in-situ of the uterine cervix, basal-cell carcinoma of the skin and pTa or pTis urothelial cancer.
(10)Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.
(11)Preexisting neuropathy > grade I NCI-CTC.

E.5 End points

E.5.1

Primary end point(s)

Frequency of Grade 4 Neutropenia compared between the two treatment arms during the second treatment cycle.

E.5.1.1

Timepoint(s) of evaluation of this end point

Database lock

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Database lock

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3.1

Comparator description

Control Group - standard dosing of Paclitaxel

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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 database will be closed 8 months following the enrollment of the last patient. After completion of the treatment phase, patients will enter into an observational follow-up (F/U) phase until death, lost to follow-up or the overall study end. Therefore, the end of the trial cannot be "last visit of the last subject undergoing the trial".

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1