Clinical Trials Register

Summary
EudraCT Number:	2005-006173-27
Sponsor's Protocol Code Number:	NV06-0039
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2007-05-30
Trial 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

UK - MHRA

A.2

EudraCT number

2005-006173-27

A.3

Full title of the trial

Multi-Center, Randomized, Double-Blind, Phase III Efficacy Study Comparing Phenoxodiol (Oral Dosage Form) in Combination with Carboplatin versus Carboplatin with Placebo in Patients with Platinum-Resistant or Platinum-Refractory Late-Stage Epithelial Ovarian, Fallopian or Primary Peritoneal Cancer Following at Least Second Line Platinum Therapy

A.3.2

Name or abbreviated title of the trial where available

(OVATURE)

A.4.1

Sponsor's protocol code number

NV06-0039

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Marshall Edwards Pty Limited
B.1.3.4	Country	Australia
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
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	Phenoxodiol
D.3.2	Product code	NV-06
D.3.4	Pharmaceutical form	Capsule*
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Idronoxil
D.3.9.1	CAS number	81267-65-4
D.3.9.2	Current sponsor code	NV-06
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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.IMP: 2
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	Carboplatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Mayne Pharma Plc
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Carboplatin
D.3.2	Product code	Carboplatin
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	Carboplatin
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	10
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule*
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with Platinum-Resistant or Platinum-Refractory, Late-Stage Epithelial Ovarian, Fallopian or Primary Peritoneal Cancer Following at Least Second Line Platinum Therapy

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

E.2.2

Secondary objectives of the trial

To compare the effect of a treatment regimen of (i) daily phenoxodiol in combination with weekly carboplatin, versus (ii) weekly carboplatin therapy in combination with a placebo, on overall survival in patients with platinum-resistant or platinum-refractory, late-stage epithelial ovarian, fallopian or primary peritoneal cancer.

To compare the effect of the treatment regimen on overall response rates, duration of response, clinical status (Karnofsky Performance Score) and quality of life in patients with platinum-resistant or platinum-refractory, late-stage epithelial ovarian, fallopian or primary peritoneal cancer.

Primary safety objectives is:

To compare the effect of the treatment regimen on drug-associated toxicity and intolerance in patients with platinum-resistant or platinum-refractory, late-stage epithelial ovarian, fallopian or primary peritoneal cancer.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Disease type
(a) histologically-confirmed ovarian, fallopian, or primary peritoneal carcinoma of
epithelial origin;
(b) recurrent or persistent advanced disease;
(c) have measurable disease. [Measurable disease being defined as at least one
lesion that can be accurately measured in at least one dimension, allowing a
response to be determined by the RECIST criteria. Each lesion must be ≥ 10 mm
when measured by spiral CT and ≥ 20 mm when measured by conventional CT];

Treatment response history
(d) undergone at least two courses of therapy with a platinum drug (cisplatin or
carboplatin) and have responded to the first of those courses of therapy as
determined by either RECIST or GCIG criteria;
(e) shown disease relapse as determined by either RECIST or GCIG criteria within 6
months of completion of the second or greater course of platinum therapy using a
2- or 3-weekly regimen and
(f) have a platinum-free interval of no greater than 6 months at the time of enrollment, being the time taken from the last day of platinum therapy;

Treatment history
(g) can have any number of previous courses of platinum therapy or non-platinum
therapy;

Clinical status
(h) be considered likely to survive at least 3 months;
(i) have a Karnofsky Performance Score of at least 60%;
(j) have adequate physiological function without evidence of major organ dysfunction
as evidenced by a serum creatinine ≤ 1.5 mg/dl, serum transaminase levels ≤3 x the upper limit of normal (ULN) for the reference laboratory, and a bilirubin level ≤ ULN;
(k) have adequate hematological function defined by platelets > 100,000/ mm3, WCC
> 3,000/mm3, neutrophils > 1,500 /mm3, hemoglobin> 8.0 g/dl;
(l) Have a negative serum pregnancy test (HCG) in patients of childbearing potential

Other
(m)be aged > 18; and
(n) be able to understand the risks and benefits of the study and give written informed consent to participation.

E.4

Principal exclusion criteria

Patients presenting with any of the following will not be included in the study:
a) patients with mucinous histological type of ovarian cancer;
b) patients who have failed to show a clinical response (RECIST or GCIG criteria) to
at least one prior course of platinum therapy;
c) patients with active infection;
d) patients with concurrent severe and/or uncontrolled medical disease (e.g.,
uncontrolled diabetes, hypertension, ischemic heart disease, congestive heart
failure, etc.);
e) patients with a history of chronic active hepatitis or cirrhosis;
f) patients with HIV;
g) patients with active CNS metastases. Patients with known CNS metastases must
have received prior radiation therapy, and CNS metastatic disease must be stable
for 4 weeks;
h) patients who have not recovered from the acute effects of any prior anti-neoplastic therapy; and
i) patients with known hypersensitivity to platinum drugs that cannot be managed with concomitant medication.

E.5 End points

E.5.1

Primary end point(s)

Primary efficacy end-point:
Progression-Free Survival (PFS)- defined as the time from randomization until objective tumor progression or death. PFS will be determined by measuring the time (in weeks) from randomization until the patient’s disease has progressed according to RECIST criteria, or in the event of death without disease progression.

Secondary end-point
Overall Survival (OS): defined as the time from randomization until death from any cause.

Tertiary end-points:
Overall Response Rate (ORR): defined as the incidence within either of the two treatment groups of patients showing a reduction in tumor burden as determined according to RECIST criteria. ORR is the number of subjects in each treatment group with complete or partial response.
Duration of Response: defined as the time from response (according to standard RECIST criteria) until disease progression (according to standard RECIST criteria) and will be measured in weeks.
Clinical Status: determined on the basis of Karnofsky Performance Score for each patient measured at baseline, at the conclusion of each treatment cycle, at the end of treatment, and again at the end of study (4 weeks post completion of treatment).
Quality of Life: determined on the basis of QOL FACT-O and FACT-BRM questionnaires for each patient measured at baseline, at the conclusion of every 2 treatment cycles and at the end of treatment.

Safety endpoints are: adverse events, physical and neurological examinations, ECG's, serum chemistry and hematology and coagulation studies.

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

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3

Other

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

Yes

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

last visit of the last patient

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	100
F.4.2	For a multinational trial
F.4.2.1	In the EEA	280
F.4.2.2	In the whole clinical trial	340

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

2007-07-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2007-08-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-01-31

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