Clinical Trials Register

Summary
EudraCT Number:	2010-018849-59
Sponsor's Protocol Code Number:	GMIHO-008/2009_AG56
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-01-05
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 - PEI

A.2

EudraCT number

2010-018849-59

A.3

Full title of the trial

A randomized phase II trial of standard carboplatin-based chemotherapy with or without panitumumab in
platinum-sensitive recurrent ovarian cancer

Eine randomisierte Phase II-Studie zu einer Standardkombination mit einer Carboplatin-basierten Chemotherapie mit oder ohne Panitumumab in der Therapie von Patientinnen mit Platin-sensitivem, rezidiviertem Ovarialkarzinom

A.3.1

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

A randomized phase II trial of standard carboplatin-based chemotherapy with or without panitumumab in
platinum-sensitive recurrent ovarian cancer

A.3.2

Name or abbreviated title of the trial where available

PROVE

A.4.1

Sponsor's protocol code number

GMIHO-008/2009_AG56

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	GMIHO Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH
B.1.3.4	Country	Germany
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	AMGEN GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ClinAssess GmbH
B.5.2	Functional name of contact point	CRO
B.5.3	Address:
B.5.3.1	Street Address	Birkenbergstraße 81
B.5.3.2	Town/ city	Leverkusen
B.5.3.3	Post code	51379
B.5.3.4	Country	Germany
B.5.4	Telephone number	492171363360
B.5.5	Fax number	4921713633655
B.5.6	E-mail	info@clinassess.de

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	Vectibix
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B. V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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	PANITUMUMAB
D.3.9.1	CAS number	339177-26-3
D.3.9.4	EV Substance Code	SUB25390
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	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	EGFR-targeted monoclonal antibody

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

Platinum-sensitive recurrent ovarian cancer

E.1.1.1

Medical condition in easily understood language

Platinum-sensitive recurrent ovarian 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	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10033131
E.1.2	Term	Ovarian carcinoma
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

To determine the efficacy of panitumumab plus either the carboplatin/PLD or the carboplatin/gemcitabine combination chemotherapy in k-ras wildtype ovarian cancer patients with platinum-sensitive recurrence, compared to the historical data for the same chemotherapies, which are verified by a randomised control group without the antibody.

E.2.2

Secondary objectives of the trial

Response rate (RR), duration of response (DR), progression-free survival (PFS), overall survival (OS), safety: explorative evaluation in relation to the findings in the reference arm with respect to efficacy and toxicity.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Female patients with pretreated epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer with histological confirmation of the tumor
• Wild-type k-ras status
• Patients must have pretreated platinum-sensitive ovarian cancer with recurrence more than 6 months after completion of a platinum-containing regimen
• Presence of at least one measurable or non-measurable disease (e.g. malignant ascites) following RECIST criteria by radiologic evaluation OR histological confirmation of recurrence by biopsy. The presence of non-measurable lesions only requires in addition a 2-fold increase of CA-125 elevation above normal lab value (confirmed by two measurements).
• No more than 2 prior treatment regimens for these epithelial cancers
• Age ≥ 18 years
• ECOG Performance Status of 0 or 1
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin > 9.0 g/dl
- Leukocyte count >3.000/mm3 ; absolute neutrophil count (ANC) >1.500/mm3
- Platelet count  100.000/μl
- Total bilirubin < 1,0 times the upper limit of normal
- ALT and AST < 2,5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
- Alkaline phosphatase < 4 x ULN
- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
- Serum creatinine < 1.5 x upper limit of normal and creatinine clearance > 50 ml/min.
- Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal
• Signed and dated informed consent before the start of specific protocol procedures.(Analysis of K-RAS mutation status)

E.4

Principal exclusion criteria

• Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment.
• History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan.
• History of HIV infection or chronic hepatitis B or C
• Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
• Pre-existing neuropathy > grade 1 (NCI CTCAE), except for loss of tendon reflex
• Prior radiological or clinical evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by head CT scan or MRI
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
• Patients in a closed institution according to an authority or court decision
• Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
Excluded therapies and medications, previous and concomitant:
• Anticancer chemotherapy within 4 weeks prior to study entry.
• Prior anti-EGFR therapy
• Radiotherapy during study or within 4 weeks of start of study drug. (Palliative radiotherapy of non-target lesions will be allowed) and prior radiotherapy of > 25% of the bone marrow
• Major surgery within 4 weeks of start of study
• Autologous bone marrow transplant or stem cell rescue within 12 months of study
• Investigational drug therapy outside of this trial during or within 4 weeks of study entry
• Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS) rate after 12 months. PFS is defined as the time from randomisation to the time of disease progression or relapse (according to RECIST, not CA-125 only!) or death, or to the date of last tumor assessment without any such event (censored observation).

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after trial inclusion

E.5.2

Secondary end point(s)

Secondary endpoints to be analyzed in both study arms (including
exploratory comparisons) are:
Tumor response rate
Duration of Response
Progression-free survival (PFS)
Overall survival (OS)
Toxicity/safety
alterations in ovarian cancer.

E.5.2.1

Timepoint(s) of evaluation of this end point

Tumor response within treatment
Response duration, PFS, OS on event
Toxicity/safety (with special focus on skin toxicity)

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

E.6.10

Pharmacogenetic

Yes

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

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

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

Standard therapy with Carboplatin and either Doxorubicin PEG-liposomal or Gemcitabin

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

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

Information not present in EudraCT

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

Cf. section 5.11 of the protocol

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.1.1.1

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:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

100

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)

Cf. section 6.4 of the protocol.

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

2011-05-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-11

P. End of Trial
P.	End of Trial Status	Completed

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