Clinical Trials Register

Summary
EudraCT Number:	2012-003810-15
Sponsor's Protocol Code Number:	PazoDoble
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-07-23
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

Germany - BfArM

A.2

EudraCT number

2012-003810-15

A.3

Full title of the trial

Pazopanib versus Pazopanib plus Gemcitabine in patients with relapsed or metastatic uterine leiomyosarcomas or other uterine tumour: a multi-center, randomized phase-II clinical trial of the NOGGO and AGO

Pazopanib versus Pazopanib plus Gemcitabin in Patientinnen mit rezidiviertem oder metastasiertem uterinem Leiomyosarkom oder einem anderen uterinen Tumor:
eine multizentrische, randomisierte klinische Prüfung der Phase II der NOGGO und der AGO

A.3.1

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

Pazopanib versus Pazopanib plus Gemcitabine in patients with relapsed or metastatic uterine leiomyosarcomas or other uterine tumour

Pazopanib versus Pazopanib plus Gemcitabin in Patientinnen mit rezidiviertem oder metastasiertem uterinem Leiomyosarkom oder einem anderen uterinen Tumor

A.3.2

Name or abbreviated title of the trial where available

PazoDoble

A.4.1

Sponsor's protocol code number

PazoDoble

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	NOGGO e.V.
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
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	Yes
D.2.1.1.1	Trade name	Gemedac
D.2.1.1.2	Name of the Marketing Authorisation holder	medac Gesellschaft für klinische Spezialpräparate mbH
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	Gemedac
D.3.4	Pharmaceutical form	Powder 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	Gemcitabine
D.3.9.3	Other descriptive name	GEMCITABINE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB02324MIG
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	38
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.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	Votrient 200 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Group Limited
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.3.1	Product name	Pazopanib
D.3.2	Product code	GW786034
D.3.4	Pharmaceutical form	Coated tablet
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	PAZOPANIB HYDROCHLORIDE
D.3.9.1	CAS number	635702-64-6
D.3.9.4	EV Substance Code	SUB31270
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)	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.IMP: 3
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	Votrient 400 mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Group Limited
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.3.1	Product name	Pazopanib
D.3.2	Product code	GW786034
D.3.4	Pharmaceutical form	Coated tablet
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	PAZOPANIB HYDROCHLORIDE
D.3.9.1	CAS number	635702-64-6
D.3.9.4	EV Substance Code	SUB31270
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	400
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

This study is a prospective, randomized, open-label, multicenter phase II trial in order to determine progression-free survival of patients with refractory or relapsed metastatic uterine leiomyosarcomas or other metastatic uterine tumours treated with Pazopanib plus Gemcitabine or Pazopanib alone.

E.1.1.1

Medical condition in easily understood language

Metastatic uterine uterine tumours treated with Pazopanib plus Gemcitabine or Pazopanib alone will be analysed concerning progression-free survival.

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

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	10007508
E.1.2	Term	Carcinosarcoma uterus
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10046799
E.1.2	Term	Uterine leiomyosarcoma
E.1.2	System Organ Class	10029104 - 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

• 6 months progression free survival assessed as rate of patients without progression after 6 months
• Second malignancy or clinical progression - patients with unknown or missing PFS at 6 months will be treated as non-responder

E.2.2

Secondary objectives of the trial

• Objective response rate (RECIST v1.1 criteria)
• Duration of response defined as the time in months from first assessment of CR or PR until the first date of PD or death
• Time to progression (TTP) of a patient being defined as the time in months from start of the first therapy cycle until PD is observed
• Overall survival (OS) calculated from the day of study enrolment until the day of death.
• Progression-free survival (PFS) calculated from the day of study enrolment until the day of progression/death
• Toxicity and tolerability
• Quality of life (EORTC QLQ-C30)
• Translational research within a tumour bank

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects must provide informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up. Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
2. Histologically or cytological confirmed uterine leiomyosarcoma or uterine carcinosarcoma including any subtypes
3. Patient must have received one or two prior chemotherapies
4. For patients with prior anthracycline therapy normal cardiac function with LVEF at least 50% must be assessed by quantitative echocardiogram or MUGA scan
5. Prior Gemcitabine containing chemotherapy is permitted provided that at least 8 weeks have elapsed since the last dose of therapy
6. ECOG performance status 0-1
7. At least 18 years old
8. Measurable disease according to RECIST v 1.1 criteria (in case of tumour debulking - staging CT-scan after surgery)
9. Able to swallow and retain oral medication
10. Adequate organ system function
11. Non-childbearing potential or negative serum pregnancy test of women of childbearing potential

E.4

Principal exclusion criteria

1. Prior malignancy except disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
2. Prior treatment with any anti-angiogenic agent including bevacizumab and tyrosine kinase inhibitors
3. Active malignancy or any malignancy in the last 5 years prior to first dose of study drug other than LMS and CS
4. History or clinical evidence of central nervous system (CNS) or leptomeningeal metastases, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
5. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
• Grade 3/4 diarrhea
6. Corrected QT interval (QTc) > 480 msecs using Barzett’s formula
7. History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg].
8. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
9. Major surgery or trauma within 28 days prior to study enrolment or any non- healing wound, fracture or ulcer (procedures such as catheter placement not considered to be major)
10. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Pazopanib or Gemcitabine
11. Evidence of active bleeding or bleeding diathesis
12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
13. Hemoptysis in excess of 2.5 mL(or one half teaspoon) within 8 weeks prior to the first dose of study drug
14. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures
15. Unable or unwilling to discontinue use of prohibited medications listed in the study protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
16. Treatment with any of the following anti-cancer therapies
- Radiation therapy, surgery or tumour embolization within 14 days prior to the first dose of study drug
- Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug
17. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia
18. Pregnancy (for women of childbearing potential to be confirmed by negative serum pregnancy test) or lactation period
Women of childbearing potential:
missing contraception (Pearl-Index <1, e.g. hormonal contraception including the combined oral contraceptive pill, the transdermal patch, and the contraceptive vaginal ring, intrauterine devices or sterilization) for 14 days before exposure to investigational product, during study treatment and for at least 6 months thereafter
19. Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
20. Legal incapacity or limited legal capacity
21. Participation in another clinical study with experimental therapy within 30 days prior to study enrolment

E.5 End points

E.5.1

Primary end point(s)

Progression free survival (PFS) of Pazopanib plus Gemcitabine and of Pazopanib as a single agent in patients with leiomysarcoma according to RECIST v1.1 criteria assessed as rate of patients without progression at 6 months after study enrolment.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months after study enrolment

E.5.2

Secondary end point(s)

• Response rate (RECIST v1.1 criteria), i.e. percentage of patients showing overall response (CR+PR), progression or stable disease
• Duration of response defined the time in months from first assessment of CR or PR until the first date of PD or death
• Time to progression (TTP) of a patient being defined as the time in months from start of the first therapy cycle until PD is observed
• Overall survival (OS) calculated from the day of study enrolment until the day of death. The median survival is calculated using the Kaplan-Meier method and a 95% confidence interval will be reported.
• Progression-free survival (PFS) calculated from the day of study enrolment until the day of progression/death
• Toxicity and tolerability
• Assessment of Quality of life over time as defined by EORTC-QLQ C 30 questionnaire
• Translational research within the tumour bank

E.5.2.1

Timepoint(s) of evaluation of this end point

• Response rate:
6 + 12 weeks after start of treatment
6, 9 and 12 months after start of treatment
Thereafter every 6 months until PD (and any other time with an indication of a change in disease status).
• Duration of response: time in months from first assessment of CR or PR until the first date of PD or death
• Time to progression (TTP): from start of the first therapy cycle until PD is observed
• Overall survival (OS): day of death.
• Progression-free survival (PFS): day of study enrolment until the day of progression/death
• Toxicity and tolerability during the whole study
• Quality of life: before every treatment cycle + end of treatment, thereafter every 3 months
• Translational research within the tumour bank: at the beginning of the 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

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

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

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

Pazopanib alone

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

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

LVLS

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

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

107

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)

Following the end of treatment evaluation or the end of treatment for any other cause, patients will be treated and followed according to the guidelines of the German Cancer Society.

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

2013-08-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-12-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2024-02-14

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