Clinical Trials Register

Summary
EudraCT Number:	2016-003599-39
Sponsor's Protocol Code Number:	SAKK08/15
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-12-14
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

France - ANSM

A.2

EudraCT number

2016-003599-39

A.3

Full title of the trial

PROMET - Multicenter, Randomized Phase II Trial of Salvage Radiotherapy +/- Metformin for Patients with Prostate Cancer after Prostatectomy

Etude de phase II, randomisée, multicentrique de radiothérapie de rattrapage en association avec la metformine chez des patients atteints d’un cancer de la prostate après prostatectomie

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

PROMET

A.4.1

Sponsor's protocol code number

SAKK08/15

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	SAKK - SWISS GROUP FOR CLINICAL CANCER RESEARCH
B.1.3.4	Country	Switzerland
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	Werner und Hedy Berger-Janser Stiftung zur Erforschung der Krebskrankheiten, Bernische Krebsliga, Rising Tide Foundation
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Krebsforschung Schweiz
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	State Secretariat for Education, Research and Innovation (SERI)
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Swiss Cancer Research Foundation and Swiss Cancer League
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	UNICANCER
B.5.2	Functional name of contact point	Soazig Nénan
B.5.3	Address:
B.5.3.1	Street Address	101 rue de Tolbiac
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75654 cedex 13
B.5.3.4	Country	France
B.5.4	Telephone number	+331 85 34 31 13
B.5.5	Fax number	+331 85 34 33 79
B.5.6	E-mail	s-nenan@unicancer.fr

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	Glucophage
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK
D.2.1.2	Country which granted the Marketing Authorisation	France
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
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	METFORMIN
D.3.9.1	CAS number	657-24-9
D.3.9.4	EV Substance Code	SUB08831MIG
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	662,90
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

Adenocarcinoma of the prostate after Prostatectomy

E.1.1.1

Medical condition in easily understood language

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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 main objective of the trial is to determine if SRT plus metformin is superior to SRT alone in the endpoint of time to progression after prostatectomy failure.

E.2.2

Secondary objectives of the trial

Investigate the presence and magnitude of a potential association between metabolic syndrome components, disease aggressiveness and clinical endpoints

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
2. Histologically confirmed adenocarcinoma of the prostate without small cell features
3. Tumor stage pT2a-3b, pN0 or cN0, M0, R0-1 resection margins, according to UICC TNM 2009 (see Appendix 1), Gleason score available
4. Radical prostatectomy (RP) at least 12 weeks before registration
5. PSA progression after RP defined as two consecutive rises with the final PSA > 0.1 ng/mL or three consecutive rises. The first value must be measured earliest 4 weeks after RP
6. PSA ≤ 2 ng/mL within 14 days prior to registration
7. Age ≥ 18 years at time of registration
8. WHO performance status 0-1 (see Appendix 2)
9. Adequate hepatic function within 14 days prior to registration: bilirubin ≤ 1.5 x ULN (exception if Gilbert’s syndrome ≤ 3 x ULN), AST and ALT ≤ 2.5 x ULN
10. Adequate renal function within 14 days prior to registration: calculated corrected creatinine clearance ≥ 60 mL/min, according to the formula of corrected Cockcroft-Gault (see Appendix 3)
11. Patient agrees not to father a child during salvage radiotherapy and during 6 months thereafter
12. Paraffin block of the surgical specimen containing representative tumor tissue and non-neoplastic prostatic tissue available for biobanking (see section 17).

E.4

Principal exclusion criteria

1. Persistent PSA (> 0.4 ng/mL) 4 to 20 weeks after RP
2. Pelvic lymph node enlargement > 0.8 cm in short axis diameter (cN positive) assessed by mpMRI within 12 weeks prior to registration, unless the enlarged lymph node is sampled and negative
3. Evidence of macroscopic local recurrence assessed by mpMRI within 12 weeks prior to registration as described in Appendix 6
4. Palpable prostatic fossa mass suggestive of recurrence, unless an ultrasound guided biopsy is negative for malignancy
5. Presence or history of prostate cancer metastases. In case of clinical suspicion (e.g. bone pain), imaging (e.g. bone scan, Cholin-PET, PSMA-PET, whole body MRI) must be performed. The imaging method is at the discretion of the investigator
6. Previous hematologic or primary solid malignancy within 3 years prior registration with the exception of curatively treated localized non-melanoma skin cancer
7. Patients on pharmacotherapy for diabetes mellitus
8. Treatment with metformin within the last 3 months prior to registration
9. Prior pelvic radiotherapy
10. Hormonal treatment in the form of bilateral orchiectomy prior or following RP
11. Usage of products known to affect PSA levels within 4 weeks prior to start of trial treatment (see Appendix 4)
12. Bilateral hip prosthesis
13. Severe or active co-morbidity likely to impact on the advisability of salvage RT, e.g.:
a. History of inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
b. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
c. Unstable angina, myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months
d. Transmural myocardial infarction within the last 6 months
e. Chronic obstructive pulmonary disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
14. Any condition associated with increased risk of lactic acidosis (e.g. alcohol abuse, congestive heart failure NYHA III or IV [see Appendix 5])
15. Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including viral or hepatitis, current alcohol abuse, or cirrhosis for use with metformin according to the approved product information
16. Any acute or chronic condition that could cause tissue hypoxia (e.g. cardiac or respiratory insufficiency, shock)
17. Treatment with any experimental drug or participation within a clinical trial within 30 days prior to registration (exception: concurrent participation in the biobank study SAKK 63/12 is allowed)
18. Any concomitant drug contraindicated for use with metformin according to the approved product information
19. Known hypersensitivity to metformin or to any of its components
20. Inability or unwillingness to swallow oral medication
21. Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the trial is time to progression, defined as time from randomization until one of the following events, whichever comes first:
- Biochemical progression
- Clinical progression
- Death due to clinical progression
Patients not experiencing an event will be censored at the date of the last available assessment. Patients starting further anti-cancer systemic treatment (e.g. hormonal therapy) before experiencing an event will be censored at the date of the last available assessment before the start of further anti-cancer systemic treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

Secondary endpoints of the trial are:
- Progression-free survival (PFS)
- Undetectable PSA under normal testosterone levels
- 50% PSA response
- Clinical progression-free survival
- Time to further anti-cancer systemic therapy
- Prostate cancer-specific survival (PCSS)
- Overall survival (OS)
- Adverse events (AE)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

E.8.9.2

In all countries concerned by the trial years

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

170

F.4.2.2

In the whole clinical trial

170

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)

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

2017-12-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-11-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-02-28

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