Study to investigate the combination of Lanreotide Autogel 120mg and Temozolomid in patients with WITH PROGRESSIVE GASTRO-ENTERO-PANCREATIC NEUROENDOCRINE TUMOURS

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2013-001697-17-AT
• Date of registration: 22/04/2014
• Prospective Registration: Yes
• Primary sponsor: Ipsen Pharma GmbH
• Public title: Study to investigate the combination of Lanreotide Autogel 120mg and Temozolomid in patients with WITH PROGRESSIVE GASTRO-ENTERO-PANCREATIC NEUROENDOCRINE TUMOURS
• Scientific title: PHASE II, MULTICENTRE, OPEN LABEL STUDY TO EVALUATE THE EFFICACY OF THE COMBINATION OF LANREOTIDE AUTOGEL 120 MG AND TEMOZOLOMIDE IN PATIENTS WITH PROGRESSIVE GASTRO-ENTERO-PANCREATIC NEUROENDOCRINE TUMOURS (GEP-NET) G1/G2 - A PILOT-STUDY - SONNET
• Date of first enrolment: 23/05/2014
• Target sample size: 65
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001697-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany

Contacts

• Name: Philipp Hoffmanns
• Affiliation: Ipsen Pharma GmbH

• Name: Philipp Hoffmanns
• Affiliation: Ipsen Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
(1)Provision of written informed consent prior to any study related procedures.
(2)Male or female of 18 years of age or older.
(3)Inoperable, Gastro-Entero-Pancreatic-Neuroendocrine Tumour G1 or G2 (Ki67-Index: 0 to =20%) confirmed by pathological/histological assessment.
(Previous data assessed not longer than 24 months ago could be used.)
(4)Progressive disease within 12 months before inclusion (RECIST 1.1: increase of >20% tumour load; by CT or MRI).
(5)Metastatic disease confirmed by CT/MRI.
(6)Measureable disease according to RECIST 1.1.
(7)Functioning or non-functioning NET (G1, G2).
(8)WHO performance status 0-2.
(9)Positive Octreo-Scan (= grade 2 Krenning scale) or positive DOTA-TATE/TOC-PET-CT within 12 months prior to screening.
(10)Absolute neutrophile count (ANC) = 1,5x10E09/l prior to Temozolomide intake, thrombocyte count = 100 x 10 E09/l prior to Temozolomide intake.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
(1)Has the diagnosis of Insulinoma
(2)Has a history of hypersensitivity to Lanreotide or Temozolomide or drugs with a similar chemical structure and/or any known contraindications to magnetic resonance imaging (MRI)/computerised tomography (CT).
(3)Was treated with any other IMP within the last 30 days before screening visit.
(4)Is likely to require treatment during the study with drugs that are not permitted by the study protocol.
(5)Is at risk of pregnancy or lactation. Females of childbearing potential must provide a negative pregnancy test at start of study and must be using oral, double barrier or injectable contraception. Non childbearing potential is defined as post-menopausal for at least 2 years, surgical sterilisation or hysterectomy at least three months before the start of the study (according to CPMP/ICH/286/95, modified).
(6)Male patients, who do not agree to use an effective method of contraception if their partner is at risk of becoming pregnant during the course of this study and 6 months after the study drug administration.
(7)Male patients who are planning a sperm donation during the entire study participation and at least six months after the last study drug administration.
(8)Has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
(9)Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient’s safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.
(10)HbA1c > 8,5% (centrally assessed during the screening period).
(11)Has had major surgery related to the studied disease within 3 months prior to screening visit.
(12)Has a diagnosis of a multiple endocrine neoplasia (MEN).
(13)Has received Sunitinib, Everolimus within the last 4 weeks prior to screening visit.
(14)Has received PRRT (Peptide Radio-Receptor-Therapy) within 3 months prior to screening visit.
(15)Has received prior chemotherapy regimens within 4 weeks prior to screening visit.
(16)Has received any Temozolomide treatment prior to screening visit.
(17)Has undergone radiation of target lesions within 12 months prior to screening visit.
(18)Has received Interferon-a treatment within 4 weeks prior to screening visit.
(19)Has received local ablative therapies (TACE, SIRT, RFA) within 6 months prior to screening visit.
(20)Has had a previous cancer (except basocellular carcinoma of the skin and/or in situ carcinoma of the cervix/uterus and/or patients treated with curative intent and free from disease for more than 5 years) other than study indication.
(21)Has a history of, or known current, problems with alcohol or drug abuse.
(22)Is deprived of his/her freedom or rights by virtue of an order issued either by any judicial or administrative authorities, is unable to express his/her consent, or is committed to a social or health institution for reasons other than the study.
(23)Has been previously enrolled in this study.
(24)Participation in other trials for the duration of this trial.
(25)Hypersensitivity to dacarbazine (DTIC).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

metastatic functioning and non-functioning entero-pancreatic tumours

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: Somatuline Autogel 120 mg
Pharmaceutical Form: Solution for injection
INN or Proposed INN: LANREOTIDE
CAS Number: 108736-35-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-

Trade Name: Temozolomide SUN 5mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Temozolomide SUN 20mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Temozolomide SUN 100mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Temozolomide SUN 250mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Temozolomide SUN 5mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Temozolomide SUN 20mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Temozolomide SUN 100mg Hartkapseln
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Temozolomide
Other descriptive name: TEMOZOLOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Temozolomide SUN 250mg Hartkapseln
Pharmaceutical Form: Capsule, hard

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: please see section E.5.1 above

Primary end point(s): Disease control rate (Complete response + partial response + stable disease; measured by RECIST 1.1, centrally assessed) after 6 months of combination treatment

Secondary Objective: •To evaluate the efficacy (disease control rate) after 12 months
•To evaluate time to (objective) response
•To evaluate duration of (objective) response
•To evaluate biochemical response (CgA, 5-HIAA)
•To evaluate symptomatic response (where appropriate)
•To estimate progression-free survival
•To assess safety (CTCAE version 4.0)
•To assess changes in quality of life (EORTC QLQ-C30+ GI.NET21)
•To evaluate response in correlation to MGMT expression
•To evaluate if combination with Temozolomide has an impact on Lanreotide ATG 120 mg plasma levels
•To evaluate somatostatin receptor expression

Main Objective: The primary study objective is to evaluate the efficacy of Lanreotide Autogel (ATG) 120 mg in combination with Temozolomide in patients with functioning as well as non-functioning, progressive, gastro-entero-pancreatic NET G1 or G2.

Secondary Outcome(s)

Secondary end point(s): •Disease control rate (Complete response + partial response + stable disease; measured by RECIST 1.1, centrally assessed) after 12 months (6 months combination treatment followed by either 6 months Lanreotide ATG 120 mg maintenance or 6 months wait and see)
•Time to progression or death occurring within 12 months after first combination treatment (statistical estimation of progression-free survival (PFS))
•Time to response (Complete response + partial response ) within the study period of 12 months
•Duration of response (Complete response + partial response ) within the study period of 12 months
•Biochemical response after 6 months and after 12 months
-Percentage of patients with normalized and percentage of patients with stabilized CgA-levels defined as <50% increase of CgA level compared to baseline
-Percentage of CgA reduction (>/= 50%) compared to baseline
-5-HIAA reduction (5-HIAA only in carcinoids) compared to baseline
• Symptomatic response (where appropriate) after 6 months and after 12 months
-Changes in the frequency of the symptomatic episodes (target symptoms: diarrhoea, flush) (the mean of the last 3 days) that could be experienced by a patient as compared to baseline.
• QoL questionnaire (QLQ-30+ G.I.NET 21):
-changes from baseline in quality of life over 6 month
-changes from 6 months to 12 months after further 6 months Lanreotide ATG maintenance treatment by means
•AEs (by CTCAE v 4.0) will be recorded for each patient throughout the study
•Vital signs at V1 to V8, V11 and V14 , and physical examination at V1, V3, V5, V8, V11 and V14
•ECG at V1, V5, V8 and V14
•Gallbladder ultrasound baseline, 6 months and 12 months
•Laboratory tests: standard haematology and biochemistry
analyses (V1, V3-8, V11, V14 or withdrawal visit)
•Lanreotide plasma levels at baseline, 4 weeks, 3 months, 6 months, 12 months
•MGMT expression and methylation correlated to tumour response
•MGMT expression measured by immunohistochemistry and MGMT methylation measured by polymerase chain reaction (PCR)
-Quantitative analysis of somatostatin receptor (SSTR) correlated to tumour response

Timepoint(s) of evaluation of this end point: please see section E.5.2 above

Secondary ID(s)

A-94-52030-268

Source(s) of Monetary Support

Ipsen Pharma GmbH