Clinical trial • Phase II • Oncology

Cabozantinib for Neuroendocrine neoplasia | Neuroendocrine tumor

Phase II trial of Cabozantinib for Neuroendocrine neoplasia | Neuroendocrine tumor. None/Not specified-controlled. 45 participants.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Neuroendocrine neoplasia | Neuroendocrine tumor
Trial Stage
Phase II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
31-07-2024
First CTIS Authorization Date
30-08-2024

Trial design

None/Not specified-controlled Phase II trial across 12 sites in Germany, Austria.

Comparator
None/Not specified
Target Sample Size
45

Eligibility

Recruits 45 No vulnerable population selected (isVulnerablePopulationSelected: false). Patients without legal capacity are explicitly excluded: "Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial". Written informed consent is required: "Written informed consent obtained according to international guidelines and local laws"; participants must be able to understand and comply with trial procedures. Minors are excluded by age criterion (aged ≥ 18 years)..

Pregnancy Exclusion
Current or planned pregnancy, nursing period
Vulnerable Population
No vulnerable population selected (isVulnerablePopulationSelected: false). Patients without legal capacity are explicitly excluded: "Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial". Written informed consent is required: "Written informed consent obtained according to international guidelines and local laws"; participants must be able to understand and comply with trial procedures. Minors are excluded by age criterion (aged ≥ 18 years).

Inclusion criteria

  • {"criterion_text":"- Patients with histologically confirmed diagnosis of neuroendocrine neoplasia\n- Tumor proliferation rate has to be > Ki67 20% and ≤ Ki67 60% (local assessment)\n- Male, female, or diverse patients aged ≥ 18 years without upper age limit\n- Patients with upto four different antitumoral therapies\n- At least one measurable tumor lesion in CT or MRI scan\n- Newly diagnosed or progressive disease assessed per RECIST criteria 1.1\n- Patients must have a performance status of ECOG 0-2\n- Patients must have a life expectancy of more than 3 months\n- Hb> 9 g/dl\n- Platelets >80T/µl\n- White blood cells >3T/μL\n- Total bilirubin <3mg/dl\n- AST and ALT <4xN\n- Serum creatinine <2mg/dl, eGFR >40mL/min/1.73m2\n- BUN <5xN\n- Lipase <3xN\n- Albumin ≥2.8 g/dL\n- PT/PTT ≤ 1.5 × ULN\n- Urine protein:creatinine ration ≤ 1 (Note: if proteinuria < 2g/l and increased proteinuria is ruled out by an urine teststick the protein:creatinine ratio does not need to be determined)\n- Written informed consent obtained according to international guidelines and local laws\n- Ability to understand the nature of the trial and the trial related procedures and to comply with them"}

Exclusion criteria

  • {"criterion_text":"- Patients with Mixed Neuroendocrine-Non-neuroendocrine Neoplasia (MINEN)\n- Patients with former treatment with TKI or VEGF receptor antagonist\n- Patients with additional malignancy <5 years in medical history (exclusion: non-invasive skin cancer)\n- Patients with symptomatic brain metastases\n- Patients with known HIV infection, acute and chronic-active hepatitis (type A, B or C) or another uncontrolled infection\n- Patients with known hypersensitivity to Cabozantinib or contraindications for treatment with Cabozantinib according to Summary of Product Characteristics (SmPC)\n- Patients with class III or IV congestive heart failure\n- Patients with prolonged QTc (for woman more than 470 ms, for men 450 ms)\n- Patients with uncontrolled hypertension (despite anti-hypertensive medication RR:>160/110 mmHg)\n- Patients with severely impaired lung function\n- Patients with history of organ transplant (exclusion: cornea transplantation)\n- Patients with clinical apparent acute or chronic gastric ulceration\n- Patients with history of hemophilia\n- Patients with surgery at the GI tract within the last 12 weeks\n- Patients with uncontrolled inflammatory bowel disease\n- Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed\n- Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial\n- Previous participation in this trial\n- Concomitant use of therapeutic anticoagulation or strong CYP3A4 inducers or inhibitors (e.g. amiodarone)\n- Known or persistent abuse of medication, drugs or alcohol\n- Person who is in a relationship of dependence/employment with the sponsor or the investigator\n- Current or planned pregnancy, nursing period"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Disease control rate (DCR) 6 months after treatment start (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD))","definition_or_measurement_approach":"DCR at 6 months after treatment start defined as CR + PR + SD (measured per RECIST criteria 1.1 as implied elsewhere in the protocol)"}

Secondary endpoints

  • {"endpoint_text":"- Disease control rate 3 and 12 months after treatment start","definition_or_measurement_approach":"DCR at 3 and 12 months after treatment start (CR + PR + SD), assessed over specified timepoints"}
  • {"endpoint_text":"- Objective response rate (ORR) 3 months after treatment start and best objective response rate","definition_or_measurement_approach":"ORR at 3 months and best overall response (likely assessed per RECIST 1.1)"}
  • {"endpoint_text":"- Progression free survival (PFS) and overall survival (OS)","definition_or_measurement_approach":"Time-to-event endpoints; PFS and OS measured using standard survival analysis methods (dates of progression and death)"}
  • {"endpoint_text":"- Time on drug (TOD)","definition_or_measurement_approach":"Duration on study drug (from treatment start to discontinuation)"}
  • {"endpoint_text":"- EORTC QLQ-C30 Quality of Life Questionnaire monthly for 12 months after treatment start and after 15 months","definition_or_measurement_approach":"QoL assessed with EORTC QLQ-C30 monthly for 12 months and at 15 months"}
  • {"endpoint_text":"- Serious adverse events and adverse events, Data Safety Monitoring Board (DSMB)","definition_or_measurement_approach":"Safety endpoints: collection and reporting of adverse events and serious adverse events; oversight by DSMB"}

Recruitment

Planned Sample Size
45
Recruitment Window Months
51
Consent Approach
Written informed consent obtained according to international guidelines and local laws; adults (≥18 years) provide consent. Subject information and informed consent form documents are available (e.g. 'L1 PIC_G_for pub', 'L1_CABONEN_PIC_A_for pub' and pregnancy parts 'L1 PICpregPart_G_for pub', 'L1_CABONEN_PICpregPart_A_for pub'). No assent process described (minors excluded).

Geography

Total Number Of Sites
12
Total Number Of Participants
45

Germany

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
30-08-2024
Processing Time Days
8
Number Of Sites
11
Number Of Participants
40

Sites

Site Name
Zentralklinik Bad Berka GmbH
Department Name
Klinik für Innere Medizin/Gastroenterologie und Endokrinologie
Contact Person Name
Dieter Hörsch
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
Contact Person Name
Thomas Wirth
Contact Person Email
Wirth.Thomas@mh-hannover.de
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Medizinische Klinik I
Contact Person Name
Marianne Pavel
Contact Person Email
marianne.pavel@uk-erlangen.de
Site Name
Universitaetsklinikum Wuerzburg AöR
Department Name
ENET, Medizinische Klinik II, Gastroenterologie
Contact Person Name
Alexander Weich
Contact Person Email
weich_a@ukw.de
Site Name
Medical Center - University Of Freiburg
Department Name
Gastroenterologie, Endokrinologie, Stoffwechsel und klinische Infektiologie
Contact Person Name
Michael Quante
Site Name
Philipps-Universitaet Marburg
Department Name
Gastroenterologie, Endokrinologie, Stoffwechsel und klinische Infektiologie
Contact Person Name
Anja Rinke
Contact Person Email
gastro@med.uni-marburg.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Klinik für Medizinische Onkologie
Contact Person Name
Leonidas Apostolidis
Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik I
Contact Person Name
Anke Kröcher
Contact Person Email
oncostudy@ukdd.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie
Contact Person Name
Alexander König
Site Name
Universitaetsklinikum Halle (Saale) AöR
Department Name
Klinik für Innere Medizin I, (Gastroenterologie, Pneumologie)
Contact Person Name
Jonas Rosendahl
Contact Person Email
jonas.rosendahl@uk-halle.de
Site Name
Universitaetsklinikum Mannheim GmbH
Department Name
Gastroenterologie, Hepatologie, Infektiologie, Ernährungsmedizin
Contact Person Name
Nadine Schulte
Contact Person Email
nadine.schulte@umm.de

Austria

Earliest CTIS Part Ii Submission Date
22-08-2024
Latest Decision Or Authorization Date
02-09-2024
Processing Time Days
11
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Universitaet Wien
Department Name
Universitätsklinik f. Innere Medizin I
Contact Person Name
Markus Raderer

Sponsor

Primary sponsor

Full Name
Universitaetsmedizin Goettingen
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Germany

Investigational products

Investigational Product Name
CABOMETYX 20 mg film-coated tablets
Active Substance
Cabozantinib
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation present (EU marketing authorisation number listed)
Dose Levels
20 mg
Maximum Dose
20 mg
Investigational Product Name
CABOMETYX 40 mg film-coated tablets
Active Substance
Cabozantinib
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation present (EU marketing authorisation number listed)
Dose Levels
40 mg
Maximum Dose
40 mg
Investigational Product Name
CABOMETYX 60 mg film-coated tablets
Active Substance
Cabozantinib
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation present (EU marketing authorisation number listed)
Dose Levels
60 mg
Maximum Dose
60 mg

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