A study to investigate the efficacy of ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic neuroendocrine tumors of the pancreas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Martin-Luther-Universitaet Halle-Wittenberg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Apr 2018 → 6 Jun 2025

Decision date (initial)

2024-10-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515045-42-00

EudraCT number

2017-001207-68

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The aim of this study is to investigate whether ramucirumab in combination with dacarbacine has an effect on the disease-control in patients with progressive pancreatic neuroendocrine tumors

Secondary objectives 1

1. Secondary aims are to investigate the tumor response, survival, progression-free survival, the toxicity profile of the combination therapy, the biochemical response and Quality of Life. Additionally a translational research aims to investigate predictive biomarkers.

Conditions and MedDRA coding

Progressive well-differentiated metastatic neuroendocrine tumors of the pancreas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Histologically confirmed unresectable metastatic G1-G2 differentiated pancreatic neuroendocrine tumor (non-functional and functional NET) excluding neuroendocrine carcinomas - Age: 18-75 years - Measurable disease (RECIST 1.1) - Progressive disease under treatment with either non-DTIC-based chemotherapy, SSA analogues, everolimus or sunitinib. No prior therapy with DTIC or temozolomide. Prior TACE and SIRT allowed with a minimum of 3 months before study entry, prior PRRT with a minimum of 12 months before study entry - ECOG 0-1 - Life expectancy > 12 weeks - Adequate renal, hepatic, bone marrow and coagulation function - Sexually active patiens: postmenopausal, surgically sterile, or use of effective contraception (Pearl Index <1). Female patients of childbearing potential: negative serum pregnancy test within 7 days prior to first dose of protocol therapy. - Written informed consent

Exclusion criteria 1

1. - Pregnancy or lactation. - Secondary malignancy in patient's history with the exception of: disease-free period > 5 years before randomization or non-melanoma skin cancer or curatively treated cervical carcinoma in situ or other noninvasive in situ neoplasm. - Allergy against dacarbazine or ramucirumab - Current enrolment or participation within the last 4 weeks in a clinical drug trial - Any arterial thromboembolic events within 6 months prior to first dose of protocol therapy. Insufficient liver function - Uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management - Chronic antiplatelet therapy, once-daily aspirin use (maximum dose 325 mg/day) permitted - Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy. - History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy - Uncontrolled severe physical or mental disorders - Pathological condition present that carries a high risk of bleeding - History of gastrointestinal perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation. - Major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy. Elective or planned major surgery to be performed during the course of the clinical trial. - Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy. - officially and/or legally accomodated persons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease control rate (DCR) after 6 months from study entry, determined according to RECIST 1.1 or death

Secondary endpoints 1

1. - Objective tumor response (ORR) - progression-free survival (PFS) - overall survival (OS) - toxicity - biochemical response (tumor marker chromogranin A; in cases of functional NET: gastrin, insulin) - Quality of Life (EORTC QLQ-C30 questionnaire) Translational research: - Predictive biomarkers (circulating VEGF, ANGPT1/2 and IL8 levels, immunohistochemical VEGFR2 expression)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Martin-Luther-Universitaet Halle-Wittenberg

Sponsor organisation

Martin-Luther-Universitaet Halle-Wittenberg

Address

Ernst-Grube-Strasse 40, Kroellwitz Kroellwitz

City

Halle (Saale)

Postcode

06120

Country

Germany

Scientific contact point

Organisation

Martin-Luther-Universitaet Halle-Wittenberg

Contact name

Prof. Dr. med. Patrick Michl

Public contact point

Organisation

Martin-Luther-Universitaet Halle-Wittenberg

Contact name

Prof. Dr. med. Patrick Michl

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications