Study evaluating thromboprophylaxis in patients with advanced germ cell tumours of good or intermediate prognosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Neoplasms [C04]

Trial duration

17 Oct 2023 → ongoing

Decision date (initial)

2023-04-18

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

programme hospitalier de recherche clinique en oncologie (PHRC-K de 2018)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Pharmacoeconomic, Others, Efficacy, Safety

To assess the efficacy of thromboprophylaxis in preventing venous thromboembolic events (VTE) in good and intermediate prognosis patients with metastatic germ cell cancer (GCT) undergoing first-line cisplatin-based chemotherapy with risk factors for developing a thromboembolic event (i.e. patients with elevated baseline LDH or BSA > 1.9 m² or RPLN> 5 cm).

Secondary objectives 4

1. To assess the safety of thromboprophylaxis in this population and evaluate the benefit risk ratio of the thromboprophylaxis.
2. To perform a cost-effectiveness analysis of thromboprophylaxis in preventing VTEs
3. To prospectively confirm the prognostic value for VTEs of the following risk factors in GCT: elevated LDH, BSA >1.9 m² and RPLN > 5 cm
4. To assess prospectively the prognostic value of other covariates as VTE risk factors: • Clinical covariates: central venous catheter (CVC) presence, smoking habits, physical inactivity, BMI • Laboratory covariates: platelets count, prothrombin time, partial thromboplastin time, albumin.

Conditions and MedDRA coding

Thromboprophylaxis in good and intermediate prognosis advanced germ cell tumors

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Diagnosis of good or intermediate prognosis of Germ Cell Tumor (according to the IGCCCG Group)
2. 2. ≥ 18 years
3. 3. Suitable for first-line cisplatin-based chemotherapy
4. 4. No prior systemic cytotoxic therapy
5. 5. Additional criteria for patients who will be randomized, (VTE high-risk patients):o LDH>1UNL and/or , o BSA > 1.9 m² and/or, o > 5 cm long axis retroperitoneal lymph nodes
6. 6. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
7. 7. Patients must be affiliated to a social security system or beneficiary of the same

Exclusion criteria 11

1. 1. Brain metastasis
2. 2. History of VTE
3. 3. Concomitant use of anticoagulants or antiaggregants
4. 4. Renal impairment defined as creatinine clearance less than 50 ml/min using Cockcroft-Gault formula
5. 5. Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWH) or to any of the excipients
6. 6. Any major surgery (i.e. open surgery lasting more than 45 minutes from opening to closure) within 4 weeks or planned during the study treatment period Severe uncontrolled high blood pressure (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)
7. 7. Low baseline platelet count (< 100 X 10 9 /L) or history of heparin-induced thrombocytopenia
8. 8. Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
9. 9. Extensive metastatic disease at high risk of bleeding, e.g. prevalent choriocarcinoma
10. 10. Participation in another clinical study with an investigational product during the last 4 weeks, and while on study treatment without the approval from sponsor
11. 11. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients undergoing a thromboembolic event (composite end point: venous or arterial thrombosis or embolism or unexplained death) occurring from randomization up to 6 weeks after D1 of the last cycle of chemotherapy or up to the residual masses surgery, whichever occurs first. Thromboembolic events will be reviewed by an independent clinical endpoint adjudication committee, blinded to the investigational treatment.

Secondary endpoints 13

1. Time to first occurrence a thromboembolic event (composite end point: venous or arterial thrombosis or embolism or unexplained death) from randomization up to 6 weeks after Day 1 of the last cycle of chemotherapy or until residual masses surgery.
2. Time to each component of the thromboembolic event composite endpoint from randomization up to 6 weeks after Day 1 of the last cycle of chemotherapy or until residual masses surgery.
3. Safety parameters include bleedings (major and clinically relevant non-major in agreement with the International Society on Thrombosis and Haemostasis recommendations, classified by the blinded adjudication committee), incidence of heparin-induced thrombopcytopenia, transfusions requirements and other serious or non-serious adverse events and deaths graded using the NCI-CTCAE v5.0 (Common Terminology Criteria for Adverse Events)
4. Comorbidity and need for hospitalization or extension of hospitalization length of stay (in patients already hospitalized for chemotherapy administration) for patients with TEE or adverse events related to thromboprophylaxis
5. Number of patients needed to treat to avoid a TEE.
6. Time to first occurrence of a thromboembolic event from inclusion up to 6 weeks after the last dose of chemotherapy or until residual masses surgery in GCT patients not presenting the already identified risk factors (...) and in high-risk GCT patients from the control group. Thromboembolic events will be reviewed by an independent clinical endpoint adjudication committee, in low and high-risk patients. The independent committee will be blinded to th
7. Evaluation of CVC (central venous catheter) presence, physical inactivity, smoking habits, germ cell histology, IGCCCGC prognostic group and baseline laboratory covariates as TEE risk factors (including platelets, prothrombin time, partial thromboplastin time, albumin)
8. Cost-effectiveness of thromboprophylaxis in high-risk patients
9. Proportion of patients undergoing symptomatic venous thrombosis,
10. Proportion of patients undergoing asymptomatic (incidental finding) venous thrombosis,
11. Proportion of patients undergoing pulmonary embolism
12. Proportion of patients with an unexplained death
13. The events taken into account for the computation of these proportions are those occurring from randomization up to 6 weeks after D1 of the last cycle of chemotherapy or up to the residual masses surgery,

Investigational products

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

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Institut Gustave Roussy

Contact name

Regulatory affairs officer

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Regulatory affairs officer

Locations

1 EU/EEA country · 26 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

Documents 11 files

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

Application history

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