A prospective program aiming at improving outcome for young adults with poor-prognosis non seminomatous germ-cell tumors (VAPOR (GETUG T06))

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

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

Trial duration

11 Apr 2023 → ongoing

Decision date (initial)

2023-08-04

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRC 2015

External identifiers

EU CT number

2023-505040-19-00

EudraCT number

2021-006638-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of this prospective research program that aims at improving outcome for young adults with poor-prognosis NSGCT is to validate prospectively the efficacy and safety of a personalized treatment based on early tumor marker kinetic assessment in real life for patients with poor-prognosis NSGCT.

Secondary objectives 3

1. to prospectively collect tissue samples from patients with poor-prognosis NSGCT
2. to assess the efficacy and safety of early surgery and/or high-dose chemotherapy with transplant in patients with a mediastinal NSGCT and an unfavorable decline
3. to assess whether an early systematic brain magnetic resonance imaging (MRI) can identify and allow treat better patients with asymptomatic oligo-brain metastases

Conditions and MedDRA coding

Non-seminomatous germ-cell tumors (including testis, retroperitoneal and mediastinal primaries) with a disseminated disease (clinical stages II or III according to AJCC 8th edition) and classified as poor prognosis according to IGCCCG criteria.

Regulatory references

Scientific advice from competent authorities

Comite De Protection Des Personnes Ile De France XI, National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male patient older than 16 years old on day of signing informed consent
2. Patient with evidence of NSGCT based on histologic examination or based on clinical evidence and elevated serum hCG or AFP levels (in case of clinical emergency, therapy can be started before pathologic sample is obtained if tumor markers are highly elevated)
3. Patient with testicular, retroperitoneal, or mediastinal primary site
4. Patient with evidence of disseminated disease (clinical stages II or III according to AJCC 8th edition)
5. Patient with disease classified as poor prognosis according to IGCCCG criteria: - Primary mediastinal NSGCT or, - Non-pulmonary visceral metastases or, - hCG > 50 000 UI/L, or AFP > 10 000 ng/mL, or LDH > 10 times the upper normal value
6. Patient with adequate renal function: measured or calculated (by Cockcroft formula) creatinine clearance > 60 mL/min. Cockcroft formula: CrCl = [(140-age) x weight in kg]/[72 x serum creatinine (mg/dL)]
7. Patient with absolute granulocyte count  1,500/mm3, platelets  100 000 mm3, bilirubine  1.5x the upper limit of normal value.
8. Patient with a contra-indication of undergoing any brain MRI are eligible, but will not be part of the diagnostic study part
9. Patient (and his legal guardian for under-18 patient) who had understood, signed and dated the informed consent form
10. Patient affiliated to social security system or beneficiary of the same
11. Male must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 6 months after the last treatment intake.
12. Inclusion criteria specific to the phase 2 study in patients with unfavorable serum marker decrease and mediastinal primary tumor (to be confirmed before the end of the 1st BEP cycle) 1. Patient (and his legal guardian for under-18 patient) who had understood, signed and dated the specific Phase II informed consent form 2. Patient with mediastinal primary site 3. Patient with unfavorable serum marker decrease evaluated at D18-D21 of the first BEP-chemotherapy

Exclusion criteria 6

1. Patient infected by the Human Immunodeficiency Virus (HIV)
2. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
3. Patient with prior chemotherapy. Patients who have received a first cycle of cisplatin-base chemotherapy (BEP) for their poor-prognosis NSGCT are eligible as far as tumor marker decline can be assessed at day 18-21.
4. Patient with previous malignancy, except for basal-cell carcinoma of the skin
5. Known allergy or hypersensitivity to any of the study drugs
6. Non inclusion criteria specific to the phase 2 study in patients with unfavorable serum marker decrease and mediastinal primary tumor (to be confirmed before the end of the 1st BEP cycle) 1. Patient (and his legal guardian for under-18 patient) who withdraws his consent 2. Patient with Hepatitis B surface antigen 3. Patient with Hepatitis C antibody 4. Patient with prior high-dose chemotherapy (HDCT) plus hematopoietic stem cell HSCs transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary evaluation criterion of the study is progression-free survival (PFS). PFS will be determined from the first day of the first cycle of BEP to the date of progression or death due to any cause, whichever occurs first. Progression will be defined as: - an increase in tumor markers (...), or - a radiographic progression (...)

Secondary endpoints 4

1. Efficacy: - Response criteria Best tumor response will be assessed at the end of treatment (after chemotherapy or after surgery of residual masses, if any) (...); - Overall survival (OS) (...)
2. Tolerance: Toxicity: All toxicities will be evaluated and recorded based on the NCI common toxicity criteria (CTCAE v5.0). They will be described by frequency and grade, by cycle and over all cycles, with the maximum grade over all cycles used as the summary measure for each patient. (...) Treatment-related mortality: (...)
3. Quality of life – Patient-related outcomes: The following questionnaires will be used: QLQ-C30, QLQ-TC26, FACT-GOG-NTX and IPQ
4. Specific endpoints for the diagnostic study assessing the addition of an early systematic brain MRI: - The proportion of initially brain metastases-free patients who are diagnosed with brain metastases early on a systematic brain MRI performed at the middle of the therapeutic strategy. This proportion will be calculated with its exact 95% confidence interval (...) - The survival after brain metastases relapse

Investigational products

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

Test 1

Comparator 9

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

Cleo NUSSBAUM

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Cleo NUSSBAUM

Locations

1 EU/EEA country · 24 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 30 files

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

Application history

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