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
Conditions
Interventions
Trade Name: Etoposide Accord 20mg/mL, solution à diluer pour perfusion
Product Name: Etoposide
Product Code: 3400955050001
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: CARBO
Sponsors
GUSTAVE ROUSSY
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 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 of child-bearing potential, 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. 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 Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 135 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Non-inclusion criteria common to the whole population 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 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 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 Human T-cell Leukemia Virus (HTLV) type 1 and 2 3. Patient with Hepatitis B surface antigen 4. Patient with Hepatitis C antibody 5. Patient with prior high-dose chemotherapy (HDCT) plus hematopoietic stem cell HSCs transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: Secondary objective 1: to prospectively collect tissue samples from patients with poor-prognosis NSGCT Secondary objective 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 Secondary objective 3: to assess whether an early systematic brain magnetic resonance imaging (MRI) can identify and allow treat better patients with asymptomatic oligo-brain metastases ;Primary end point(s): 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 (hCG and/or AFP) confirmed on two successive measures (except during the first two weeks of chemotherapy, because of the release phenomenon), or - a radiographic progression, based on conventional imaging (CT scan). In case of suspiscion of a growing teratoma syndrome (enlarging metastatic masses despite appropriate systemic chemotherapy and normalized serum markers), a pathological exam of the suspected lesions will be performed to confirm or infirm the diagnosis. A growing teratoma syndrome will be reported but not be considered as an event. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Response criteria Best tumor response will be assessed at the end of treatment (after chemotherapy or after surgery of residual masses, if any). - Patients with normal tumor markers and no clinical or radiologic evidence of disease will be classified as having achieved complete response to chemotherapy (cCR). - Patients with normal tumor markers and completely resected residual masses containing only necrosis or teratoma wil be classified as having achieved pathologic complete response (pCR). - Patients with normal tumor markers and completely resected masses containing viable cancer will be classified as having achieved surgical complete response (sCR). - Patients with incomplete resection of residual masses and normalized markers will be classified as partial response (PRm-). - Patients with incomplete resection of residual masses and non-normalized markers will be classified as partial response (PRm+). All other responses will be considered incomplete responses. Progressive disease (PD) is defined as an increase in tumor markers (hCG and/or AFP) confirmed on two successive measures (except during the first two weeks of chemotherapy, because of the release phenomenon), or a radiographic progression, based on conventional imaging (CT scan). Overall survival (OS) OS is defined as the time from the first day of the first cycle of BEP to the date of death due to any cause 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. We will use this prospective trial to validate that only a very limited number of these curable patients develop severe toxicity (specifically long-term neurotoxicity, secondary leukemia). Treatment-related mortality: Treatment-related mortality will be defined as any death | — |
Countries
France
Contacts
Public ContactAqsa YAR
GUSTAVE ROUSSY
Outcome results
None listed