High-dose Chemotherapy as Second-line Drug Therapy for Relapsed Germ Cell Tumors

Обзор

This is a prospective, single-center, non-randomized phase II study. Patients with germ cell tumors of gonadal and extragonadal localization who have progressed after prior platinum-containing first-line chemotherapy will receive high-dose chemotherapy with TI (2 cycles) folollowed by high dose CE chemotherapy with autologous stem cell transplantation (3 cycles). The primary endpoint of the study is to evaluate the efficacy high-dose chemotherapy as second-line drug therapy for patients with advanced germ cell tumors.

Подробное описание

Germ cell tumors are curable diseases. Only a small proportion of patients fail to be cured: those who experience a primary resistance to chemotherapy and those who relapsed after first line conventional dose cisplatin-based chemotherapy. Nowadays, there is heterogeneity of practice in salvage approaches. This includes conventional chemotherapy high dose chemotherapy with autologous stem cell transplant. Best choice of the therapy strategy is an unmet clinical need now. This is why this single-center, non-randomized phase II study will be conducted at the N.N. Petrov National Medical Research Center of Oncology. Patients with germ cell tumors of gonadal and extragonadal localization who have progressed after prior platinum-containing first-line chemotherapy will receive two cycles of high-dose TI (Paclitaxel 200mg/m² on day 1, Ifosfamide 2000mg/m² daily from days 1 to 3 of 14-day cycle. G-CSF 10 micrograms/Kg SC daily day on days 6-14 day or until CD34 harvest; leukapheresis will be performed starting on day 11 in case of CD45+CD34+ blood level above 20x10\^6/L is achieved), followed by three cycles of high dose CE (Carboplatin AUC=8 IV daily days -4 to -2, Etoposide 400mg/m\^2 IV daily days -4 to -2, autlologous stem cell transplantation at day 0, GCSF support from day 4.) The primary endpoint of the study is to evaluate the efficacy by measuring progression-free survival. The secondary endpoints of the trial are overall survival, response rate by RECIST, safety and prognostic factors analysis.

Вмешательства

• Препарат High-dose chemotherapy (TI- 2 cycles, CE- 3 cycles )
  TI: Paclitaxel 200mg/m² on day 1, Ifosfamide 2000mg/m² daily from days 1 to 3 of 14-day cycle. G-CSF 10 micrograms/Kg SC daily day on days 6-14 day or until CD34 harvest. Leukapheresis will be performed starting on day 11 in case blood level of CD45+CD34+ above 20x10\^6/L is achieved. CE: Carboplatin AUC=8 IV daily days -4 to -2, Etoposide 400mg/m\^2 IV daily days -4 to -2, autlologous stemm cell transplantation \>=2\*10\^6/Kg at day 0, GCSF support from day 4 until the recovery of neutrophils

Первичные конечные точки

• Progression Free Survival (PFS) [Срок оценки: Up to 24 months post-treatment]

Вторичные конечные точки (7)

• Overall survival (OS) [Срок оценки: Up to 36 months post-treatment]
• Incidence of adverse events [Срок оценки: Up to 3 months post-therapy discontinuation]
• Validation of International Prognostic Factor Study Group stratification system [Срок оценки: Up to 3 years post-registration]
• Assessment of patients' quality of life [Срок оценки: also during the 5-year follow-up period.]
• Possibilities of rehabilitation [Срок оценки: also during the 5-year follow-up period.]
• Assessment of the possibility of improving mobilization rates with the drug "Plerixafor" [Срок оценки: 2 months]
• Response Rate [Срок оценки: Every 8 weeks up to 6 months]

Критерии участия

Критерии включения

• Patient is able to provide informed consent and sign approved consent forms to participate in the study.
• Males ≥ 18 years of age at the time of signing the IC Form.
• Histologically verified diagnosis of GO (seminomatous, non-seminomatous).

2\. Any (gonadal and extragonadal (retroperitoneal, mediastinal, etc.)) localization of primary GO.

3\. Progression after 3 or 4 cycles of platinum-containing first-line chemotherapy (ВЕР or EP).

4\. Required Initial Laboratory Values:

• Hemoglobin ≥ 90 g/L;
• neutrophils ≥ 1.5 x 109/L;
• platelets ≥ 75 x 109/L;
• creatinine ≥ 1.5 x HGH (or CKF ≤ 60 mL/min);
• ALT or AST ≥ 2.5 x HGN (5 x HGN for patients with liver metastases);
• bilirubin ≥ 1.5 x IUH (except for patients with Gilbert syndrome, in whom total bilirubin levels should not exceed 50 μmol/L);
• alkaline phosphatase ≥ 2.5 x IUH. 5. Absence of neurologic symptoms in the presence of CNS metastases (asymptomatic CNS metastases are acceptable).

Критерии исключения

• Primary CS of the brain
• Administration of ≥2 lines of prior drug therapy for disseminated GO.
• Presence of active hepatitis B or hepatitis C, HIV infection, acute infectious disease, or activation of chronic infectious disease less than 28 days prior to study inclusion.
• Conditions that limit the patient's ability to fulfill the requirements of the protocol (psychiatric disorders, drug or alcohol dependence).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of — Saint Petersburg

Идентификаторы

NCT: NCT06418789 · German2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗