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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Experimental | In arm patients receive a TI-CE regime based on paclitaxel and ifosfamide in cycles 1-2 and carboplatin and etoposide in cycles 3-5. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High-dose chemotherapy (TI- 2 cycles, CE- 3 cycles ) | Drug | 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 above 1*10^9/L. Patients will receive two cycles of TI followed by 3 cycles of CE in case at least 6*10^6 CD34+ stem cells will be harvested. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | Progression Free Survival 2-year | Up to 24 months post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | Overall survival (OS) 3-year | Up to 36 months post-treatment |
| Incidence of adverse events | All toxicities will be evaluated and recorded based on the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0). |
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Inclusion Criteria:
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 (ВЕРor EP).
4. Required Initial Laboratory Values:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna Semenova, MD, PhD | Contact | 8 (812) 439-95-05 | mirannia@yandex.ru |
| Name | Affiliation | Role |
|---|---|---|
| Aleksei M Belyaev, MD,DSc,Prof. | National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of Russia | Study Director |
| Tatyana Yu Semiglazova, MD,DSc,Prof. | National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of Russia |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of Russia | Recruiting | Saint Petersburg | Russian Federation | 197758 | Russia |
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| ID | Term |
|---|---|
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D013724 | Teratoma |
| D002822 | Choriocarcinoma |
| D018237 | Germinoma |
| D018239 | Seminoma |
| C537844 | Nonseminomatous germ cell tumor |
| D018240 | Endodermal Sinus Tumor |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D014328 | Trophoblastic Neoplasms |
| D000230 | Adenocarcinoma |
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| ID | Term |
|---|---|
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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|
| Up to 3 months post-therapy discontinuation |
| Validation of International Prognostic Factor Study Group stratification system | Evaluation of the efficacy of high-dose TI (2 cycles)-CE (3 cycles) chemotherapy in patients with germ cell tumors of gonadal and extragonadal localization who progressed after prior platinum-containing first-line chemotherapy and received high-dose TI (2 cycles)-CE (3 cycles) chemotherapy, depending on the prognosis group (IGCCCG classification (1997), IGCCCG Update Model (2021)). | Up to 3 years post-registration |
| Assessment of patients' quality of life | European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL. | also during the 5-year follow-up period. |
| Possibilities of rehabilitation | Evaluation of the impact of patient nutritional support and the relationship between patient nutrition and the incidence of non-hematologic complications (mucositis, colitis, infectious complications) | also during the 5-year follow-up period. |
| Assessment of the possibility of improving mobilization rates with the drug "Plerixafor" | In case of poor mobilization according to the criteria of the European Society of Bone Marrow Transplantation, the addition of Plerixafor at a dose of 24 mg to the mobilization is envisaged. An evaluation of the feasibility of improving mobilization rates with Plerixafor is planned. | 2 months |
| Response Rate | Incidence of complete, partial response, stable and progressive disease by RECIST 1.1 system | Every 8 weeks up to 6 months |
| Study Chair |
| D002277 |
| Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D011252 | Pregnancy Complications, Neoplastic |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D008649 | Mesonephroma |