## Protocol Section
### Identification Module
**NCT ID:** NCT06418789

**Acronym:** GERMAN

**Brief Title:** High-dose Chemotherapy as Second-line Drug Therapy for Relapsed Germ Cell Tumors

**Official Title:** High-dose Chemotherapy as Second-line Drug Therapy for Relapsed Germ Cell Tumors

#### Organization Study ID Info
**ID:** German2
#### Organization
**Class:** OTHER
**Full Name:** N.N. Petrov National Medical Research Center of Oncology
### Status Module
#### Completion Date
**Date:** 2029-03-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-13

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2029-03-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-08
**Study First Submit QC Date:** 2024-05-13
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** N.N. Petrov National Medical Research Center of Oncology

#### Responsible Party

**Investigator Affiliation:** N.N. Petrov National Medical Research Center of Oncology

**Investigator Full Name:** Anna Igorevna Semenova

**Investigator Title:** clinical oncologist

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

**Detailed Description:** 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.

### Conditions Module

**Conditions:**

- Germ Cell Tumor

**Keywords:**

- Germ Cell Tumor

- Teratoma

- Choriocarcinoma

- Germinoma

- Childhood Teratoma

- Extragonadal Seminoma

- Seminoma

- Non-seminomatous Germ Cell Tumor

- Yolk Sac Tumor

- Mixed Germ Cell Tumor

- Malignant Germ Cell Neoplasm

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 25

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Drug: High-dose chemotherapy (TI- 2 cycles, CE- 3 cycles )

**Label:** Group 1

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Group 1

**Description:** 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.

**Name:** High-dose chemotherapy (TI- 2 cycles, CE- 3 cycles )

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Progression Free Survival 2-year

**Measure:** Progression Free Survival (PFS)

**Time Frame:** Up to 24 months post-treatment

#### Secondary Outcomes

**Description:** Overall survival (OS) 3-year

**Measure:** Overall survival (OS)

**Time Frame:** Up to 36 months post-treatment

**Description:** All toxicities will be evaluated and recorded based on the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0).

**Measure:** Incidence of adverse events

**Time Frame:** Up to 3 months post-therapy discontinuation

**Description:** 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)).

**Measure:** Validation of International Prognostic Factor Study Group stratification system

**Time Frame:** Up to 3 years post-registration

**Description:** 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.

**Measure:** Assessment of patients' quality of life

**Time Frame:** also during the 5-year follow-up period.

**Description:** 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)

**Measure:** Possibilities of rehabilitation

**Time Frame:** also during the 5-year follow-up period.

**Description:** 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.

**Measure:** Assessment of the possibility of improving mobilization rates with the drug "Plerixafor"

**Time Frame:** 2 months

**Description:** Incidence of complete, partial response, stable and progressive disease by RECIST 1.1 system

**Measure:** Response Rate

**Time Frame:** Every 8 weeks up to 6 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Patient is able to provide informed consent and sign approved consent forms to participate in the study.
2. Males ≥ 18 years of age at the time of signing the IC Form.
3. 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).

Exclusion Criteria:

1. Primary CS of the brain
2. Administration of ≥2 lines of prior drug therapy for disseminated GO.
3. 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.
4. Conditions that limit the patient's ability to fulfill the requirements of the protocol (psychiatric disorders, drug or alcohol dependence).

**Minimum Age:** 18 Years

**Sex:** MALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** mirannia@yandex.ru

**Name:** Anna Semenova, MD, PhD

**Phone:** 8 (812) 439-95-05

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Saint Petersburg

**Contacts:**

***Contact 1:***

- **Name:** Anna I Semenova, MD, PhD

- **Role:** CONTACT

**Country:** Russian Federation

**Facility:** National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of Russia

**Status:** RECRUITING

**Zip:** 197758

#### Overall Officials

**Official 1:**

**Affiliation:** National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of Russia

**Name:** Aleksei M Belyaev, MD,DSc,Prof.

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** National Medical Research Center of Oncology named after N.N.Petrov Ministry of health of Russia

**Name:** Tatyana Yu Semiglazova, MD,DSc,Prof.

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009369

- Term: Neoplasms

- ID: D000009370

- Term: Neoplasms by Histologic Type

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M20386

- Name: Endodermal Sinus Tumor

- Relevance: LOW

- As Found: Unknown

- ID: M16494

- Name: Teratoma

- Relevance: LOW

- As Found: Unknown

- ID: M20383

- Name: Germinoma

- Relevance: LOW

- As Found: Unknown

- ID: M20385

- Name: Seminoma

- Relevance: LOW

- As Found: Unknown

- ID: M6062

- Name: Choriocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: HIGH

- As Found: Germ cell tumor

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: T2475

- Name: Germ Cells Tumors

- Relevance: HIGH

- As Found: Germ cell tumor

- ID: T1031

- Name: Central Nervous System Germinoma

- Relevance: LOW

- As Found: Unknown

- ID: T5604

- Name: Testicular Seminoma

- Relevance: LOW

- As Found: Unknown

- ID: T4160

- Name: Nonseminomatous Germ Cell Tumor

- Relevance: LOW

- As Found: Unknown

- ID: T3579

- Name: Malignant Germ Cell Tumor

- Relevance: LOW

- As Found: Unknown

- ID: T1179

- Name: Choriocarcinoma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M19537

- Name: Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M18650

- Name: Carboplatin

- Relevance: LOW

- As Found: Unknown

- ID: M8191

- Name: Etoposide

- Relevance: LOW

- As Found: Unknown

- ID: M231

- Name: Albumin-Bound Paclitaxel

- Relevance: LOW

- As Found: Unknown

- ID: M10117

- Name: Ifosfamide

- Relevance: LOW

- As Found: Unknown

- ID: M341643

- Name: Etoposide phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M230811

- Name: Isophosphamide mustard

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
