CNS Germ Cell Tumor
Conditions
Brief summary
This study will look to see how well patients with relapsed or recurrent intracranial germ cell tumors respond to the new combination of chemotherapy (in induction)of Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) followed by consolidation chemotherapy and autologous stem cell rescue.
Interventions
DRUGGemcitabine, Paclitaxel and Oxaliplatin (GemPOx).
Two to four cycles of induction therapy with GemPOx followed by consolidation and ASCT.
Sponsors
Nationwide Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* ICGCT including pure germinoma and MMGCT. * Patients with histologically proven germinoma and MMGCT, including endodermal sinus tumor (yolk sac tumor), embryonal carcinoma, choriocarcinoma and mixed germ cell tumor will be eligible for the study. * Patients with mature/immature teratoma who have tumor marker elevations are eligible on this study. * Patient with ONLY mature and/or immature teratoma are ineligible in the absence of the tumor marker elevations.
Exclusion criteria
* Patients with ICGCTs who are newly diagnosed are excluded from the study. * Patients with the diagnosis of mature or immature teratoma in the absence of tumor marker elevations are excluded from the study. * Patients who are pregnant or breastfeeding are excluded from the study. * Patients who have received previously a high dose chemotherapy regimen and autologous transplant are excluded from this study. * Patients who have received gemcitabine, oxaliplatin and/or paclitaxel are excluded from this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 16-32 weeks depending on individual patient response (remaining disease burden) to chemotherapy | To estimate response rate after at least two and up to four courses of induction chemotherapy with GemPOx regimen in patients with recurrent intracranial MMGCT |
| The Rate of Completion of Induction Chemotherapy and Progression to High-dose Chemotherapy (HDC) With Autologous Hematopoietic Progenitor Cell Rescue (AuHPCR) | Mean follow-up of 44 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS and PFS | 2 years, 3 years and 5 years | To assess the overall survival (OS) and event-free survival (EFS) of patients treated on the GemPOx induction regimen followed by the HDC and AuHPCR in patients with progressive or recurrent CNS GCT. We hypothesize that specific CSF miRNA will prove to be accurate markers for tumor presence and predictors of response to therapy, with normalization being associated with improved progression-free survival (PFS) in patients under treatment for recurrent central nervous system (CNS) germ cell tumors (GCT). |
Countries
United States
Participant flow
Pre-assignment details
Nine patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least two cycles of GemPOx, of which all but one had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) Two to four cycles of induction therapy with open label GemPOx followed by consolidation and autologous stem cell transplant (ASCT).
Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx).: Two to four cycles of induction therapy with GemPOx followed by consolidation and ASCT.
Nine patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least two cycles of GemPOx, of which all but one had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | — |
|---|---|---|
| Age, Categorical <=18 years | 5 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 5 Participants | — |
| Patients enrolled on study with eligible diagnosis of CNS GCT including pure germinoma and MMGCT | 9 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 10 participants | — |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 9 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
Response Rate
To estimate response rate after at least two and up to four courses of induction chemotherapy with GemPOx regimen in patients with recurrent intracranial MMGCT
Time frame: 16-32 weeks depending on individual patient response (remaining disease burden) to chemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Response Rate | CR, Complete Response | 0 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Response Rate | PR, Partial Response | 0 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Response Rate | SD, Stable Disease | 4 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Response Rate | PD, Progressive Disease | 2 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Response Rate | PR1, Partial Response with Normal Markers | 3 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Response Rate | PR2, Partial Response with Abnormal (but not rising) Markers | 0 Participants |
Primary
The Rate of Completion of Induction Chemotherapy and Progression to High-dose Chemotherapy (HDC) With Autologous Hematopoietic Progenitor Cell Rescue (AuHPCR)
Time frame: Mean follow-up of 44 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | The Rate of Completion of Induction Chemotherapy and Progression to High-dose Chemotherapy (HDC) With Autologous Hematopoietic Progenitor Cell Rescue (AuHPCR) | 7 Participants |
Secondary
OS and PFS
To assess the overall survival (OS) and event-free survival (EFS) of patients treated on the GemPOx induction regimen followed by the HDC and AuHPCR in patients with progressive or recurrent CNS GCT. We hypothesize that specific CSF miRNA will prove to be accurate markers for tumor presence and predictors of response to therapy, with normalization being associated with improved progression-free survival (PFS) in patients under treatment for recurrent central nervous system (CNS) germ cell tumors (GCT).
Time frame: 2 years, 3 years and 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | OS and PFS | 2-year PFS | 66.7 Percentage of patients |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | OS and PFS | 3-year PFS | 55.6 Percentage of patients |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | OS and PFS | 5-year PFS | 44.4 Percentage of patients |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | OS and PFS | 2-year OS | 66.7 Percentage of patients |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | OS and PFS | 3-year OS | 66.7 Percentage of patients |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | OS and PFS | 5-year OS | 55.6 Percentage of patients |
Post Hoc
Last Patient Follow-up Outcome
The outcome of each patient at the last point of follow-up
Time frame: Months in follow-up (up to 86 months follow-up)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Last Patient Follow-up Outcome | PR, Partial Response | 0 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Last Patient Follow-up Outcome | SD, Stable Disease | 0 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Last Patient Follow-up Outcome | PD, Progressive Disease | 0 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Last Patient Follow-up Outcome | NED, No Evidence of Disease | 4 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Last Patient Follow-up Outcome | DOD, Dead of Disease | 4 Participants |
| Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) | Last Patient Follow-up Outcome | Unknown, Lost to Follow-up | 1 Participants |