Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors
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|ClinicalTrials.gov Identifier: NCT00047320|
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : February 27, 2014
Last Update Posted : February 14, 2018
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it is no longer present by conventional imaging and tumor markers from serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill more tumor cells.
PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without surgery and with or without high dose chemotherapy and peripheral stem cell transplantation, can increase response rates prior to radiation therapy and increase progression free and overall surviving patients with newly diagnosed intracranial germ cell tumors.
|Condition or disease||Intervention/treatment||Phase|
|Brain Tumor Central Nervous System Tumors Childhood Germ Cell Tumor||Drug: carboplatin Drug: etoposide Drug: ifosfamide Drug: thiotepa Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy||Phase 2|
- Determine the response rate of patients with non-germinomatous germ cell tumors treated with neoadjuvant chemotherapy.
- Determine the progression-free survival and overall survival of patients treated with neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy with or without autologous peripheral blood stem cell transplantation (PBSCT).
- Determine whether additional complete responses can be achieved after high-dose thiotepa and etoposide with PBSCT in patients with persistently positive markers, histological evidence of residual malignant elements, or unresectable residual tumors after initial neoadjuvant chemotherapy.
- Determine patterns of recurrence in patients treated with this regimen.
- Correlate tumor marker response with radiographic and clinical measures of response, as well as findings at second-look surgery in patients with radiological evidence of residual disease.
- Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts recover. Courses are 3 weeks in duration.
- Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in duration.
Patients undergo re-evaluation. Patients with a complete response (CR) go directly to radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients with less than a CR are encouraged to undergo second-look surgery.
After second-look surgery, patients with a CR or a partial response (PR) go directly to radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with peripheral blood stem cell rescue (PBSC) followed by radiotherapy.
- Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0. Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC daily.
- Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks beginning after recovery from induction chemotherapy or second-look surgery or within 9 weeks after PBSC reinfusion.
Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||104 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study To Assess The Ability Of Neoadjuvant Chemotherapy Plus/Minus Second Look Surgery To Eliminate All Measurable Disease Prior To Radiotherapy For NGGCT|
|Study Start Date :||January 2004|
|Actual Primary Completion Date :||February 2009|
|Actual Study Completion Date :||February 2009|
Experimental: Radiation Therapy (CR from Induction)
Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Other Name: Craniospinal irradiation (CSI) followed by boost radiation to the sites of gross disease at diagnosis.
- Response to Induction Chemotherapy [ Time Frame: 18 weeks ]A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.
- The Probability of Event-free Survival (EFS) [ Time Frame: At 3 years from study entry ]Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate.
- Progression-free Survival (PFS) [ Time Frame: At 3 years from study entry ]Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate.
- Overall Survival (OS) [ Time Frame: At 3 years from study entry ]Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate.
- Number of Patients Experiencing Toxic Death [ Time Frame: During chemotherapy (up to 18 weeks) ]Toxic death, defined as death predominantly attributable to treatment-related causes.
- Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity [ Time Frame: During chemotherapy(up to 18 weeks) ]The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00047320
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|Study Chair:||Stewart Goldman, MD||Ann & Robert H Lurie Children's Hospital of Chicago|