Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors
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| ClinicalTrials.gov Identifier: NCT01602666 |
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Recruitment Status :
Active, not recruiting
First Posted : May 21, 2012
Results First Posted : December 16, 2020
Last Update Posted : January 26, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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Brief Summary:
This phase II trial studies how well chemotherapy followed by radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors that have not spread to other parts of the brain, spinal canal, or body (localized). Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy followed by radiation therapy may kill more tumor cells.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Central Nervous System Nongerminomatous Germ Cell Tumor Childhood Central Nervous System Germinoma | Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Carboplatin Drug: Etoposide Drug: Ifosfamide Radiation: Intensity-Modulated Radiation Therapy | Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 262 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT) |
| Actual Study Start Date : | May 29, 2012 |
| Actual Primary Completion Date : | September 30, 2019 |
| Estimated Study Completion Date : | December 31, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (combination chemotherapy, radiation therapy)
See Detailed Description
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Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3D-CRT
Other Names:
Drug: Carboplatin Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Radiation: Intensity-Modulated Radiation Therapy Undergo IMRT
Other Names:
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Primary Outcome Measures :
- 3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation [ Time Frame: 3 years ]Binomial estimate of the 3-year PFS rate defined as "Yes" for patients who were followed up per protocol and were progression free at 3-years, and "No" for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from enrollment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
- 3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy [ Time Frame: 3 years ]Binomial estimate of the 3-year PFS rate defined as "Yes" for patients who were followed up per protocol and were progression free at 3-years, and "No" for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from initiation of treatment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
- Neurocognitive Function Using the ALTE07C1 Protocol [ Time Frame: Up to 5 years ]
Estimated scores for processing speed, attention/concentration, and estimated IQ at 9 months, 30 months and 60 months, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma).
Estimated change over these three timepoints for processing speed, attention/concentration, and estimated IQ, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma).
Secondary Outcome Measures :
- Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR) [ Time Frame: Up to 3 years ]Kaplan Meier estimate of the 3-year PFS is provided. PFS is the time interval measured from enrollment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
- Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed [ Time Frame: Up to 3 years ]Kaplan Meier estimate of the 3-year overall survival (OS) is provided. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis.
- Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL [ Time Frame: Up to 3 years ]Kaplan Meier estimate of the 3-year PFS rate is provided. PFS is the time interval measured from initiation of treatment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
- Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL [ Time Frame: Up to 3 years ]Kaplan Meier estimate of the 3-year overall survival (OS) is provided for each group. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis.
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| Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Patients must be newly diagnosed with localized primary CNS NGGCT (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ cell tumors located in the suprasellar, pineal, bifocal (pineal + suprasellar) and ventricles are eligible; tumors present in the above mentioned locations and with unifocal parenchymal extension are eligible
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Stratum 1(NGGCT): Patients must have one of the following criteria:
- Patients with serum and/or CSF hCGbeta > 100 mIU/mL or any elevation of serum and/or CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the institutional normal are eligible, irrespective of biopsy results
- Patients with any of the following elements on biopsy/resection are eligible, irrespective of serum and/or CSF hCGbeta and AFP levels: endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma, and mixed GCT with malignant GCT elements
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Stratum 2 (Germinoma): Patients must have both serum and CSF markers obtained (unless obtaining CSF is medically contraindicated) and must have one of the following criteria to be eligible:
- Patients with institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) AND hCGbeta 5 to =< 50 mIU/mL in serum and/or CSF (unless medically contraindicated) (only 1 is required to be elevated) are eligible; no histologic confirmation required
- Patients with bifocal (pineal + suprasellar) involvement or pineal lesion with diabetes insipidus (D1) AND hCGbeta =< 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible; no histologic confirmation required
- Patients with histologically confirmed germinoma or germinoma mixed with mature teratoma and hCGbeta =< 100 mIU/mL in serum and/or CSF and institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible
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- All patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment; if surgical resection is performed, patients must have pre-operative and post-operative cranial MRI with and without gadolinium; the post-operative brain MRI should be obtained within 72 hours of surgery; if patient has a biopsy only, post-operative cranial MRI is recommended but not required; all patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment; Note: if the spine study is performed for the first time after surgical resection or biopsy, it is recommended to be obtained with and without gadolinium
- Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated; if a patient undergoes surgery and lumbar CSF cannot be obtained at this time, then it should be performed at least 10 days following surgery before study enrollment; false positive cytology can occur within 10 days of surgery; Note: patients with positive CSF cytology obtained prior to 10 days after surgery may have cytology repeated to determine eligibility
- Patients must have CSF tumor markers obtained prior to enrollment unless medically contraindicated; ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred; in case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first
- Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123; patients must be enrolled within 31 days of definitive diagnostic surgery (day 0) or clinical diagnosis
- Peripheral absolute neutrophil count (ANC) >= 1,000/uL
- Platelet count >= 100,000/uL (transfusion independent)
- Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
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Creatinine clearance or radioisotope glomular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows:
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) and 1.4 mg/dL (female) (>= 16 years of age)
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times ULN
- Patients with seizure disorder may be enrolled if well controlled
- Patients must not be in status, coma, or assisted ventilation prior to study enrollment
Exclusion Criteria:
- Patients with mature teratoma or completely resected immature teratoma with normal tumor markers are not eligible
- Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible
- Patients with metastatic disease by cranial or spinal MRI evaluation or CSF cytology (unless medically contraindicated) are not eligible
- Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids
- Female patients who are pregnant are ineligible
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Information from the National Library of Medicine
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): NCT01602666
Locations
Show 167 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Ute K Bartels | Children's Oncology Group |
Study Documents (Full-Text)
Documents provided by Children's Oncology Group:
Documents provided by Children's Oncology Group:
Study Protocol and Statistical Analysis Plan [PDF] June 1, 2015
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT01602666 |
| Other Study ID Numbers: |
ACNS1123 NCI-2012-01967 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ACNS1123 CDR0000734032 S12-02807 ACNS1123 ( Other Identifier: Children's Oncology Group ) ACNS1123 ( Other Identifier: CTEP ) K12CA086913 ( U.S. NIH Grant/Contract ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | May 21, 2012 Key Record Dates |
| Results First Posted: | December 16, 2020 |
| Last Update Posted: | January 26, 2023 |
| Last Verified: | December 2022 |
Additional relevant MeSH terms:
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Neoplasms, Germ Cell and Embryonal Germinoma Neoplasms by Histologic Type Neoplasms Carboplatin Etoposide Etoposide phosphate Ifosfamide Isophosphamide mustard Podophyllotoxin Antineoplastic Agents Antineoplastic Agents, Phytogenic |
Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents Keratolytic Agents Dermatologic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators |