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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00047320
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : February 27, 2014
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE October 3, 2002
First Posted Date  ICMJE January 27, 2003
Results First Submitted Date  ICMJE January 15, 2014
Results First Posted Date  ICMJE February 27, 2014
Last Update Posted Date February 14, 2018
Study Start Date  ICMJE January 2004
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description

OBJECTIVES:

  • 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.

OUTLINE:

  • Induction chemotherapy:

    • 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain Tumor
  • Central Nervous System Tumors
  • Childhood Germ Cell Tumor
Intervention  ICMJE
  • Drug: carboplatin
    Given IV
    Other Names:
    • Paraplatin
    • NSC #241240
  • Drug: etoposide
    Given IV
    Other Names:
    • VP-16
    • VePesid
    • Etopophos
    • NSC #141540
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Isophosphamide
    • Iphosphamide
    • Z4942
    • Ifex
    • NSC #109724
  • Drug: thiotepa
    Given IV
    Other Names:
    • Tespa
    • Thiophosphamide
    • Triethylenethiophosphoramide Tspa
    • WR-45312
    • NSC #6396
  • Procedure: adjuvant therapy
  • Procedure: conventional surgery
  • Procedure: neoadjuvant therapy
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: radiation therapy
    craniospinal irradiation
    Other Name: Craniospinal irradiation (CSI) followed by boost radiation to the sites of gross disease at diagnosis.
Study Arms  ICMJE 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.
Interventions:
  • 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
Publications * Fangusaro J, Wu S, MacDonald S, Murphy E, Shaw D, Bartels U, Khatua S, Souweidane M, Lu HM, Morris D, Panigrahy A, Onar-Thomas A, Fouladi M, Gajjar A, Dhall G. Phase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study. J Clin Oncol. 2019 Dec 1;37(34):3283-3290. doi: 10.1200/JCO.19.00701. Epub 2019 Sep 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 22, 2013)
104
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 2009
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • One of the following diagnoses:

    • Histologically confirmed intracranial non-germinomatous germ cell tumor (NGGCT) of 1 of the following types:

      • Endodermal sinus tumor (yolk sac tumor)
      • Embryonal carcinoma
      • Choriocarcinoma
      • Immature teratoma and teratoma with malignant transformation
      • Mixed germ cell tumor
    • Histologically confirmed germinoma with elevation of serum/CSF beta human chorionic gonadotropin (HCG) levels greater than 50 mIU/mL or any serum/CSF alpha-fetoprotein (AFP) levels greater than 10 ng/ml or above institutional norm
    • Histologically unconfirmed pineal and/or suprasellar tumors with serum/CSF beta HCG levels greater than 50 mIU/mL or AFP levels greater than 10 ng/ml or above institutional norm
  • Patients with normal AFP and beta HCG < 50 mIU/mL without histologic diagnosis of a NGGCT or patients with pure germinoma without elevation of tumor marker are ineligible
  • Initial diagnosis within the past 31 days

PATIENT CHARACTERISTICS:

Age

  • 3 to 24 at diagnosis

Performance status

  • No minimum performance level

Life expectancy

  • At least 8 weeks

Hematopoietic

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3 (transfusion independent)
  • Hemoglobin at least 10.0 g/dL (transfusion allowed)

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • ALT no greater than 2.5 times ULN

Renal

  • Creatinine no greater than 1.5 times ULN OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Pulmonary

  • No assisted ventilation

Other

  • Seizure disorders allowed
  • No patients in status or coma
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patient must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Prior corticosteroids allowed
  • Concurrent corticosteroids allowed
  • Concurrent endocrine replacement therapy allowed (e.g., L-thyroxine, testosterone, estrogen, desmopressin acetate)
  • No concurrent growth hormone therapy

Radiotherapy

  • Not specified

Surgery

  • More than 1 prior surgery allowed

Other

  • No other prior therapy for malignancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 24 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   New Zealand,   Switzerland,   United States
Removed Location Countries Netherlands,   Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT00047320
Other Study ID Numbers  ICMJE ACNS0122
CDR0000257664 ( Other Identifier: Clinical Trials.gov )
COG-ACNS0122 ( Other Identifier: Children's Oncology Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Children's Oncology Group
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Children's Oncology Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Stewart Goldman, MD Ann & Robert H Lurie Children's Hospital of Chicago
PRS Account Children's Oncology Group
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP