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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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00047320
First received: October 3, 2002
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Response to Induction Chemotherapy [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size without complete disappearance of tumor after induction chemotherapy will be considered to have experienced response.


Secondary Outcome Measures:
  • Event-free Survival [ Time Frame: From time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. ] [ Designated as safety issue: No ]
  • Progression-free Survival [ Time Frame: From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse or progressive disease ] [ Designated as safety issue: No ]
    From study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms, are censored in this analysis.

  • Overall Survival [ Time Frame: Time from study entry to death from any cause ] [ Designated as safety issue: No ]
  • Toxic Death [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
    Defined as death predominantly attributable to treatment-related causes.

  • Occurrence of Nonhematological Grade 4 Toxicity [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 104
Study Start Date: January 2004
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   3 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047320

  Show 106 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Stewart Goldman, MD Ann & Robert H Lurie Children's Hospital of Chicago
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00047320     History of Changes
Other Study ID Numbers: ACNS0122, CDR0000257664, COG-ACNS0122
Study First Received: October 3, 2002
Results First Received: January 15, 2014
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
childhood central nervous system germ cell tumor
childhood teratoma
recurrent childhood malignant germ cell tumor
childhood central nervous system choriocarcinoma
childhood central nervous system embryonal tumor
childhood central nervous system germinoma
childhood central nervous system mixed germ cell tumor
childhood central nervous system teratoma
childhood central nervous system yolk sac tumor
recurrent childhood central nervous system embryonal tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Neoplasms
Neoplasms, Germ Cell and Embryonal
Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Nervous System Diseases
Carboplatin
Etoposide
Ifosfamide
Isophosphamide mustard
Thiotepa
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014