A Phase II Trial Evaluating Chemotherapy Followed by Response-Based Reduced Radiation Therapy for Patients With Central Nervous System Germinomas

Status: Recruiting
Location: See all (93) locations...
Intervention Type: Procedure, Drug, Radiation, Other
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin \& Etoposide) works in treating children with central nervous system (CNS) germinomas. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Researchers want to see if lowering the dose of standard radiotherapy (RT) after chemotherapy can help get rid of CNS germinomas with fewer long-term side effects.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 3
Maximum Age: 29
Healthy Volunteers: f
View:

• Patients must be ≥ 3 years and \< 30 years at the time of study enrollment

• Patients must be newly-diagnosed primary localized germinoma of the suprasellar and/or pineal region by pathology and/or serum and/or CSF hCGbeta 5-50 mIU/mL AND institutional normal AFP (or ≤ 10 ng/mL if no institutional normal exists), including tumors with contiguous ventricular or unifocal parenchymal extension. No histologic confirmation required

• Patients with EITHER (A) bifocal (pineal + suprasellar) involvement OR (B) pineal lesion with diabetes insipidus (DI) 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. No histologic confirmation required

• Patients with hCGbeta 51-100 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. Histologic confirmation of germinoma IS required

• Patients with germinoma of the basal ganglia and or/thalamic primary sites are eligible

• Patients with metastatic germinoma including non-contiguous disease or distant disease in the brain, ventricles, or spine are eligible

• Patients with germinoma admixed with mature teratoma are eligible

• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age

• Patients must have eligibility confirmed by Rapid Central Imaging Review performed on APEC14B1-CNS

• Imaging studies must be obtained within 31 days prior to study enrollment and start of protocol therapy. (Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI that must be obtained within 31 days prior to enrollment.)

• Patients must have a cranial magnetic resonance imaging (MRI) with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post-operative brain 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 brain MRI is recommended but not required

• Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment

• Patients must be enrolled, and protocol therapy must begin, no later than 31 days after definitive surgery or clinical diagnosis, whichever is later

• Patients must have eligibility confirmed by Rapid Central Tumor Marker Review performed on APEC14B1-CNS

• Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery. Of note, lumbar CSF should not be performed prior to obtaining spine MRI, as this can make interpretation of the spine MRI less clear

• Patients must have CSF tumor markers obtained prior to study 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. Ideally serum and CSF tumor markers should be collected at the same time and processed without delay

• For patients with solid tumors: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (Must be performed within 7 days prior to enrollment unless otherwise indicated)

• For patients with solid tumors: Platelet count \>= 100,000/uL (transfusion independent) (Must be performed within 7 days prior to enrollment unless otherwise indicated)

• For patients with solid tumors: Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (Must be performed within 7 days prior to enrollment unless otherwise indicated)

• For pediatric patients (age 3-17 years): A serum creatinine based on age/gender as follows (Must be performed within 7 days prior to enrollment unless otherwise indicated):

‣ Age: 3 to \< 6 years; maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female)

⁃ Age: ≥ 17 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female) OR a 24-hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 OR a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).

⁃ Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility.

⁃ For adult patients (age 18 years or older) (Must be performed within 7 days prior to enrollment unless otherwise indicated):

∙ Creatinine clearance ≥ 70 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (Must be performed within 7 days prior to enrollment unless otherwise indicated)

• Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase \[ALT\]) ≤ 135 U/L (Must be performed within 7 days prior to enrollment unless otherwise indicated)

‣ Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L

• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination

• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled

• CNS toxicity =\< grade 2

• Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load are eligible for this study

Locations
United States
Alabama
USA Health Strada Patient Care Center
RECRUITING
Mobile
Arkansas
Arkansas Children's Hospital
RECRUITING
Little Rock
Arizona
Phoenix Childrens Hospital
RECRUITING
Phoenix
California
Loma Linda University Medical Center
RECRUITING
Loma Linda
Children's Hospital Los Angeles
RECRUITING
Los Angeles
UCSF Benioff Children's Hospital Oakland
RECRUITING
Oakland
Children's Hospital of Orange County
RECRUITING
Orange
Lucile Packard Children's Hospital Stanford University
RECRUITING
Palo Alto
Rady Children's Hospital - San Diego
RECRUITING
San Diego
UCSF Medical Center-Mission Bay
RECRUITING
San Francisco
Colorado
Children's Hospital Colorado
RECRUITING
Aurora
Washington, D.c.
Children's National Medical Center
RECRUITING
Washington D.c.
Delaware
Alfred I duPont Hospital for Children
RECRUITING
Wilmington
Florida
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
RECRUITING
Hollywood
Nemours Children's Clinic-Jacksonville
RECRUITING
Jacksonville
Nicklaus Children's Hospital
RECRUITING
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
Arnold Palmer Hospital for Children
RECRUITING
Orlando
Nemours Children's Hospital
RECRUITING
Orlando
Nemours Children's Clinic - Pensacola
RECRUITING
Pensacola
Sacred Heart Hospital
SUSPENDED
Pensacola
Johns Hopkins All Children's Hospital
RECRUITING
St. Petersburg
Georgia
Children's Healthcare of Atlanta - Arthur M Blank Hospital
RECRUITING
Atlanta
Iowa
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
Idaho
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Illinois
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
Loyola University Medical Center
RECRUITING
Maywood
Kentucky
Norton Children's Hospital
RECRUITING
Louisville
Massachusetts
Dana-Farber Cancer Institute
RECRUITING
Boston
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
Michigan
C S Mott Children's Hospital
RECRUITING
Ann Arbor
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
RECRUITING
Grand Rapids
Minnesota
University of Minnesota/Masonic Cancer Center
RECRUITING
Minneapolis
Mayo Clinic in Rochester
RECRUITING
Rochester
Missouri
Children's Mercy Hospitals and Clinics
RECRUITING
Kansas City
Cardinal Glennon Children's Medical Center
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
Mississippi
University of Mississippi Medical Center
RECRUITING
Jackson
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
Wake Forest University Health Sciences
RECRUITING
Winston-salem
North Dakota
Sanford Broadway Medical Center
RECRUITING
Fargo
Nebraska
Children's Hospital and Medical Center of Omaha
RECRUITING
Omaha
University of Nebraska Medical Center
RECRUITING
Omaha
New Hampshire
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
RECRUITING
Lebanon
New Jersey
Hackensack University Medical Center
RECRUITING
Hackensack
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
RECRUITING
New Brunswick
Newark Beth Israel Medical Center
RECRUITING
Newark
Saint Joseph's Regional Medical Center
RECRUITING
Paterson
New York
Albany Medical Center
RECRUITING
Albany
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Mount Sinai Hospital
RECRUITING
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
State University of New York Upstate Medical University
RECRUITING
Syracuse
Montefiore Medical Center - Moses Campus
RECRUITING
The Bronx
Ohio
Rainbow Babies and Childrens Hospital
RECRUITING
Cleveland
Nationwide Children's Hospital
RECRUITING
Columbus
Oregon
Oregon Health and Science University
RECRUITING
Portland
Pennsylvania
Children's Hospital of Philadelphia
RECRUITING
Philadelphia
Saint Christopher's Hospital for Children
RECRUITING
Philadelphia
Children's Hospital of Pittsburgh of UPMC
RECRUITING
Pittsburgh
Rhode Island
Rhode Island Hospital
RECRUITING
Providence
South Carolina
Prisma Health Richland Hospital
RECRUITING
Columbia
South Dakota
Sanford USD Medical Center - Sioux Falls
RECRUITING
Sioux Falls
Tennessee
Saint Jude Children's Research Hospital
RECRUITING
Memphis
Texas
Dell Children's Medical Center of Central Texas
RECRUITING
Austin
Driscoll Children's Hospital
RECRUITING
Corpus Christi
Medical City Dallas Hospital
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
RECRUITING
Houston
M D Anderson Cancer Center
RECRUITING
Houston
Children's Hospital of San Antonio
RECRUITING
San Antonio
University of Texas Health Science Center at San Antonio
RECRUITING
San Antonio
Utah
Primary Children's Hospital
RECRUITING
Salt Lake City
Virginia
University of Virginia Cancer Center
RECRUITING
Charlottesville
Children's Hospital of The King's Daughters
RECRUITING
Norfolk
Washington
Seattle Children's Hospital
RECRUITING
Seattle
Providence Sacred Heart Medical Center and Children's Hospital
RECRUITING
Spokane
Wisconsin
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Other Locations
Australia
John Hunter Children's Hospital
RECRUITING
Hunter Regional Mail Centre
Royal Children's Hospital
RECRUITING
Parkville
Sydney Children's Hospital
RECRUITING
Randwick
Queensland Children's Hospital
RECRUITING
South Brisbane
The Children's Hospital at Westmead
RECRUITING
Westmead
Canada
University of Alberta Hospital
RECRUITING
Edmonton
IWK Health Centre
RECRUITING
Halifax
McMaster Children's Hospital at Hamilton Health Sciences
RECRUITING
Hamilton
Children's Hospital
RECRUITING
London
Centre Hospitalier Universitaire Sainte-Justine
RECRUITING
Montreal
The Montreal Children's Hospital of the MUHC
RECRUITING
Montreal
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
RECRUITING
Québec
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
RECRUITING
Sherbrooke
Hospital for Sick Children
RECRUITING
Toronto
Time Frame
Start Date: 2024-10-22
Estimated Completion Date: 2033-11-04
Participants
Target number of participants: 240
Treatments
Experimental: Stratum I (carboplatin, etoposide, 3D-CRT, IMRT, surgery)
See Detailed Description.
Experimental: Stratum II (carboplatin, etoposide, 3D-CRT, IMRT)
Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with localized germinoma achieving PR with normalization of markers who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.
Experimental: Stratum III (carboplatin, etoposide, 3D-CRT, IMRT)
Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with localized germinoma with normalization of markers who fail to achieve CR or PR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.
Experimental: Stratum IV (carboplatin, etoposide, 3D-CRT, IMRT, surgery)
Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with metastatic germinoma achieving CR undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients with metastatic germinoma and normalization of markers who fail to achieve CR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.
Experimental: Stratum V (carboplatin, etoposide, 3D-CRT, IMRT)
Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with metastatic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.
Experimental: Stratum VI (carboplatin, etoposide, 3D-CRT, IMRT, surgery)
Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with basal ganglia and thalamic germinoma achieving CR undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients with basal ganglia and thalamic germinoma and normalization of markers who fail to achieve CR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.
Experimental: Stratum VII (carboplatin, etoposide, 3D-CRT, IMRT)
Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with basal ganglia and thalamic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.
Related Therapeutic Areas
Sponsors
Leads: Children's Oncology Group

This content was sourced from clinicaltrials.gov