Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Endodermal Sinus Tumor

Teratoma

Germinoma

Carcinoma, Embryonal

Choriocarcinoma

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Trophoblastic Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

Germ Cells Tumors

Central Nervous System Germinoma

Embryonal Carcinoma

Testicular Yolk Sac Tumor

Children and adolescents with a germ cell tumor, previously enrolled on APEC14B1 or AEPI10N1 who allow access to medical records (including audiograms), grant permission to: evaluate of all of their DNA, place their genetic and health information in scientific databanks, and collect a blood sample at a routine clinic/home visit, as well as complete a questionnaire about your health and quality of life since treatment.

Questionnaire provide to participant's about their health and quality of life since treatment

Questionnaire Administration

Tumor DNA requested from the Biopathology Center

Tumor Specimen Collection

Germline DNA specimens requested from the Biopathology Center or newly collected saliva

Germline DNA Samples

Blood Sample Collection

Jenny Poynter, PhD

A Non-Therapeutic Study that aims to establish a cohort of GCT survivors to understand short term and long-term adverse effects of treatment and to conduct molecular analyses to improve risk stratification.

PRIMARY OBJECTIVES:

I. Establish a survivorship cohort for pediatric and adolescent GCT comprised of participants from AEPI10N1 and APEC14B1 to assess short term and long-term adverse events associated with GCT treatment.

II. Compare somatic variation by tumor histology to identify molecular signatures that improve prognostic risk stratification.

III. Identify methylation patterns that predict poor clinical outcomes, including disease relapse and death.

OUTLINE:

Medical records from pediatric and adolescent Germ Cell Tumor (GCT) participants from AEPI10N1 and APEC14B1 will be used to obtain treatment information and validate self-reported outcomes. Paired normal and tumor samples will be used to evaluate single nucleotide variants, indels, copy number variations, and DNA methylation patterns. Ototoxicity will be determined by central review of audiogram files obtained from the treating institutions and self-reported based on questionnaire data.

* Tumor Specimen Collection
* Germline DNA Samples (saliva)
* Blood Sample Collection (serum/plasma)

Molecular Epidemiology of Pediatric Germ Cell Tumors

Pediatric Germ Cell Tumors: Outcomes, Genomics and Epigenetics

Ototoxicity as determined by central review of end of therapy audiograms will serve as the primary outcome variable for analyses. Current ototoxicity will be assessed using an app-based hearing assessment. For the app-based audiometry assessment, unilateral hearing loss will be defined as at least one pure tone threshold greater than 25 decibels across at any one of the frequencies from 2,000 Hz- 8,000 Hz to align with the SIOP Boston guidelines, while bilateral hearing loss will be defined as a pure tone threshold \> 25 decibels in both ears at any one of the frequencies.

Compare somatic variation by tumor histology to identify molecular signatures that improve prognostic risk stratification. Somatic mutations will be identified by comparing tumor samples to normal samples. Risk stratification will be based on event free survival, defined as the time from diagnosis to relapse or death.

Compare the association between DNA methylation patterns and relapse or death. Mixed-effects regression models will be used to test for association between methylation beta values and poor outcomes. The outcome will be defined as a binary variable with a value of one if the patient experienced a relapse or death event and zero otherwise.

Children's Oncology Group

Gland and Hormone Related Diseases

Testicular Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Intravenous Brentuximab Vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity

Alessandro M Gianni, MD

Roberto Salvioni, MD

Andrea Necchi, MD

The purpose of the study is to assess the activity of Brentuximab vedotin in refractory germ cell tumors.

Complete responses with third-line or later salvage chemotherapy (CT) for germ cell tumors (GCT) range 0% to 10% and are usually short-lived and nearly all patients (pts) progressing after multiple courses or high-dose CT will ultimately die from progressive disease.

Cluster of Differentiation antigen-30 (CD30) is expressed by untreated embryonal carcinoma (ECA) thus lending support to a rationale for a targeted approach. The investigators retrospectively re-assessed ECA to strongly retain CD30 staining in most cases (\>70%), even after multiple courses or high-dose CT. Moreover, a negative prognostic value of CD30 expression by residuals after CT, particularly in the salvage setting, was set. Brentuximab vedotin is an antibody-drug conjugate consisting of the chimeric anti-CD30 antibody chemically conjugated to an antitubulin synthetic analog (MMAE).

Proof of activity will provide rationale for developing first-line chemo-immunotherapy or maintenance immunotherapy for selected high-risk pts. The primary objective of the study will be the activity of Brentuximab vedotin in refractory GCT. Secondary objectives will include safety and survival.

24 pts with biopsy-proven CD30 positive GCT will receive intravenous Brentuximab vedotin at the dose of 1.8 mg/Kg every 3 weeks until disease progression or onset of unacceptable toxicity. Further eligibility requirements will include failure of 2 or 3 platinum-based CT (prior high-dose CT is allowed). All pts will undergo measurement of serum tumor markers, a computed tomography and a positron emission tomography (PET) scan every weeks. An optimal Simon's 2-stage design will be applied. The primary endpoint is the objective response-rate (ORR). An ORR of 5% is not promising, while a 25% rate will be promising. In stage 1, 9 evaluable patients will be accrued. The type I and II error are both set at 10%.

Additional post-treatment tissue will be available for pts undergoing surgery in the treatment time-course. Tissue array blocks will be constructed from samples of all pts. Assessment will include mutational analysis of most-frequently mutated genes. Two serum aliquots will be collected at baseline and during/end of treatment to assess circulating CD30.

Brentuximab Vedotin (SGN-35) as Salvage Treatment for CD30-positive Germ Cell Tumors

Brentuximab Vedotin (SGN-35) as Salvage Therapy for Males With Advanced and Platinum-resistant Germ-cell Tumors. An Open Label, Single Group, Phase 2 Trial.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Millennium Pharmaceuticals, Inc.

Fondazione Michelangelo

Nervous System Diseases

Brain Neoplasms

Pineal Germ Cell Tumor

Nonseminomatous Germ Cell Tumor

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Carboplatin

Etoposide

Cyclophosphamide

Ifosfamide

Lenograstim

Etoposide phosphate

Podophyllotoxin

Thiotepa

Levonorgestrel

Isophosphamide mustard

Mesna

Mechlorethamine

Enzyme Inhibitors

Adjuvants, Immunologic

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Protective Agents

Keratolytic Agents

Tubulin Modulators

Antimitotic Agents

Undergo collection of CSF and blood samples

Biospecimen Collection

Filgrastim

Magnetic Resonance Imaging

Pegfilgrastim

Peripheral Blood Stem Cell Transplantation

Radiation Therapy

Second-Look Surgery

Site Public Contact

Brenda J. Wittman

Joseph C. Torkildson

Lindsey M. Hoffman

Holly E. Pariury

David L. Becton

Hung N. Tran

Albert Kheradpour

Jacqueline N. Casillas

Tom B. Davidson

Fataneh (Fae) Majlessipour

Karen S. Fernandez

Aarati V. Rao

Elyssa M. Rubin

William D. Roberts

Alyssa T. Reddy

Kathleen M. Dorris

Michael S. Isakoff

Scott M. Bradfield

Jeffrey S. Dome

Emad K. Salman

William B. Slayton

Ziad A. Khatib

Jaime M. Libes-Bander

Stacie L. Stapleton

Don E. Eslin

Jason R. Fangusaro

Wade T. Kyono

Martha M. Pacheco

Dipti S. Dighe

Eugene Suh

Prerna Kumar

Sandeep Batra

Samantha L. Mallory

David S. Dickens

Ashok B. Raj

Craig Lotterman

Daniel L. Callaway

Stanley Chaleff

Jason M. Fixler

Kenneth J. Cohen

Shannon M. MacDonald

Kee Kiat Yeo

Andrea T. Franson

Stephanie A. Toll

Laura E. Agresta

Kathleen J. Yost

Laura K. Gowans

Michael K. Richards

Jonathan D. Schwartz

Betty L. Herrington

Barbara A. Gruner

Keith J. August

William S. Ferguson

Mohamed S. Abdelbaki

Robin D. Hanson

Jill C. Beck

Alan K. Ikeda

Derek R. Hanson

Kathryn L. Laurie

Nibal A. Zaghloul

Scott Moerdler

Alissa Kahn

Lauren R. Weintraub

Alice Lee

Mahmut Y. Celiker

Mark P. Atlas

Sharon L. Gardner

Sameer Farouk Sait

Laura E. Hogan

Melanie A. Comito

Jessica C. Hochberg

Joel A. Kaplan

Jessica M. Sun

Andrea R. Whitfield

Thomas W. McLean

Samuel J. Milanovich

Erin Wright

Trent R. Hummel

Duncan S. Stearns

Rabi Hanna

Mark A. Ranalli

Mukund G. Dole

Jamie L. Dargart

Rene Y. McNall-Knapp

Jason M. Glover

Linda C. Stork

Jacob A. Troutman

Jagadeesh Ramdas

Shannon M MacDonald

This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, 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 or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.

PRIMARY OBJECTIVES:

I. To monitor outcome to ensure that children and young adults with localized central nervous system (CNS) non-germinomatous germ cell tumors (NGGCT) treated with induction chemotherapy followed by response evaluation and whole ventricular + spinal canal irradiation (WVSCI) will maintain the excellent 2-year progression free survival (PFS) rate as compared to ACNS0122 (NCT00047320).

II. To improve disease control by decreasing the number of spinal relapses for patients who achieve a complete response (CR) or partial response (PR) and receive WVSCI as compared to whole ventricular radiation on ACNS1123 (NCT01602666).

SECONDARY OBJECTIVES:

I. To estimate the response rates to induction chemotherapy and WVSCI for localized NGGCT patients who achieve a CR/PR.

II. To estimate the PFS and overall survival (OS) for localized NGGCT patients who achieve a CR/PR and receive WVSCI.

III. To estimate the PFS and OS for patients with less than a CR/PR following Induction who subsequently receive high-dose chemotherapy with peripheral stem cell rescue (HDCSCR).

IV. To estimate the response rate for patients with less than a CR/PR following Induction who subsequently receive HDCSCR.

EXPLORATORY OBJECTIVES:

I. To prospectively compare outcomes based on radiation modality, photon versus proton, including cognitive, social and behavioral functioning, auditory, and neuro-endocrine function.

II. To compare spinal column growth and cell counts following radiation as measured by height and weight, and complete blood count (CBC) values during and after radiation therapy, based on treatment modality (photon versus \[vs.\] proton therapy) and planned inclusion/exclusion of the vertebral body in patients \< 13 years of age.

III. To compare local vs. central review recommendations for second-look surgery and document barriers for performing such surgeries as well as their clinical benefit in pediatric NGGCT.

IV. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults with localized CNS NGGCT with testing as per the Children's Oncology Group (COG) Standardized Neuropsychological and Behavioral Battery.

V. To evaluate patterns of disease recurrence/failure with respect to radiation dose distribution.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of cycles 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide IV over 60-120 minutes on days 1-5 of cycles 2, 4, and 6. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients are assigned to 1 of 2 plans (ventricular + spinal canal irradiation \[WVSCI\] or high-dose chemotherapy with peripheral stem cell rescue \[HDCSCR\]) based on response to induction chemotherapy:

* Patients who achieve radiographic CR/PR with marker normalization proceed to WVSCI. Patients who achieve radiographic CR without marker normalization proceed to HDCSCR.
* Patients who achieve less than radiographic CR/PR with marker normalization proceed to second-look surgery (unless contraindicated). If second-look surgery reveals mature teratoma or non-viable tumor, proceed to WVSCI. If second-look surgery reveals viable tumor, proceed to HDCSCR. Patients who are unable to undergo second-look surgery are removed from protocol therapy but remain on study for follow-up.
* Patients who achieve less than radiographic CR/PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.
* Patients who achieve radiographic PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.

PLAN A (WVSCI THERAPY): Within 6 weeks of the end of induction chemotherapy or second-look surgery, patients undergo WVSCI once daily (QD) for 5 days weekly (17 fractions followed by a boost dose for 13 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.

PLAN B (CONSOLIDATION THERAPY \[HDCSCR\]): Within 6-8 weeks of the end of induction chemotherapy or second-look surgery, patients receive etoposide IV and thiotepa IV over 3 hours on days -5 to -3 and undergo peripheral blood stem cell (PBSC) transplant on day 0. Patients then undergo radiation therapy QD for 5 days weekly (20 fractions followed by a boost dose for 10 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients also undergo magnetic resonance imaging (MRI), as well as collection of cerebral spinal fluid (CSF) and blood sample throughout the trial.

After completion of study treatment, patients are followed for up to 10 years.

A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT

A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor

Will be assessed by the Wechsler Preschool and Primary Scale of Intelligence 4th Edition (WPPSI-IV), Wechsler Intelligence Scale for Children 5th Edition (WISC-V), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), depending on patient's age. One-sample confidence intervals will be used to estimate mean pairwise changes in intelligence scores between 2 time points within each treatment arm.

Will be assessed by the Wechsler Preschool and Primary Scale of Intelligence 4th Edition (WPPSI- IV), Wechsler Intelligence Scale for Children 5th Edition (WISC V), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), depending on patient's age. A 2-sample confidence interval approach will be used to estimate the difference in score changes between the two cohorts (WVSCI versus HDCSCR) in order to describe differential effects of the 2 treatment strategies.

Will be assessed by the WISC-V or WAIS-IV processing speed index tasks. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within each treatment arm.

Will be assessed by the WISC-V or WAIS-IV processing speed index tasks. A 2-sample confidence interval approach will be used to estimate the difference in score changes between the two cohorts (WVSCI versus HDCSCR) in order to describe differential effects of the 2 treatment strategies.

Will be assessed by the Children's Memory Scale and California Verbal Learning Test. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.

Will be assessed by the Behavior Assessment System for Children - 3rd Edition. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.

Will be assessed by the Adaptive Behavior Assessment System - 3rd Edition. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.

Will be assessed by the Pediatric Quality of Life Inventory version 4.0. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.

Will be assessed by the Pediatric Quality of Life Inventory version 4.0. 2-sample confidence interval approach will be used to estimate the difference in score changes between the two cohorts (WVSCI versus HDCSCR) in order to describe differential effects of the 2 treatment strategies.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Epidemiology of Pediatric Germ Cell Tumors	NCT05564026	Germ Cell Tumor Germinoma Teratoma Embryonal Carci... Yolk Sac Tumor Choriocarcinoma Mixed Germ Cell... Late Effects Pediatric Germ ...	Questionnaire A... Tumor Specimen ... Germline DNA Sa... Blood Sample Co...	-	Children's Oncology Group
Brentuximab Vedotin (SGN-35) as Salvage Treatment for CD30-positive Germ Cell Tumors	NCT01851200	Germ Cell Cance...	Brentuximab Ved...	18 Years -	Fondazione Michelangelo
Molecular Epidemiology of Pediatric Germ Cell Tumors	NCT05564026	Germ Cell Tumor Germinoma Teratoma Embryonal Carci... Yolk Sac Tumor Choriocarcinoma Mixed Germ Cell... Late Effects Pediatric Germ ...	Questionnaire A... Tumor Specimen ... Germline DNA Sa... Blood Sample Co...	-	Children's Oncology Group
A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT	NCT04684368	Central Nervous... Choriocarcinoma Embryonal Carci... Immature Terato... Malignant Terat... Mixed Germ Cell... Pineal Region G... Pineal Region I... Pineal Region Y... Suprasellar Ger...	Biospecimen Col... Carboplatin Etoposide Filgrastim Ifosfamide Magnetic Resona... Mesna Pegfilgrastim Peripheral Bloo... Questionnaire A... Radiation Thera... Radiation Thera... Second-Look Sur... Thiotepa	3 Years - 29 Years	Children's Oncology Group

Spots Global Cancer Trial Database for embryonal carcinoma