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

Skin and Connective Tissue Diseases

Sarcoma

Histiocytoma, Malignant Fibrous

Histiocytoma

Neoplasms, Connective and Soft Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Concurrent anlotinib and Toripalimab therapy, with Blood Draw and Tumor Specimen Collection for correlative studies

Once a day dosing of anlotinib alone for the first 7 days, Anlotinib ( 12mg, QD, PO, d1-14, 21 days per cycle), take once when limosis in the morning. If patients cannot suffer from AEs, they can get declined dosage.

Anlotinib

Toripalimab 240mg shall be administered via intravenous (IV) infusion, once every 21 days, on day 8 and day 29 of the first cycle, and days 1 and 22 of the following cycles.

Toripalimab

Peripheral blood draws for correlative studies characterizing T-cells in peripheral blood will be performed at three timepoints: 1) pre-treatment, 2) on-treatment on cycle 3 day 1, and 3) off-study.

Blood Draw

Tumor specimen collection via core needle biopsy for correlative studies characterizing T-cells in tumor tissue will occur at three timepoints: 1) pre-treatment, 2) on-treatment on cycle 3 day 1, and 3) off-study.

Di Wu

The investigators hypothesize that combination anlotinib with toripalimab will improve progression-free survival relative to historical controls in patients with Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma.

This is a single-institution, open-label, single-arm Phase II study to determine the efficacy and safety of anlotinib in combination with Toripalimab compared with historical controls as first-line treatment in patients with Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma.

Since the primary endpoint is survival outcome, progression-free survival (PFS) sample size calculation is based on a single-arm survival design. The investigators will employ early stopping rules for lack of efficacy, based on previously reported historical controls progression-free rate at 3 months was 57% in MFH and This study predicts that as the First-Line treatment of Undifferentiated Pleomorphic Sarcoma, progression-free rate at 3 months is expected to reach more than 80%.

Patients will be treated with once a day dosing of anlotinib alone for the first 7 days, followed by concurrent anlotinib administered once a day at 12mg orally (PO), plus intravenous administration of toripalimab every 21 days. Patients will be assessed every six weeks for toxicity. After the first five patients are enrolled, the investigators will assess safety of the combination. If 2 or fewer patients exhibit dose-limiting toxicity (DLT), the investigators will then proceed with intrapatient titration of anlotinib dosing at each cycle based on the presence or absence of predefined toxicities.

Correlative studies characterizing T-cells in tumor tissue and in peripheral blood will be performed at three timepoints: 1. pre-treatment, 2. on-treatment on cycle 3 day 1, and 3. off-study. Additional exploratory imaging investigations, and assessment of circulating tumor cells are included for all patients.

Trial therapy will last until withdrawal of consent, disease progression and/or unacceptable toxicity, whichever occurs first.

Study of Anlotinib Hydrochloride and Toripalimab in Subjects With Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma

A Single-arm, Single-center Prospective Study of Anlotinib Hydrochloride and Toripalimab in Subjects With Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma Patients

The quantity of CD3+ T-cells in peripheral blood and in tumor biopsies at each timepoint (baseline, cycle 3, and off-study).

The expression category in tumor tissue (none (0%), low (\<5%), intermediate (5-50%), or high (\>50%) of PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, LAG-3 at each timepoint (baseline, cycle 3, and off-study).

The following T cell subsets will be studied in peripheral blood and tumor tissue: (CD4, CD8, T-reg, CTLA4, TIM3, LAG3, memory, naïve, PD-1, Ki67). For each marker, the absolute change in the marker(s) value will be calculated:

1. Cycle 3 marker value minus Baseline marker value
2. Progression marker value minus Cycle 3 marker value
3. Progression marker value minus Baseline marker value

Utilizing each of the alternative (non-RECIST) radiological criteria the investigators will categorize clinical benefit status (CR/PR/SD vs PD). CT and/or MRI with dynamic contrast enhanced sequences will be collected throughout the study at every disease evaluation and analyzed using Choi criteria, MRI volumetrics, and immune-related response criteria. PET/CT will be obtained at baseline, Cycle 3, and off-study and tumor response determined by Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST 1.0).

The quantity of circulating tumor cells (CTCs) in peripheral blood will be measured at three timepoints: baseline, cycle 3, and off-study.

Rate of participants who are progression-free at 3 months after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Progression-free survival (PFS) is defined as the time from treatment initiation until documented disease progression or death (by any cause, in the absence of progression).

Rate of participants who are progression-free at 6 months and 12-Month after the start of protocol therapy, using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria.

Rate of participants achieving complete response (CR) or partial response (PR) at 3, 6 and 12 months after the start of protocol therapy, according to RECIST version 1.1 criteria.

Rate of participants achieving complete response (CR), partial response (PR) or stable disease (SD) at 3, 6 and 12 months after the start of protocol therapy, according to RECIST version 1.1 criteria.

Defined as the time between the first assessment of a tumor as PR or CR and the first assessment as PD or any cause of death，according to RECIST version 1.1 criteria.

Defined as the time between participant enrollment to the first assessment of a tumor as PR or CR，according to RECIST version 1.1 criteria.

Defined as the time between participant enrollment to death or date of censoring.

Rate of dose-limiting toxicities (DLTs) and/or grade 3 or 4 serious adverse events (SAEs) in study participants up to 30 days after the end of protocol therapy. Toxicity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

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
Study of Anlotinib Hydrochloride and Toripalimab in Subjects With Unresectable or Metastatic Undifferentiated Pleomorphic Sarcoma	NCT03946943	Soft Tissue Sar... Undifferentiate...	Anlotinib Toripalimab Blood Draw Tumor Specimen ...	16 Years -	The First Hospital of Jilin University
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

Spots Global Cancer Trial Database for tumor specimen collection