Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Uterine Neoplasms

Endometrial Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endometrial cancer patients who have two or more molecular features

Just obsrevation following standard of care (including surgery, chemotherapy and radiation when appropriate)

Observation only

Giorgio Bogani

Endometrial cancer is not a single entity but rather a very heterogeneous group of diseases. Historically, endometrial cancer patients have been classified as endometrioid (type I) or non-endometrioid (type II) according to the dualistic Bokhman model- However, this approach has been limited in accurately predicting prognosis and guiding treatment owing to heterogeneity within subtypes, inadequate incorporation of molecular and genetic information, and high interobserver variability .

In the last ten years, after the publication of The Cancer Genome Atlas (TCGA)\[5\], the molecular classification of endometrial cancer into four molecular subtypes \[(i) POLE/ultramutated group (POLE mutated), (ii) mismatch repair deficiency/microsatellite-instable, hypermutated group (MMRd/MSI-H), (iii) copy-number-high, TP53-mutant (CNH/p53abn), and (iv) copy-number-low, TP53-wild-type (CNL, or No Specific Mutational Profile \[NSMP\])\] has rapidly gained interest. Recently, the European Societies of Gynaecological Oncology, Radiotherapy and Oncology, and Pathology (ESGO-ESTRO-ESP), the European Society of Medical Oncology (ESMO), the National Comprehensive Cancer Network (NCCN), and the new 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system have promoted the use of (surrogate) molecular classification. Retrospective studies supported the value of adopting molecular classification to offer reliable data on prognostication and adjuvant treatment decisions. Although no prospective data are available, current guidelines promote the use of molecular profiles to tailor adjuvant treatment after surgery. As only a few retrospective studies have investigated the association between molecular profiles and response to various adjuvant treatments, it is important to note that data are limited. Interestingly, the growing adoption of molecular profiling led to the detection of a subgroup of tumors called multiple classifiers, characterized by multiple (two or three) molecular features. According to the guidelines, tumors with a POLE mutation should be considered POLEmut, regardless of other molecular features, whereas MMRd/MSI-H tumors with a p53 abnormality should be considered MMRd/MSI-H. Data on these patients is limited and fragmentary. The aforementioned consensus is based solely on a large retrospective cohort of multiple classifiers collected by Leon-Castillo et al.. Hence, to fill this literature gap, the investigators designed this retrospective study, which aimed to collect multiple classifiers patients to improve knowledge on this emerging category.

A Retrospective Study on Multiple Classifier Endometrial Cancer

Multiple Classifier Endometrial Cancer

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphoid

Cardiotoxicity

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Observation only. Patients newly diagnosed with acute leukemia who are scheduled to start treatment with chemotherapy will be enrolled and followed serially with blood collection, echocardiogram, arterial applanation tonometry, and questionnaires for 1 year.

No intervention, observational study only

observation only

Marielle Scherrer-Crosbie, MD, PhD

An observational, prospective study to describe the rates and predictors of cardiovascular events in patients with acute leukemia.

Patients recently diagnosed with acute leukemia and who will initiating chemotherapy will be enrolled and followed serially with blood collection, echocardiogram, arterial applanation tonometry, and questionnaires for 1 year.

Cardiovascular Function in Acute Leukemia

Cardiovascular Function in Leukemia Patients: an Observational Prospective Study

defined as a reduction in Left Ventricular Ejection Fraction of more than 10 percentage points from baseline and to less than 50%.

Abramson Cancer Center at Penn Medicine

Infections

Skin and Connective Tissue Diseases

Herpes Simplex

Communicable Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Lymphadenopathy

Hyperplasia

Virus Diseases

Sarcoma, Kaposi

Castleman Disease

Kaposi Sarcoma

Unicentric Castleman Disease

Multicentric Castleman Disease

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Lenograstim

Bortezomib

Sirolimus

Etoposide phosphate

Valganciclovir

Interferons

Ganciclovir

Ganciclovir triphosphate

Interferon-alpha

Zidovudine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

Clotrimazole

Miconazole

Antifungal Agents

Antimetabolites

Reverse Transcriptase Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

Patients not responding to high- dose zidovudine and valganciclovir alone may be treated with botezomib plus high- dose zidovudine and valganciclovir

Single agent sirolimus for patients where targeted oncolytic virotherapy seems suboptimal

EPOCH chemotherapy with rituximab may be utilized to rescue such patients, with the intent of stabilizing suchpatients

Rituximab with liposomal doxorubicin (R-Dox) followed by consolidation or lmaintenancel therapy with dose escalating interferon-alpha

Etoposide 50 mg/m2 /day continuous intravenous infusion (CIVI) over 24 hours x 4 days (days 1-4) of 21 day cycle. A maximum of 6 cycles of R-EPOCH-R will be administered except in exceptional circumstances.

Ages 18 and over: Initial dose of 7.5 million units subcutaneous, three times weekly x 14 days; subsequent dosesincrease dose as tolerated each 14 days to a maximum of 45 million units subcutaneous three times weekly; Ages 12-17: Initial dose of 5 million units/m2 subcutaneous, three times weekly x 14 days Subsequent doses: Increase dose as tolerated each 14 days to a maximum of 30 million units/m2 subcutaneous, three times weekly

Rituximab 375 mg/m2 IV day 1, shall be administered prior to Doxil injection. When combined with EPOCH chemotherapy, Rituximab will be given on days 1 and 5.

Cycle 1: Zidovudine 600 mg PO QID x 7-21 days in outpatient setting;600 mg PO q6hours x 7-21 (Intravenous zidovudine 300 mg q 6 hours may be substituted) days for inpatients; Cycle 2 and beyond: 600 mg PO QID x 7 days in outpatient setting; 600 mg PO q 6 hours x 7 days (300 mg q 6 hours may be substituted)

21 day cycle; 20 mg/m2 Liposomal Doxorubicin given on day 1 and shall be administered after completion of Rituximab infusion from 2 to 6 cycles.

Liposomal Doxorubicin

1.3 mg/m2 IV days 1, 4, 8, and 11. Cycle length is 21 days.

Cycle 1: Valganciclovir 900 mg PO BID x 7-21 days in outpatient setting; 900 mg PO q 12 hours x 7-21 days for inpatients; Cycle 2 and beyond: 900 mg PO BID x 7 days for outpatients; 900 mg PO q 12 hours x 7 days (Intravenous ganciclovir 5 mg/kg may be substituted) for inpatients

10 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.

0.4 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.

Cyclophosphamide: if CD4 \< 100 cells/mm3, 187 mg/m2 IV (Day 5) if CD4 greater than or equal to 100 cells/mm3, 375 mg/m2 IV (Day 5) of 21 day cycle.

Filgrastim 300 micrograms subcutaneous daily beginning day 6 until absolute neutrophil count recovery 5000 cells/mm3 (Pegfilgrastim may be substituted with PI approval, at the recommended dose of one 6mg syringe)

Filgrastim (G-CSF)

Prednisone 60 mg/m2/day PO x 5 days (days 1-5)of 21 day cycle.

Maximum daily dose of 40 mg given as a single agent on 21 day cycle.

Observation Only

Robert Yarchoan, M.D.

This study will gain information about a rare disorder called KSHV-associated multicentric Castleman s disease (MCD). KSHV, a virus, causes several kinds of cancer, including some forms of MCD. KSHV stands for the Kaposi s sarcoma herpes virus, also called human herpes virus-8, or HHV-8. Researchers want to understand the biology of KSHV-MCD to identify how this disease causes illness and to find ways to treat it. There is no standard therapy effective for all cases of KSHV-MCD. The disease is often fatal, and about half the people who have it die within 2 years of diagnosis.

Participants ages 18 and older may be eligible for this study. Participation entails more drawing of blood and having repeated tumor biopsies than if patients received treatment in a non-research setting. Researchers would like to learn more about the relationship of KSHV and Castleman s disease symptoms, and they want to obtain at least three biopsies in this study.

There are some side effects of experimental therapy that participants may take for KSHV-MCD. Zidovudine, or Retrovir , is used at a high dose. It is given orally or through a vein, four times daily, for 7 days or longer. Zidovudine can cause nausea, vomiting, decreased bone marrow function, and decreased blood counts. Combined with valganciclovir, or Valcyte , it is likely to be more toxic to bone marrow. Valganciclovir can cause problems with bone marrow function, leading to low blood counts, sterility, and defects in a fetus. Combined with zidovudine, valganciclovir may cause more toxicity to the bone marrow. It is given twice daily for 7 days or longer. Bortezomib, or Velcade , is given for a few seconds by a rapid push through a needle into the vein. It is given twice weekly for four doses and then stopped for 1 week. Bortezomib can sometimes cause low blood pressure; it also can cause gastrointestinal problems and a low blood platelet count. Rituximab and liposomal doxorubicin are drugs given by a catheter into a vein. Interferon-alpha is given by injection into the skin. Those drugs are not experimental, but their use in Castleman s disease is experimental.

Some participants may be treated with a combination of chemotherapy followed by interferon-alpha. Interferon-alpha is infected into the skin by a needle. The natural form of interferon is produced by the body and helps to control viral infections. KSHV decreases the effect of the body s interferon, and the researchers want to see if giving higher doses of interferon will help to control KSHV infection.

A positron emission tomography (PET) scan, for research purposes only, may be done up to three times a year. A radioactive sugar molecule called fluorodeoxyglucose, or FDG, is used. It is believed that activated lymphocytes that may be found in participants disease might use more FDG because these cells burn more glucose fuel.

This study may or may not have a direct benefit for participants. However, detailed assessments made throughout the study may provide information to help the doctors treat KSHV-MCD better.

Background:

* Multicentric Castleman's disease (MCD) is a rare but lethal Kaposi's sarcoma-associated herpesvirus (KSHV) associated lymphoproliferative disorder with a median survival of 2 years. It occurs more often in HIV-infected individuals than those without HIV infection. The poor prognosis is not fully explained by the underlying HIV, as the HIV-negative cases appear to have no survival advantage over the HIV-positive cohort. The disease has no defined standard treatment and has not been prospectively studied in a comprehensive manner.
* KSHV-MCD may provide a model for the development of targeted oncolytic virotherapy or other pathogenesis-based approaches to viral-associated malignancies. In KSHV-MCD, viral encoded tyrosine kinase genes appear to be possible targets to exploit in a virotherapy approach. Specific viral encoded genes appear to convert zidovudine and ganciclovir (or valganciclovir) into toxic phosphorylated moieties within the KSHV-infected tumor cells, to specifically target the KSHV-infected cells thus leading to specific cell death. If successful, this could have direct therapeutic benefit to participants and also provide a model for further development of this approach in other tumors.

Objectives

-To study and describe the natural history of KSHV-MCD.

Eligibility

* Age greater than or equal to 18 years
* Biopsy proven KSHV-associated MCD

Design

* Natural History study
* Inclusion of treatment as needed, with guidelines for preliminary investigation of a variety of specific treatments of interest

  * High-dose zidovudine and ganciclovir
  * High-dose zidovudine and ganciclovir and bortezomib
  * Sirolimus
  * Rituximab with liposomal doxorubicin followed by interferon-alpha
  * Rituximab with EPOCH chemotherapy

Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity

Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity

percentage of patients alive until study closure

Quantify the number of flares requiring treatment in patients enrolled in this study

National Cancer Institute (NCI)

This study will gain information about a rare disorder called KSHV-associated multicentric Castleman s disease (MCD). KSHV, a virus, causes several kinds of cancer, including some forms of MCD. KSHV stands for the Kaposi s sarcoma herpes virus, also called human herpes virus-8, or HHV-8. Researchers want to understand the biology of KSHV-MCD to identify how this disease causes illness and to find ways to treat it. There is no standard therapy effective for all cases of KSHV-MCD. The disease is often fatal, and about half the people who have it die within 2 years of diagnosis.

Participants ages 18 and older may be eligible for this study. Participation entails more drawing of blood and having repeated tumor biopsies than if patients received treatment in a non-research setting. Researchers would like to learn more about the relationship of KSHV and Castleman s disease symptoms, and they want to obtain at least three biopsies in this study.

There are some side effects of experimental therapy that participants may take for KSHV-MCD. Zidovudine, or Retrovir , is used at a high dose. It is given orally or through a vein, four times daily, for 7 days or longer. Zidovudine can cause nausea, vomiting, decreased bone marrow function, and decreased blood counts. Combined with valganciclovir, or Valcyte , it is likely to be more toxic to bone marrow. Valganciclovir can cause problems with bone marrow function, leading to low blood counts, sterility, and defects in a fetus. Combined with zidovudine, valganciclovir may cause more toxicity to the bone marrow. It is given twice daily for 7 days or longer. Bortezomib, or Velcade , is given for a few seconds by a rapid push through a needle into the vein. It is given twice weekly for four doses and then stopped for 1 week. Bortezomib can sometimes cause low blood pressure; it also can cause gastrointestinal problems and a low blood platelet count. Rituximab and liposomal doxorubicin are drugs given by a catheter into a vein. Interferon-alpha is given by injection into the skin. Those drugs are not experimental, but their use in Castleman s disease is experimental.

Some participants may be treated with a combination of chemotherapy followed by interferon-alpha. Interferon-alpha is infected into the skin by a needle. The natural form of interferon is produced by the body and helps to control viral infections. KSHV decreases the effect of the body s interferon, and the researchers want to see if giving higher doses of interferon will help to control KSHV infection.

A positron emission tomography (PET) scan, for research purposes only, may be done up to three times a year. A radioactive sugar molecule called fluorodeoxyglucose, or FDG, is used. It is believed that activated lymphocytes that may be found in participants disease might use more FDG because these cells burn more glucose fuel.

This study may or may not have a direct benefit for participants. However, detailed assessments made throughout the study may provide information to help the doctors treat KSHV-MCD better.

...

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Retrospective Study on Multiple Classifier Endometrial Cancer	NCT05976113	Uterine Cancer	Observation onl...	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Cardiovascular Function in Acute Leukemia	NCT03760237	Leukemia, Myelo... Leukemia, Lymph... Cardiotoxicity	observation onl...	18 Years - 90 Years	Abramson Cancer Center at Penn Medicine
Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity	NCT00092222	Lymphoprolifera... HHV-8 Malignancy HIV	Etoposide Interferon-alph... Rituximab Zidovudine Liposomal Doxor... Bortezomib Valganciclovir Doxorubicin Vincristine Cyclophosphamid... Filgrastim (G-C... Prednisone Sirolimus Observation Onl...	18 Years -	National Institutes of Health Clinical Center (CC)
A Retrospective Study on Multiple Classifier Endometrial Cancer	NCT05976113	Uterine Cancer	Observation onl...	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity	NCT00092222	Lymphoprolifera... HHV-8 Malignancy HIV	Etoposide Interferon-alph... Rituximab Zidovudine Liposomal Doxor... Bortezomib Valganciclovir Doxorubicin Vincristine Cyclophosphamid... Filgrastim (G-C... Prednisone Sirolimus Observation Onl...	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for observation only