Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Recurrence

Thyroid Diseases

Carcinoma, Renal Cell

Sarcoma

Osteosarcoma

Wilms Tumor

Central Nervous System Neoplasms

Sarcoma, Ewing

Nervous System Neoplasms

Adrenocortical Carcinoma

Carcinoma, Medullary

Rhabdomyosarcoma

Hepatoblastoma

Sarcoma, Alveolar Soft Part

Sarcoma, Clear Cell

Thyroid Neoplasms

Carcinoma, Neuroendocrine

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neoplasms, Connective and Soft Tissue

Endocrine System Diseases

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Myosarcoma

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Adrenal Cortex Neoplasms

Adrenal Gland Neoplasms

Adrenal Cortex Diseases

Adrenal Gland Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Soft Tissue Sarcoma

Wilms' Tumor

Ewing Sarcoma

Thyroid Cancer, Medullary

Alveolar Soft Part Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib

Given PO

Note: Capsule formulation (Cometriq) not used in this trial.

Cabozantinib S-malate

Pharmacological Study

Srivandana Akshintala

This phase II trial studies how well cabozantinib-s-malate works in treating younger patients with sarcomas, Wilms tumor, or other rare tumors that have come back, do not respond to therapy, or are newly diagnosed. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth and tumor blood vessel growth.

PRIMARY OBJECTIVES:

I. To determine the objective response rate (complete response + partial response) of cabozantinib-s-malate (XL184) in children and young adults with Ewing sarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, and Wilms tumor.

II. To estimate whether XL184 therapy either improves the disease control rate at 4 months in patients with recurrent measurable osteosarcoma as compared to a historical Childrens Oncology Group (COG) experience or produces an objective response rate.

SECONDARY OBJECTIVES:

I. To further define XL184 related toxicities in pediatric, adolescent and young adult patients.

II. To further define XL184 pharmacokinetics in the pediatric and adolescent patients.

III. To estimate 1-year time to progression, progression free survival (PFS) and overall survival for each stratum, and if feasible to compare to historical controls.

EXPLORATORY OBJECTIVES:

I. To assess the effect of XL184 on patients' immune cell subsets. II. To obtain tumor tissue (snap frozen, formalin-fixed and paraffin-embedded \[FFPE\] blocks, or unstained slides) from diagnosis, recurrence, or both, for possible future studies.

OUTLINE:

Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 6 months for 1 year and then annually for up to 5 years.

Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

Phase 2 Trial of XL184 (Cabozantinib) an Oral Small-Molecule Inhibitor of Multiple Kinases, in Children and Young Adults With Refractory Sarcomas, Wilms Tumor, and Other Rare Tumors

The association between the host immune system and response to cabozantinib-s-malate will be assessed in an exploratory manner. each biomarker will be correlated with the clinical outcomes of objective response and progression free survival.

Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Response rates will be calculated as the percent of evaluable patients who are responders (Overall Best Response of Partial Response or Complete Response), and confidence intervals will be constructed accounting for the two-stage design.

Will be assessed by the Response Evaluation Criteria in Solid Tumors version 1.1 and Disease Control (see section 9.3.2 of the ADVL1622 Protocol). Response + Disease Control rate will be calculated as the percent of evaluable patients who are responders or who met the definition of disease control, and confidence intervals will be constructed accounting for the two-stage design.

Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy

Day 1 PK peak concentration will be summarized by the mean and the standard deviation.

Day 1 PK time to peak concentration will be summarized by the mean and the standard deviation.

Day 1 PK area under the curve will be summarized by the mean and the standard deviation.

PK accumulation will be summarized by the mean and the standard deviation.

PK half-life will be summarized by the mean and the standard deviation.

Percent of patients not yet progressed at 1 year as estimated by the Kaplan-Meier method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Clinical progression was also counted as an event for this analysis.

The 1-year Progression Free Survival will be estimated using Kaplan-Meier methodology. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.1), as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

The 1-year Overall Survival will be estimated using Kaplan-Meier methodology.

National Cancer Institute (NCI)

Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.

Patients receive cabozantinib-s-malate (XL184), 40mg/m2/day orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ewing's Sarcoma

Non-Rhabdomyosarcoma Soft Tissue Sarcoma

Rare Tumors

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Results Reporting Coordinator

All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol in non-osteosarcoma strata which were either statistical strata (Ewing's Sarcoma, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, and Rare Tumors) or accrued enough patients to be analyzed (Wilms Tumor). Data is limited for Rare tumors due to low accrual.

Objective Response (Non-Osteosarcoma Strata)

All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol in the osteosarcoma stratum.

Objective Response (Osteosarcoma Stratum)

All patients who met the evaluable for toxicity criteria outlined in section 9.5 of the ADVL1622 protocol.

Percentage of Participants With Adverse Events

All Pharmacokinetic Patients

All patients who consented to PK or were required to consent to PK and had enough samples to estimate the PK Parameter of interest.

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Cmax

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Tmax

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: AUC

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Accumulation

Pharmacokinetics (PK) Parameters of Cabozantinib S-malate: Half-life

All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol.

Time to Progression (TTP)

Progression Free Survival (PFS)

Overall Survival (OS)

Change in Immune Biomarkers

Overall Study

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Hematinics

Pembrolizumab

Poly I-C

Liver Extracts

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1 of odd number cycles. Patients also receive BO-112 by intratumoral injection on day 1, 8, and 15 of cycle 1, and day 15 of subsequent cycles. Treatment repeats every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

Nanoplexed Poly I:C BO-112

Richard S Finn

This early phase I trial evaluates the side effects of BO-112 and pembrolizumab and how well they work in treating patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C liver cancer. Immunotherapy with BO-112, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving BO-112 and pembrolizumab may help treat patients with liver cancer.

PRIMARY OBJECTIVE:

I. To determine the early efficacy and safety for the combination of intratumoral nanoplexed poly I:C BO-112 (BO-112) in combination with pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) who have progressed on prior anti-PD-1/PD-L1 therapy.

SECONDARY OBJECTIVES:

I. To further elucidate efficacy endpoints of the combination the combination of BO-112 with pembrolizumab.

II. To demonstrate the efficacy of BO-112 from its hypothesized mechanism of action.

CORRELATIVE RESEARCH OBJECTIVES:

I. Peripheral blood will be collected to assess changes in circulating cluster of differentiation 4 (CD4+), cluster of differentiation 8 (CD8+), natural killer (NK), and dendritic cells.

II. Peripheral blood will be collected to assess leukocyte expression of interferon beta induced genes in conjunction with intratumoral studies to demonstrate increased intratumoral interferon beta and other hypothesized biomarkers.

III. A baseline biopsy will be collected on cycle 1 day 1 and at cycle 2 day 15 (done at the same time as intratumoral injection).

IIIa. From these biopsies, intratumoral CD4+, CD8+ expression and cluster of differentiation 56 (CD56+) expression (NK cells) will be measured by immunohistochemistry on the baseline biopsy and the biopsy on cycle 2 day 15.

IIIb. Myeloid dendritic cells will be assessed by flow cytometry, as their activity correlates with Toll-like receptor 3 (TLR3) activation.

IIIc. Percentage of cells with apoptosis and necrosis will be assessed. IIId. The tumor microenvironment will be assessed by ribonucleic acid (RNA) expression profiling with nCounter Pancancer Immune Profiling Panel given its extensive validation to date.

IV. To assess the potential of immune-related Response Evaluation Criteria in Solid Tumors (RECIST) (iRECIST) to determine disease control as compared to RECIST 1.1.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of odd number cycles. Patients also receive BO-112 by intratumoral injection on day 1, 8, and 15 of cycle 1, and day 15 of subsequent cycles. Treatment repeats every 3 weeks for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 1 year, and then every 12 weeks thereafter.

BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer

Pilot Feasibility Study of Intratumoral BO-112 in Combination With Pembrolizumab for Advanced Hepatocellular Carcinoma

ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR will be estimated and 95% Clopper-Pearson exact confidence intervals (CIs) will be provided.

Progression will be assessed per RECIST 1.1. PFS will be summarized using the Kaplan Meier method as well as descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum).

TTP will be summarized using the Kaplan Meier method as well as descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum).

DCR is defined as the proportion of subjects who have achieved CR, PR, or stable disease after \>= 5 weeks (the start of the window for the first scheduled scan) based on assessments by the site per RECIST 1.1.

OS will be summarized using the Kaplan Meier method as well as descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented. 12-month survival rate will be recorded.

Merck Sharp & Dohme LLC

Highlight Therapeutics

Jonsson Comprehensive Cancer Center

Blood and Lymph Conditions

Immune System Diseases

Behaviors and Mental Disorders

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Lymphoma

Melanoma

Neuroblastoma

Fibromatosis, Aggressive

Lymphoma, Non-Hodgkin

Colorectal Neoplasms

Endometrial Neoplasms

Aggression

Fibroma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Neoplasms, Fibrous Tissue

Pancreatic Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Lymphosarcoma

Desmoid Tumor

Tegavivint will be administered IV over 4 hours on days 1, 8, and 15 of each cycle. Administer D5W flush after completion of each tegavivint infusion. Treatment repeats every 28 days for up to 26 cycles or 24 months in the absence of disease progression or unacceptable toxicity. Drug doses should be adjusted based on the weight (height and BSA will also be captured) measured within 7 days prior to the beginning of each cycle. The starting dose will be 5 mg/kg with dose levels for subsequent cohorts increasing to 6.5 mg/kg and 8 mg/kg if excessive toxicity does not occur. If the MTD has been exceeded at the first dose level, then the subsequent cohort of patients will be treated at a dose of 4 mg/kg. Patients undergo an x-ray at baseline, after cycle 1, and then every 3 cycles while on treatment and DEXA scan at baseline and every 6 cycles while on treatment, then at 12 months, 24 months, and annually up to 60 months following end of therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors	NCT02867592	Adrenal Cortica... Alveolar Soft P... Central Nervous... Childhood Clear... Clear Cell Sarc... Ewing Sarcoma Hepatoblastoma Hepatocellular ... Osteosarcoma Recurrent Adren... Recurrent Alveo... Recurrent Clear... Recurrent Ewing... Recurrent Hepat... Recurrent Hepat... Recurrent Kidne... Recurrent Malig... Recurrent Osteo... Recurrent Prima... Recurrent Renal... Recurrent Rhabd... Recurrent Soft ... Recurrent Thyro... Refractory Adre... Refractory Alve... Refractory Clea... Refractory Ewin... Refractory Hepa... Refractory Hepa... Refractory Mali... Refractory Oste... Refractory Prim... Refractory Prim... Refractory Rena... Refractory Rhab... Refractory Soft... Refractory Thyr... Refractory Wilm... Renal Cell Carc... Rhabdomyosarcom... Soft Tissue Sar... Solid Neoplasm Thyroid Gland M... Wilms Tumor	Cabozantinib Cabozantinib S-... Pharmacological...	2 Years - 30 Years	National Cancer Institute (NCI)
BO-112 and Pembrolizumab for the Treatment of PD-1/PD-L1 Refractory Liver Cancer	NCT04777708	Advanced Hepato... BCLC Stage B He... BCLC Stage C He... Refractory Hepa...	Nanoplexed Poly... Pembrolizumab	18 Years -	Jonsson Comprehensive Cancer Center
Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors	NCT04851119	Colorectal Carc... Endometrial Car... Melanoma Neuroblastoma Ovarian Carcino... Pancreatic Duct... Recurrent Desmo... Recurrent Ewing... Recurrent Hepat... Recurrent Hepat... Recurrent Malig... Recurrent Non-H... Recurrent Osteo... Refractory Desm... Refractory Ewin... Refractory Hepa... Refractory Hepa... Refractory Mali... Refractory Non-... Refractory Oste... Solid Pseudopap... Wilms Tumor	Biospecimen Col... Dual X-ray Abso... Tegavivint X-Ray Imaging	12 Months - 30 Years	Children's Oncology Group

Spots Global Cancer Trial Database for refractory hepatocellular carcinoma