Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Temozolomide

Valproic Acid

Histone Deacetylase Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Neurotransmitter Agents

Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

adjuvant therapy

Orally 75mg/m\^2 first day of radiation until completion. Restart 4 weeks post radiation.

External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Radiation therapy

Kevin A Camphausen, M.D.

Background:

* Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for treating brain tumors called glioblastomas.
* The drug valproic acid, currently approved for treating seizures, has been shown in laboratory tests to increase the radiosensitivity of glioma cells.

Objectives:

-To determine the effectiveness of adding valproic acid to standard treatment with radiation therapy and temozolomide for treating glioblastoma.

Eligibility:

-Patients 18 years of age and older with glioblastoma multiforme who have not been previously treated with chemotherapy of radiation.

Design:

* This Phase II trial will enroll 41 patients.
* Patients will receive radiation therapy to the brain once a day, Monday through Friday, for 6 1/2 weeks.
* Patients will take temozolomide once a day by mouth, Monday through Friday, during the period of radiation treatment. Starting 4 weeks after radiation therapy, patients will take temozolomide once a day for 5 days every 28 days for a total of six cycles.
* Patients will receive valproic acid by mouth twice a day beginning 1 week prior to the first day of radiation therapy and continuing until the completion of chemotherapy and radiation therapy.
* Patients will have follow-up visits 1 month after completing therapy, then every 3 months for 2 years, and then every 6 months for 3 years. Follow-up includes a physical examination, blood tests and magnetic resonance imaging of the brain.

BACKGROUND:

* Histone deacetylase inhibitors (HDACi) have recently been shown to enhance the radiosensitivity of glioma cells both in vitro and in vivo.
* Valproic acid has also recently been demonstrated to be a potent HDAC.
* Valproic acid has a long clinical history in patients with and without brain tumors and is known to cross the blood-brain barrier. However, the use of valproic acid in combination with temozolomide and radiotherapy for patients with high-grade gliomas has never been tested.

OBJECTIVES:

-The primary measure of efficacy will be progression free survival and overall survival.

ELIGIBILITY:

* Patients greater than 18 years old
* Diagnosis glioblastoma multiforme
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Patients who have not been previously treated with chemotherapy or radiation

DESIGN:

* This is a Phase II trial to determine the efficacy of valproic acid in combination with external beam radiation therapy and temozolomide in patients with high-grade gliomas.
* Patients will be treated with external beam radiation therapy in a standard manner with temozolomide given daily during the radiation. The valproic acid will be administered daily beginning one week prior to the first day of irradiation and continuing until the completion of chemoradiation.
* We anticipate that accrual to this trial of 41 patients will take approximately 1 year.

Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors

A Phase II Clinical Trial of the Histone Deacetylase Inhibitor Valproic Acid in Combination With Temodar and Radiation Therapy in Patients With High Grade Gliomas: Multi-Institutional Trial

Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.

Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a \>50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a \>25%, but \<50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).

Survival is the interval from the initiation of treatment on protocol to date of death.

Percentage of participants who were alive at 6, 12, and 24 months.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

adjuvant therapy

Temozolomide Orally 75mg/m\^2 first day of radiation until completion. Restart 4 weeks post radiation.

Valproic Acid Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

Radiation therapy External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Age, Continuous

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Kevin Camphausen, M.D.

Median Progression Free Survival.

Number of Participants With Adverse Events

6 months

12 months

24 months

Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

adjuvant therapy

Temozolomide: Orally 75mg/m\^2 first day of radiation until completion. Restart 4 weeks post radiation.

Valproic Acid: Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.

Radiation therapy: External beam radiation Monday-Friday in 2 Gy fractions to 60 Gy total.

Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months

Complete Response

Partial Response

Minor Response

Stable Disease

Progressive Disease

Not Evaluable

Number of Participants With Best Response

Median Overall Survival

Percentage of Participants With Overall Survival at 6, 12, and 24 Months

Overall Study

Astrocytoma

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Anti-Allergic Agents

Ondansetron

Dexamethasone

Curcumin

Dexamethasone acetate

Diphenhydramine

Promethazine

Prochlorperazine

Bismuth subsalicylate

Define the MTD/recommended Phase 2 dose (RP2D) of LC, administered IV weekly in combination with standard CRT (60 Gy in 30-33 fractions M-F, and daily oral TMZ 75 mg/m2), in patients with high grade malignant gliomas. This study seeks the MTD/RP2D of LC when added to TMZ during concurrent RT and adjuvant TMZ after RT. The study will evaluate escalating doses of LC delivered by IV infusion weekly as a gravity infusion (without infusion pump). Within each cohort, the dose will remain the same. In the first cohort, dosing will begin at Level 1 (300 mg/m2). The infusion of LC will begin at the start of CRT. Patients will be evaluable for the cohort if they have completed 80% of the planned doses of LC, 80% of RT and 60% of TMZ within the first 10 weeks of treatment. Patients who experience a dose-limiting toxicity (DLT) will be evaluable for the cohort if they have received at least 1 dose of LC.

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4mg IV, Diphenhydramine 25 mg IV - Dose: per treatment assignment Route: IV over 3 hours Schedule: Weekly: Weeks 1,2, 3,4,5,6 Cycle length: 6 weeks

Agent: TMZ Premedications/Precautions No food 2 hr before and after dosing Antiemetic (eg, ondansetron, prochlorperazine) 30 minutes before dosing Stool softener PRN. Dose: 75 mg/m2 Route: Oral Schedule: Daily during term of RT Cycle Length: 6 weeks

Agent: Radiotherapy Premedications/Precautions: n/a Dose: 2 Gy Route: External beam therapy Schedule: Monday-Friday Cycle Length 6 weeks

Concurrent CRT Period

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV Dose: Per treatment assignment Route: IV over 3 hours Schedule: Weekly: Weeks 7,8,9,10 Cycle length: 4 weeks

Post-CRT Period

Agent: LipoCurc Premedication/Precautions: Dexamethasone 4 mg IV Diphenhydramine 25 mg IV Dose: Per treatment assignment Route: IV over 3 hours Schedule: Weekly: Adjuvant Cycles 1-6: Weeks 1, 2, 3, 4 of each cycle Cycle Length: 4 weeks

Agent: TMZ Premedication/Precautions: No food 2 hr before and after dosing. Antiemetic (eg, ondansetron, prochlorperazine) 30 minutes before dosing Stool softener prn Dose: 150-200 mg/m2 (Cycles 1-6) Route: Oral Schedule: Daily Cycle Length: 4 weeks

Adjuvant Period

Vice President Regulatory Affairs and Operations

President, CEO

Matthias Holdhoff, MD, PhD

Stuart Grossman, MD, PhD

David Kamson, MD, PhD

Jaishri Blakeley, MD, PhD

Lawrence Kleinberg, MD, PhD

John Laterra, MD, PhD

Kristin Redmond, MD, PhD

Karisa Schreck, MD, PhD

Carlos Romo, MD, PhD

Peter Sordillo, MD, PhD

The objective of this study is to assess the tolerability, safety, and efficacy of Liposomal Curcumin (LC) in combination with radiotherapy (RT) and Temozolomide (TMZ) in patients with newly diagnosed High-Grade Gliomas (HGG).

This study is a Phase 1/2, single-center, single-institution, open-label, dose-escalation study in patients with newly diagnosed high-grade malignant gliomas. Dose finding will be performed using a time-to-event Bayesian optimal interval (TITE-BOIN) rule-based schema.

The primary objectives of the study are to determine the maximum tolerated dose /recommended phase 2 dose of Liposomal Curcumin (LC) in combination with radiotherapy (RT), and TMZ and adjuvant TMZ in newly diagnosed High-Grade Gliomas, and to determine the safety and tolerability of LC IV infused over 3-hours.

The secondary objectives are to estimate the safety and tolerability of LC in combination with standard RT and TMZ and adjuvant TMZ, to determine the feasibility of weekly LC infusion, defined as the number of patients being able to complete 80% of the planned doses of LC, 80% of RT, and 60% of TMZ within the first 10 weeks of treatment, and to assess efficacy as defined by overall survival (OS) and progression free survival (PFS) observed for each dose level.

This study is an unblinded, sequential treatment intervention employing 3 dose levels.

Approximately 50 patients will be screened to achieve up to 30 patients assigned to study intervention.

The duration of treatment for each patient will be up to 34 weeks. Treatment starts with the beginning of infusion and ends, if tolerated, at the end of Cycle 6 of adjuvant TMZ.

This study seeks the MTD/RP2D of LC when added to TMZ during concurrent RT and adjuvant TMZ after RT. The study will evaluate escalating doses of LC delivered by IV infusion weekly as a gravity infusion (without infusion pump). Within each cohort, the dose will remain the same. In the first cohort, dosing will begin at Level 1 (300 mg/m2). The infusion of LC will begin at the start of CRT. Patients will be evaluable for the cohort if they have completed 80% of the planned doses of LC, 80% of RT and 60% of TMZ within the first 10 weeks of treatment. Patients who experience a dose-limiting toxicity (DLT) will be evaluable for the cohort if they have received at least 1 dose of LC. There will be a maximum of 4 dose levels assessed in this study. The Safety Review Committee (SRC) will oversee dose level decisions throughout the dose escalation phase of the study.

Study of Liposomal Curcumin in Combination With RT and TMZ in Patients With Newly Diagnosed High-Grade Gliomas

Phase I/II Study of the Tolerability, Safety, and Efficacy of Liposomal Curcumin in Combination With Radiation and Temozolomide in Patients With Newly Diagnosed High-Grade Gliomas

The MTD/RP2D of LC in combination with RT and TMZ and adjuvant TMZ in newly diagnosed HGG will be determined by recording the number of observed dose limiting toxicities (DLTs). DLTs, as defined in this study occur if in the first three patients entered at a dose-level, more than one of these 3 experiences a serious adverse event, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5. If one of the first three patients entered at the level experiences an SAE (as defined by NCI CTCAE Version 5), then three additional patients are entered at that same dose level. If one of the additional three patients experiences an SAE (as defined by NCI CTCAE Version 5), the dose is not advanced beyond that level.

The safety and tolerability of LC infused IV over 3 hours will be assessed by recording the number of observed DLTs. DLTs, as defined in this study occur if in the first three patients entered at a dose-level, more than one of these 3 experiences a serious adverse event, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5. If one of the first three patients entered at the level experiences an SAE (as defined by NCI CTCAE Version 5), then three additional patients are entered at that same dose level. If one of the additional three patients experiences an SAE (as defined by NCI CTCAE Version 5), the dose is not advanced beyond that level.

The safety and tolerability of LC in combination with standard RT/TMZ and adjuvant TMZ will be assessed by recording the incidence of Adverse Events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Subjects will undergo medical history evaluations, physical and neurological examinations, brain MRI, functional assessment using the Karnofsky Performance Scale (KPS) Index, vital sign measurements, weight, adverse event assessments, concomitant medication assessments, and laboratory testing including but not limited to blood sample collection for hematology and chemistry, urinalysis, coagulation, lipid panel, electrocardiogram, and pregnancy test for females of childbearing potential.

The feasibility of weekly LC infusion will be assessed by recording the proportion of patients at each dose level who are able to complete at least 80% of the planned infusions of LC, 80% of RT, and 60% of TMZ during the first 10 weeks of treatment.

The efficacy of weekly LC infusion will be assessed by recording overall survival (OS) at each dose level, defined as the duration of time from the start of treatment with LC to time of death.

The efficacy of weekly LC infusion will be assessed by recording progression free survival (PFS) based on Response Assessment in Neuro-Oncology (RANO) criteria at each dose level, defined as defined as the duration of time from the start of treatment with LC to time of progression or death.

Avance Clinical Pty Ltd.

SignPath Pharma, Inc.

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Carcinoma

Lung Neoplasms

Sarcoma

Carcinoma, Renal Cell

Head and Neck Neoplasms

Adenocarcinoma

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

Soft Tissue Sarcoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Fluciclatide Injection (AH111585 (18F) Injection)

Fluciclatide Injection

Jeffrey Winick, Ph.D.

Study aimed to assess the reproducibility of PET imaging using AH111585 (18F) Injection. Subjects are evaluable if they undergo 2 administrations of AH111585 (18F) Injection (3 to 8 days apart) and the corresponding PET acquisitions, and tumors demonstrate detectable levels of 18F uptake on PET.

Reproducibility of 18F Uptake by Solid Tumors Using PET Imaging Following Intravenous Administration of (18F) Injection

A Test-retest Study to Assess Reproducibility of 18F Uptake by Solid Tumors Using PET Imaging Following Intravenous Administration of AH111585 (18F) Injection.

Mean relative differences of Standardized uptake value (SUV) following intravenous administration of AH111585 (F18) Injection between the two PET imaging sessions.

Safety was monitored throughout the duration of the subject's participation.

BIAFFIN GmbH & Co. KG (Biomolecular Interaction Analyses)

Quintiles, Inc.

i3 Statprobe

GE Healthcare

1 Fluciclatide Injection

India

Korea, Republic of

Sweden

United Kingdom

70 Subjects enrolled. A total of 49 subjects received a least one dose of Fluciclatide administration.

Matthew Miller

40 Minute Post Injection

65 Minute Post Injection

90 Minute Post Injection

Fluciclatide Injection (AH111585 (18F) Injection) at 10mCi \[370 megabecquerels (MBq)\]

Imaging Session 1

Imaging Session 2

The Relative difference between imaging sessions 1 and 2.

Relative Difference

Subjects received 2 doses of Fluciclatide Injection (AH111585 (18F) Injection).

Test Image and Retest Image Reproducibility of Fluciclatide Injection ([18F]AH111585) Uptake by Solid Tumors Following Intravenous Administration of AH111585 (18F) Injection Via PET Imaging.

Any TEAE

Total number of TEAEs

Any TEAE at least related to Drug

Intesity-Mild

Intensity-Moderate

Intensity-Severe

Any SAEs

Any SAE at least related to Drug

Any AE leading to Study Discontinuation

Any AE leading to Death

Any AE leading to death at least related to Drug

The number of adverse events in relationship to the categories descrbed using Fluciclatide Injection (AH111585 (18F) Injection).

Number of Adverse Events

The variable is looking at the Overall Summary of Treatment-Emergent Adverse Events (TEAE). Subjects could have experienced more than one TEAE. The category titles refer to Severe Adverse Events(SAE) and Adverse Events (AE).

The Safety of Greater Than or Equal to 2 Administrations, Each of a Maximum of 370MBq, Fluciclatide Injection (AH111585 (18F) Injection) in Subjects With Solid Primary or Metastatic Tumors.

AH111585 (18F) Injection : AH111585 (18F) Injection

Symptoms and General Pathology

Recurrence

Oligodendroglioma

Disease Attributes

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Patients will be treated with individualized starting dose of Niraparib.

The starting dose will be 300 mg niraparib (or modified according patient weight and platelet count), taken orally once a day for each cycle of 28 days.

James Battiste, MD

The purpose of this study is to determine what effects (good and bad) niraparib has on patients with recurrent brain cancer.

Patients will have tests and exams to see if they are eligible for the clinical trial. If found eligible, the patient will receive treatment with niraparib in the form of capsules taken every day for the first 28 days. If this dose is tolerated well, the patients will continue to take the capsules and more patients will be enrolled on the study.

Patients will continue treatment with niraparib while on the study unless there is evidence of tumor growth or they experience unacceptable side effects.

Patients will be monitored during treatment with tests and exams and after treatment completion for up to four years from the time they enrolled on the study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors	NCT00302159	High Grade Glio... Brain Tumors	adjuvant therap... Temozolomide Valproic Acid Radiation thera...	18 Years - 90 Years	National Institutes of Health Clinical Center (CC)
Study of Liposomal Curcumin in Combination With RT and TMZ in Patients With Newly Diagnosed High-Grade Gliomas	NCT05768919	Glioblastoma	Concurrent CRT ... Post-CRT Period Adjuvant Period	18 Years -	SignPath Pharma, Inc.
Reproducibility of 18F Uptake by Solid Tumors Using PET Imaging Following Intravenous Administration of (18F) Injection	NCT00918281	Solid Tumors High Grade Glio... Lung Cancer Head and Neck C... Sarcoma Renal Cell Carc... Breast Cancer	Fluciclatide In...	18 Years -	GE Healthcare
PARP Inhibition for Gliomas (PI-4G or π4g)	NCT05297864	Recurrent Gliob... Recurrent Astro... Recurrent Oligo... Recurrent Gliom...	Niraparib	18 Years -	University of Oklahoma
Chronic Convection Enhanced Delivery of Topotecan	NCT03154996	Gliomas	Topotecan Gadolinium Synchromed II i...	18 Years -	Columbia University
Studying the Biology of IDH-mutant Gliomas Via Longitudinal Observation of 2-hydroxyglutarate (2-HG) Using MR Spectroscopy	NCT03952598	Glioma Gliomas High Grade Glio... Malignant Gliom... Low Grade Gliom...	3T MRI scanner	18 Years -	National Institutes of Health Clinical Center (CC)
Valproic Acid With Temozolomide and Radiation Therapy to Treat Brain Tumors	NCT00302159	High Grade Glio... Brain Tumors	adjuvant therap... Temozolomide Valproic Acid Radiation thera...	18 Years - 90 Years	National Institutes of Health Clinical Center (CC)
Exploratory, Phase 0 Study of Positron Emission Tomography (PET) Imaging Agent, F-18 RGD-K5	NCT00743353	Sarcoma Melanoma Lung Cancer Breast Cancer High Grade Glio...	F-18 RGD-K5	18 Days -	Siemens Molecular Imaging
PARP Inhibition for Gliomas (PI-4G or π4g)	NCT05297864	Recurrent Gliob... Recurrent Astro... Recurrent Oligo... Recurrent Gliom...	Niraparib	18 Years -	University of Oklahoma
Compassionate Treatment in Children With Brain Tumors With the Cytotron®	NCT03577600	Pediatric Brain...	QMRT with the C...	3 Years - 16 Years	Hospital Infantil de Mexico Federico Gomez
Reproducibility of 18F Uptake by Solid Tumors Using PET Imaging Following Intravenous Administration of (18F) Injection	NCT00918281	Solid Tumors High Grade Glio... Lung Cancer Head and Neck C... Sarcoma Renal Cell Carc... Breast Cancer	Fluciclatide In...	18 Years -	GE Healthcare

Spots Global Cancer Trial Database for high grade gliomas