Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Lung Neoplasms

Pancreatic Neoplasms

Melanoma

Glioblastoma

Brain Neoplasms

Central Nervous System Neoplasms

Neurofibromatoses

Neurofibromatosis 1

Pancreatic Cancer

Neurofibromatosis

Neurofibromatosis Type 1

Herbal and Botanical

All Drugs and Chemicals

Cola

A classic "3+3" design will be used to explore the maximum tolerated dose (MTD) and to determine the recommended phase II dose (RP2D). Three to four patients will be enrolled to ensure at least 3 evaluable patients for DLT (Dose Limiting Toxicity). ABM-168 monotherapy will be conducted in seven provisional dose levels starting at 0.5mg oral administration per day and up to and including 12mg oral administration. Each treatment cycle is 28-days. DLT will be evaluated in the first 28-day cycle. Patients will receive daily doses of ABM-168 until disease progression; intolerable toxicity; withdrawal consent; or other clinical observation is met.

Expansion will be conducted in the adult patients with advanced solid tumors that carry either RAS, RAF or NF-1 mutations. Cohort EX1 will enroll the patients with preferred indications (i.e., melanoma, colon cancer, lung cancer, and pancreatic carcinoma) who had confirmed RAS, RAF or NF-1 mutations and measurable target lesion(s) at baseline. Patients with measurable brain metastases lesion(s) at baseline are highly preferred. Up to 15 evaluable patients will be enrolled for each into each preferred indication. Other indication(s) that show confirmed response, complete response (CR) or partial response (PR) in at least one subject in the dose escalation study will facilitate the preferred indication(s) for Cohort EX1 enrollment as well.

Expansion will be conducted in the adult patients with advanced solid tumors that carry either RAS, RAF or NF-1 mutations. Cohort EX2 will enroll the patients who had primary CNS tumors with confirmed RAS, RAF or NF-1 mutations at baseline. Up to 30 evaluable patients will be enrolled.

Dosage: 0.5 mg; 2 mg; 6 mg; once daily by oral administration

ABM-168

Katie Zhou

Michael Wong

Katy Tsai, M.D.

Mateusz Opyrchal, M.D.

Suzanne Bailey

Taryn Bollaro

Sanjay Goel, MD

Rabia Khan

Sarina A. Piha-Paul, M.D.

Shiraj Sen, MD, PhD

Ignacio Garrido-Laguna, M.D.

Jamie White

This is a Phase 1, First-in-Human (FIH), open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ABM-168 in adult patients with RAS or RAF or NF-1 mutated advanced solid tumors as ABM-168 may have a significant effect in inhibiting cell growth.

This is a First-in-Human (FIH), open-label, multicenter, dose escalation and dose expansion, Phase I study of ABM-168, for the treatment of advanced solid tumors in adult patients.

The study consists of two parts:

Part A: Dose escalation. The starting dose of ABM-168 is 0.5 mq po qd, and dose escalation will be guided by a "3+3" design. ABM-168 will be administered once daily on a continuous schedule. Each treatment cycle consists of 28 days.

Part B: Dose Expansion. Expansion will be conducted in the adult patients with advanced solid tumors that carry either RAS, RAF or NF-1 mutations. There are two cohorts for Dose Expansion: Patients will be enrolled into either Dose Expansion Cohort 1 (EX1) or Dose Expansion Cohort 2 (EX2).

* Cohort EX1: Patients enrolled will have preferred indications (i.e., melanoma, colon cancer, lung cancer, and pancreatic carcinoma) who had confirmed RAS, RAF or NF-1 mutations and measurable lesion(s) at the beginning of the study. Patients with measurable brain lesions(s) which have metastasized are highly preferred.
* Cohort EX2: Patients enrolled will have primary CNS (Central Nervous System tumors with confirmed RAS, RAF or NF-1 mutations.

Dose limiting toxicity (DLT) will be evaluated and managed per the pre-defined DLT criteria and rules specified in the protocol. MTD (Maximum Tolerated Dose) and/or RP2D will be determined based on the totality of safety, clinical pharmacokinetics, and efficacy data from all evaluable patients enrolled and in treated in both dose escalation cohorts and dose expansion cohorts. The RP2D (recommended phase II dose) could be the MTD, or alternatively a dose recommended by the SMC (Safety Monitoring Committee) if no MTD is determined in the dose escalation and/or dose expansion.

Study consists of two parts:

* Part A: ABM-168 Dose Escalation and DLT Dose Confirmation
* Part B: Dose Expansion (ABM-168 Monotherapy)

Safety and Effectiveness of ABM-168 in Adults With Advanced Solid Tumors.

A Phase I, First-In-Human, Multicenter, Open Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety and Efficacy of ABM-168 Administered Orally in Adult Patients With Advanced Solid Tumors

Dose limiting toxicities (DLT) which defines the MTD/RP2D

Safety and tolerability of ABM-168 monotherapy as determined by incident rate.

Safety and tolerability of ABM-168 monotherapy as determined by severity. Adverse events will be assessed according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. For consistency, Version 5.0 will be used throughout the trial regardless of any subsequent versions of the CTCAE criteria that may become available. If CTCAE grading does not exist for a specific adverse event, the severity should be assessed based on the general guidelines outlined in CTCAE v5.0.

Safety and tolerability of ABM-168 monotherapy as determined by causality of adverse events (AEs).

Safety and tolerability of ABM-168 monotherapy as determined by clinically significant abnormalities in clinical laboratory testing.

Safety and tolerability of ABM-168 monotherapy as determined by body temperature changes from base-line in Fahrenheit.

Safety and tolerability of ABM-168 monotherapy as determined by heart rate changes from base-line in BPM (beats per minute).

Safety and tolerability of ABM-168 monotherapy as determined by pulse rate changes from base-line in BPM (beats per minute).

Safety and tolerability of ABM-168 monotherapy as determined by respiratory rate changes from base-line in breaths per minute.

Safety and tolerability of ABM-168 monotherapy as determined by blood pressure changes from base-line in systolic blood pressure (measured in mmHg).

Safety and tolerability of ABM-168 monotherapy as determined by blood pressure changes from base-line in diastolic blood pressure (measured in mmHg).

Safety and tolerability of ABM-168 monotherapy as determined by ophthalmology assessment.

Safety and tolerability of ABM-168 monotherapy as determined by ECGs (QT interval).

Safety and tolerability of ABM-168 monotherapy as determined by ECOG scores (0-Fully active; - 5-Dead).

Safety and tolerability of ABM-168 monotherapy as determined by Karnofsky performance scores - 70 (able to care for self and live at home) - 100 (able to carry on normal activity).

ABM Therapeutics Corporation

Symptoms and General Pathology

Behaviors and Mental Disorders

Necrosis

Disease Progression

Disease Attributes

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Quality of Life

Patients with radiographic evidence of lesion regrowth following prior treatment with stereotactic radiosurgery (regardless of the process being suspected recurrent or progressive brain metastasis versus radiation necrosis) and who already scheduled for NeuroBlate procedure.

Veronica Chiang, MD

The need for new technologies and devices in the field of neurosurgery is well established. In April 2013, FDA cleared NeuroBlate™ System, minimally invasive robotic laser thermotherapy tool. It employs a pulsed surgical laser to deliver targeted energy to abnormal brain tissue caused by tumors and lesions. This post-marketing, multi-center study will include patients with metastatic tumors who failed stereotactic radiosurgery and are already scheduled for NeuroBlate procedure. The study will collect clinical outcome, Quality of Life (QoL) and, where feasible, healthcare utilization data for publication.

Laser Ablation After Stereotactic Radiosurgery

To describe local (CNS) progression-free survival rate in patients with failed radiosurgery for brain metastases treated with the NeuroBlate System. Sites were requested to submit imaging to a centralized core laboratory for analysis. A total of 27 patients had images submitted--27/42 (64%) of patients submitted follow-up images at 12-weeks and 16/42 (38%) patients submitted follow-up imaging at 26 weeks. Due to the low submission of follow-up images at 26-weeks, 12-weeks and last follow-up are reported.

FACT-Br questionnaire sub-scores (Physical well-being, social/family well-being, emotional well-being, functional well-being, brain cancer subscale) are summed together, leading to a FACT-Br total score on a scale from 0-200; larger scores indicate better overall quality of life. This outcome measured the FACT-Br score change from Baseline at both 12 and 26 weeks post NeuroBlate procedure (values at 12 and 26 weeks, respectively, minus value at baseline). Version 4 of the Fact-BR scoring guidelines were used.

To describe/estimate the overall survival after the NeuroBlate Procedure.

To continue to monitor factors impacting the safe and efficacious use of NeuroBlate

Monteris Medical

Events adjudicated as surgery- or LITT- associated are described in the adverse events section.

Main Cohort

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Biopsy-confirmed radiation necrosis or metastatic brain tumor

Limitations are discussed by the physicians in the full publication of the LAASR study data (open access): http://thejns.org/doi/pdf/10.3171/2017.11.JNS171273

Nissa Mollema (Clinical Operations Manager)

12-weeks

Last Follow-up

NeuroBlate Procedure

Sites were requested to submit imaging to a centralized core laboratory for analysis. A total of 27 patients had images submitted--27/42 (64%) of patients submitted follow-up images at 12-weeks and 16/42 (38%) patients submitted follow-up imaging at 26 weeks.

Percentage of Patients With Progression-Free Survival (PFS)

Change in 12-week FACT-Br from Baseline

Change in 26-week FACT-Br from Baseline

Due to study attrition, the full cohort was unavailable for analysis.

Quality of Life (Change in The Functional Assessment of Cancer Therapy-Brain (FACT-Br) Score.

12-week Kaplan-Meier survival

26-week Kaplan-Meier survival

Overall Survival

Percentage of Patients With Laser Ablation Related Adverse Events

Patients with radiographic evidence of lesion regrowth following prior treatment with stereotactic radiosurgery (regardless of the process being suspected recurrent or progressive brain metastasis versus radiation necrosis) and who underwent the NeuroBlate procedure

Overall Study

Edema

Brain Edema

Adrenocorticotropic Hormone

Corticotropin-Releasing Hormone

Xerecept

This is a phase II, multicenter, open-label, imaging study of hCRF in the reduction of PBE in patients with primary malignant or metastatic brain tumors. Approximately 30 to 60 patients will be assigned to 1 of 3 treatment groups and receive study drug for up to 28 days

The purpose of this study is to investigate the effect of 3 different regimens of subcutaneous (SC) administered hCRF (1.0 mg every \[Q\] 8 hours \[h\], 1.5 mg Q12h, and 1.0 mg Q12h) on the reduction of PBE in patients with primary malignant or metastatic brain tumors as defined by MRI indexes.

Imaging Study of XERECEPT® Treatment for Peritumoral Brain Edema (PBE)

Open-Label, Imaging Study of Human Corticotropin-Releasing Factor (hCRF) for The Reduction of Peritumoral Brain Edema (PBE) in Patients With Primary Malignant or Metastatic Brain Tumors

Celtic Pharma Development Services

PharmaNet

Pharmanet

Blood and Lymph Conditions

Immune System Diseases

Musculoskeletal Diseases

Eye Diseases

Lymphoma

Pituitary Diseases

Recurrence

Glioma

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Meningioma

Germinoma

Astrocytoma

Pituitary Neoplasms

Ependymoma

Craniopharyngioma

Adamantinoma

Oligodendroglioma

Chordoma

Neoplasms, Neuroepithelial

Optic Nerve Glioma

Glioma, Subependymal

Lymphosarcoma

Germ Cells Tumors

Central Nervous System Germinoma

Brain Tumor, Childhood

Primary Central Nervous System Lymphoma

Anaplastic Astrocytoma

Pilocytic Astrocytoma

Subependymoma

Antineoplastic Agents

Dermatologic Agents

Central Nervous System Depressants

Dihematoporphyrin Ether

Trioxsalen

Hematoporphyrin Derivative

Ether

Photosensitizing Agents

Photofrin (porfimer sodium) photodynamic therapy.

Intravenous (IV) Photofrin

This is a dose escalation study. Patients will receive Photofrin via an IV infusion approximately 24 hours prior to their tumor resection surgery and Photodynamic Therapy (PDT). Patients will be light sensitive immediately upon receiving the Photofrin and must observe photosensitivity \& light precautions for a minimum of 30 days after the infusion.

Photodynamic Therapy (PDT)

After tumor resection, an optical fiber will be placed in the approximate center of the surgical cavity. Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniform delivery. Photoactivation of Photofrin is controlled by the total light dose delivered over the treatment time.

Photofrin (porfimer sodium) & photodynamic therapy.

Harry T Whelan, MD

Jeff Knipstein, MD

The goal of this proposal is to evaluate a new Photodynamic Therapy (PDT) modification which could revolutionize the treatment of brain tumors in children and adults. There are currently few cases published involving the use of PDT in infratentorial (in the posterior fossa) brain tumors in general and specifically those occurring in children. The investigators propose to test a technique, for the first time in the U.S., that demonstrated in Australian adult glioblastoma patients dramatic long-term, survival rates of 57% (anaplastic astrocytoma) and 37% (glioblastoma multiforme). These results are unprecedented in any other treatment protocol.

Photodynamic therapy (PDT) is a paradigm shift in the treatment of tumors from the traditional resection and systemic chemotherapy methods. The principle behind photodynamic therapy is light-mediated activation of a photosensitizer that is selectively accumulated in the target tissue, causing tumor cell destruction through singlet oxygen production. Therefore, the photosensitizer is considered to be the first critical element in PDT procedures, and the activation procedure is the second step. The methodology used in this proposal utilizes more intensive laser light and larger Photofrin photosensitizer doses than prior PDT protocols in the U.S. for brain tumor patients. The PDT will consist of photoillumination at 630 nm beginning at the center of the tumor resection cavity, and delivering a total energy of 240 J cm-2. The investigators feel that the light should penetrate far enough into the tissue to reach migrating tumor cells, and destroy these cells without harming the healthy cells in which they are dispersed.

The investigators will be testing the hypothesis that pediatric subjects with progressive/recurrent malignant brain tumors undergoing PDT with increased doses of Photofrin® and light energy than were used in our previous clinical study will show better progression free survival (PFS) and overall survival (OS) outcomes. PDT will also be effective against infratentorial tumors. The specific aims include determining the maximum tolerable dose (MTD) of Photofrin in children and looking for preliminary effectiveness trends.

Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors

Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study

MTD is defined as the Photofrin® dose that precedes the dose level used with a subgroup of subjects that exhibits a greater than 33% DLT occurrence.

DLT is defined as any of the following events with reasonable possibility to be attributable to the experimental intervention:

1. Neurotoxicity: defined as a decline in neurological function manifest within 1 week of PDT and persistent to 4 weeks post-PDT. Adverse events of neurologic function of grade 4, or a level change from grade 1 to grade 3, within this period will constitute neurotoxicity for this study. The CTCAE V4.02 will be used.
2. Photosensitivity: defined as a photosensitivity adverse event (CTCAE category dermatology/skin) of grade 4 occurring within the same period.
3. Ocular sensitivity: Photofrin®-induced ocular sensitivity is defined as a photophobia adverse event (CTCAE category ocular/visual) of grade 4 within the same period.
4. Any other toxicity of CTCAE grade 4 or higher within the same period.

To preliminarily define the antitumor activity of Photofrin and laser light activation within the confines of a Phase 1 Study. We will follow progression free survival and overall survival for 3 years post PDT treatment.

Pinnacle Biologics Inc.

Bleser Professor of Neurology

Breast Neoplasms

Triple Negative Breast Neoplasms

Neoplasm Metastasis

Neoplasms, Second Primary

Breast Diseases

Skin Diseases

Neoplastic Processes

Paclitaxel

Albumin-Bound Paclitaxel

Trastuzumab

Participants received ANG1005 intravenously (IV) at a dose of 600 mg/m\^2 on Day 1 of each 21-day cycle. ANG1005 will be administered for up to a maximum of one year, or until disease progression or adverse events (AE) that are not tolerated.

ANG1005

Betty Lawrence

This is a Phase 2 study to see if an investigational drug, ANG1005, can shrink tumor cells in breast cancer patients with recurrent brain metastases.

ANG1005 in Breast Cancer Patients With Recurrent Brain Metastases

A Phase II, Open-Label, Multi-Center Study of ANG1005 in Breast Cancer Patients With Recurrent Brain Metastases

To determine the drug concentration and distribution in the plasma. (AUC, Cmax, T1/2)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Effectiveness of ABM-168 in Adults With Advanced Solid Tumors.	NCT05831995	Advanced Solid ... RAS Mutation RAF Mutation NF1 Mutation	ABM-168	18 Years -	ABM Therapeutics Corporation
Laser Ablation After Stereotactic Radiosurgery	NCT01651078	Metastatic Brai... Progression Radiation Necro... Quality of Life		18 Years -	Monteris Medical
Imaging Study of XERECEPT® Treatment for Peritumoral Brain Edema (PBE)	NCT00691522	Peritumoral Bra... PRIMARY MALIGNA...	Xerecept	18 Years - 65 Years	PharmaNet
Safety and Effectiveness of ABM-168 in Adults With Advanced Solid Tumors.	NCT05831995	Advanced Solid ... RAS Mutation RAF Mutation NF1 Mutation	ABM-168	18 Years -	ABM Therapeutics Corporation
Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors	NCT01682746	Brain Tumor, Re...	Photofrin (porf...	6 Months - 18 Years	Medical College of Wisconsin
Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors	NCT01682746	Brain Tumor, Re...	Photofrin (porf...	6 Months - 18 Years	Medical College of Wisconsin
ANG1005 in Breast Cancer Patients With Recurrent Brain Metastases	NCT02048059	Breast Cancer Brain Metastase...	ANG1005	18 Years -	Angiochem Inc
Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors	NCT01682746	Brain Tumor, Re...	Photofrin (porf...	6 Months - 18 Years	Medical College of Wisconsin
Imaging Study of XERECEPT® Treatment for Peritumoral Brain Edema (PBE)	NCT00691522	Peritumoral Bra... PRIMARY MALIGNA...	Xerecept	18 Years - 65 Years	PharmaNet

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