Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

1b dose exploration for 18 patients - The starting dose of ACT001 will be administered in combination with a single intravenous (IV) infusion of Pembrolizumab. After recovery from surgical resection, dosing will resume on a 3 weekly cycle and will consist of Pembrolizumab (standard dosing) and daily ACT001. Evaluation of a dose level of at least three (3) patients after completing one cycle of treatment post-surgery is required prior to commencing the next dose level.

30 Patients will be randomized to Arm A or Arm B at a ratio of 1 (Arm A) : 2 (Arm B). 10 patients will be randomized to the Pembrolizumab only arm (Arm A) and 20 patients will be randomized to the ACT001 plus Pembrolizumab arm (Arm B).

Phase1b - Starting approximately 2 weeks prior to the scheduled surgery, patient will receive an assigned dose of ACT001 by mouth in combination with a single dose of 200 mg pembrolizumab via an intravenous (IV-through a tube in vain) infusion in the clinic. Then patient will self administer ACT001 capsules twice daily by mouth, at the dose to which patient is assigned, until the evening prior to scheduled surgery. Patient will then undergo surgery to remove all or part of tumor. This a standard 3+3 dose escalation.

ACT001

Phase 2a - Starting approximately 2 weeks prior to the scheduled surgery, patient will receive a single dose of 200 mg pembrolizumab via an intravenous (IV) infusion in the clinic (an IV infusion means the drug will be delivered through a tube in your vein). Patient will then self-administer ACT001 capsules twice daily by mouth, at the dose to which patient is assigned, until the evening prior to scheduled surgery. Patient then will undergo surgery to remove all or part of tumor.

ACT001 + Pembrolizumab

C3 Research Associates

Shiao-Pei Weathers, MD

Vanessa Santiago, Sr Research Nurse

Doug Cai, MD

The current design provides a window to analyze the impact of the ACT001+Pembrolizumab combination on the tumor microenvironment and disease outcomes.

Phase 1b: The identified RP2D of combined ACT001 with Pembrolizumab will be determined by standard 3+3 dose escalation methodology among three ACT001 dosages (200mg, 400mg and 800mg, BID) with standard Pembrolizumab dosage. Patients will be dosed approximately 2 weeks prior to surgical resection with a single dose of Pembrolizumab and ACT001. Tumor resection will be performed and a biopsy will be obtained from the resected tumor tissue to evaluate the impact of the study drugs on the TME. After recovery from surgery, patients will resume ACT001 and Pembrolizumab until tumor progression (assessed by iRANO) or an AE requiring discontinuation of study drug. The Safety Monitoring Committee (SMC) will review the data available from all evaluable patients at each dose level prior to recommending escalation to the next dose level.

Phase 2a: Using the same dosing schedule and ACT001 dosage as determined in Phase 1b. Patients will be randomized to receive either Pembrolizumab only treatment (Arm A, 10 patients) or ACT001 plus Pembrolizumab treatment (Arm B, 20 patients).

Phase 1b dose exploration will enroll up to a maximum of 18 patients. Phase 2a, randomized/2-treatment arm part, will enroll up to 30 patients in two treatment arms. Arm A (treatment with Pembrolizumab) will enroll 10 patients. Arm B (treatment with the combination ACT001 plus Pembrolizumab) will enroll 20 patients.

A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme

A Phase 1b/2a Study of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme

A DLT is defined as any of the following

* Haematological toxicity

  * Grade 4 neutropenia
  * Grade ≥ 3 febrile neutropenia or neutropenic infection
  * Grade 4 thrombocytopenia
  * Grade 3 thrombocytopenia with clinically significant bleeding
* Non-haematological toxicity

  * Grade ≥ 3 nausea, vomiting or diarrhoea despite optimal supportive therapy
  * Grade ≥ 3 hypertension despite appropriate intervention
  * Other grade ≥ 3 non-haematological toxicity, except grade 3 fatigue or transient events (such as allergic reactions or electrolyte disturbances) that are readily controlled with medical therapy and/or are of no clinical concern

Mean change from baseline in vital sign measurements reported in beats/min (inclusive) at each study timepoint.

Mean change from baseline in vital sign measurements reported in mmHg at each study timepoint

Mean change from baseline in vital sign measurements reported in degrees Celsius (0C) at each study timepoint.

Mean change from baseline in vital sign measurements reported in bpm at each study timepoint

Mean change from baseline in electrocardiogram (ECG) parameters of heart rate, ventricular rate, PR interval, QRS duration, and QTcF.

Mean change from baseline in Karnofsky Performance Scale score

Determine ACT001 trough levels in tumor samples.

Overall survival (OS) is defined as time from start of ACT001 dosing at day 1 of cycle 1 until the date of death or date from any cause, assessed up to disease progression.

Summary of the treatment-emergent Adverse events experienced during treatment. Adverse events are assessed with Common Terminology Criteria for Adverse Events (CTCAE) 5.0. TEAEs are defined as any medical occurrence reported or observed after the start of dosing with investigational product until completion of the last study related procedure (including follow-up for safety assessments)

Avance Clinical Pty Ltd.

Accendatech USA Inc.

Sarcoma

Gliosarcoma

Soft Tissue Sarcoma

Temozolomide

in addition to standard radiation and chemotherapy, you will also receive the experimental hyperbaric treatment prior to each radiation treatment (Monday-Friday) during the initial six weeks of treatment. Prior to the first hyperbaric treatment. The hyperbaric treatment lasts approximately thirty minutes. During the hyperbaric treatment, the participant will lie on a stretcher in the hyperbaric chamber and breathe oxygen at greater than normal atmospheric pressure. The investigator will monitor the increased oxygen levels in the tissue by placing a noninvasive electrode on your skin. After each hyperbaric treatment, we will measure your blood sugar by finger-stick to check for hypoglycemia (low blood sugar). If detected, hypoglycemia will be treated by standard medical measures.

Hyperbaric Oxygen Therapy

Kerry E McConie, RN

Julia Trojanowski, RN

J Paul Duic, MD

Jai Grewal, MD

Standard treatment for glioblastomas includes radiation and chemotherapy with a drug called temozolomide (Temodar); however, glioblastomas frequently develop resistance to standard treatment and recur or progress. Glioblastomas are known to have decreased levels of oxygen compared to normal tissues. There is evidence that these lower oxygen levels in glioblastomas may contribute to their ability to resist treatment effects of radiation and chemotherapy. In this study we will look to increase the oxygen concentration within the glioblastoma by adding hyperbaric treatments (the experimental part of this study) to standard treatment with radiation and temozolomide in order to see whether increasing the oxygen concentration within the tumor increases the tumor-killing ability of standard radiation and chemotherapy.

In addition, the investigators are interested to evaluate the effect of this treatment protocol on a person's quality of life and level of stress, and, therefore, the investigators will ask subjects to complete several brief questionnaires while they are on-study.

All enrolled study subjects will receive treatment. Nobody will receive placebo. Before starting on-study, the investigators require standard blood tests (blood counts, chemistries, liver function tests, etc), urinalysis, serum pregnancy test (females of childbearing potential only) and an MRI with contrast (or CAT scan if you are unable to obtain MRI) that the investigators routinely obtain before starting any new treatment or chemotherapy.

Standard treatment for newly diagnosed glioblastomas after surgery begins with six weeks of combined radiation (Monday-Friday) and chemotherapy with an oral drug called temozolomide (Temodar) that patients normally take at home daily (including weekends) during the six weeks. Patients then have four weeks off treatment. After four weeks off, patients resume taking temozolomide on a monthly basis. During this phase of treatment, patients take a higher dose of temozolomide for only five days out of every twenty eight days (they take the drug only during the first five days of every 28 day cycle with the remaining 23 days off drug). Patients continue taking temozolomide on a monthly basis until tumor progression, they complete six to twelve months of treatment or they are unable to tolerate the drug any longer due to side effects.

Temozolomide is typically taken once daily on an empty stomach one-half hour after taking an anti-nausea medication that is also prescribed by your physician. Patients taking temozolomide are also instructed to take lactulose as needed for constipation.

During the initial six weeks of combined radiation and chemotherapy, patients also take an antibiotic to protect against a specific type of pneumonia that commonly occurs in people with weakened immune systems (pneumocystis carinii). Following completion of the combined phase of radiation and chemotherapy, continuation of the antibiotic depends upon the discretion of the treating physician.

In this study, in addition to standard radiation and chemotherapy described above, the patient will also receive the experimental hyperbaric treatment prior to each radiation treatment (Monday-Friday) during the initial six weeks of treatment. Prior to the first hyperbaric treatment, the patient will need to have a chest x-ray performed to make certain that you do not have any preexisting abnormal air spaces in the chest or lungs that could be worsened by hyperbaric treatment. The hyperbaric treatment lasts approximately thirty minutes. During the hyperbaric treatment, the patient will lie on a stretcher in the hyperbaric chamber and breathe oxygen at greater than normal atmospheric pressure. The investigators will monitor the increased oxygen levels in the tissue by placing a noninvasive electrode on your skin. After each hyperbaric treatment, the investigators will measure the participants blood sugar by finger-stick to check for hypoglycemia (low blood sugar). If detected, hypoglycemia will be treated by standard medical measures.

Blood tests will be obtained as per routine standard of care (weekly during the initial six weeks of combined radiation and chemotherapy) and on days # 21 and 28 (+/- 2 days) of each cycle of monthly temozolomide.After the initial MRI (or CAT scan), subsequent MRI's (or CAT scans) will be obtained per standard of care: four weeks after completion of radiation and then generally after every two cycles of chemotherapy unless medically indicated at other time points.

Other scans such as PET scans may be obtained if medically indicated as per standard of care.

This study also looks to evaluate the effect of this treatment regimen on the quality of life for the patient and level of stress. Therefore, the investigators will ask the patient to complete three brief questionnaires at several different time points: before starting the study, at the follow-up visit three to four weeks after completion of radiation, after completion of every two cycles of monthly temozolomide and after coming off study (if possible.) The patient will remain on study until completion of one year of treatment, the patient may voluntarily elect to withdraw from study, the patient cannot tolerate further treatment or side effects prevent continuing on study or there is evidence of tumor progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme	NCT05053880	Recurrent Gliob...	ACT001 ACT001 + Pembro...	18 Years -	Accendatech USA Inc.
A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme	NCT05053880	Recurrent Gliob...	ACT001 ACT001 + Pembro...	18 Years -	Accendatech USA Inc.
A Study to Evaluate Safety and Efficacy of ACT001 and Anti-PD-1 in Patients With Surgically Accessible Recurrent Glioblastoma Multiforme	NCT05053880	Recurrent Gliob...	ACT001 ACT001 + Pembro...	18 Years -	Accendatech USA Inc.
Hyperbaric Hyperoxygenation With Radiotherapy and Temozolomide in Adults With Newly Diagnosed Glioblastoma	NCT00936052	Glioblastomas Gliosarcoma	Hyperbaric Oxyg...	18 Years -	Neurological Surgery, P.C.

Spots Global Cancer Trial Database for blastoma

Every month we try and update this database with for blastoma cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for blastoma

Every month we try and update this database with for blastoma cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for blastoma cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.