Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Nervous System Diseases

Rare Diseases

Melanoma

Glioblastoma

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Vaccines

Immunomodulating Agents

Immunologic Factors

* Assess Inflammation (PBR PET)
* Immunotherapy
* Assess Inflammation (PBR PET)

* Chemoradiation
* Assess inflammation (PBR PET)
* Follow Patients

PBR PET

Subjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms.

Cancer Immunotherapy

Subjects with glioblastoma will receive or will have received treatment with chemotherapy and radiation per the standard of care.

Radiation and chemotherapy

Elizabeth Gerstner, MD

This research study is studying the changes in primary and metastatic brain tumor inflammation using positron emission tomography (PET) imaging using a radioactive substance called \[11C\] PBR28a, which is also known as peripheral benzodiazepine receptors (PBR), or PBR-PET.

This research study is a Pilot Study, which is the first time investigators are examining this study intervention. The purpose of a pilot study is to obtain the preliminary data needed to justify performing a larger clinical trial on the effectiveness of an investigational intervention.

Standard treatment for the subjects' disease includes chemoradiation and immunotherapy.

In PET scans, a radioactive substance is injected into the body. The scanning machine finds the radioactive substance, which tends to go to cancer cells and areas of inflammation. For the PET scans in this study, the investigators are using a radioactive substance called \[11C\]PBR28.

The investigators would like to see if this tracer can be used to detect changes in inflammation during tumor treatment. PBR-PET scans will be performed at screening before therapy and then several weeks/months after the start of therapy, depending on the type of therapy used. No diagnostic decisions or clinical treatment decisions will be made based on any results obtained from these PET scans, and there will be no change in care. The information from these studies may help the investigators design methods that could be used in larger studies to more completely understand the role of inflammation in the treatment of cancer.

A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy

The change in PBR uptake in arms cohorts A and B from baseline to the start of cycle 4 for metastatic melanoma patients or cycle 3 for glioblastoma patients. The 18-kDa translocator protein (TSPO) is a protein that is expressed in mitochondria and is particularly prominently expressed by activated microglia, infiltrating macrophages, and reactive astrocytes. Thus, it is a marker of neuro-inflammation. PBR28 is a second generation PET tracer that binds to TPSO. PBR28 uptake was quantified using the standardized uptake value (SUV), which is the ratio of activity per unit volume of the region of interest (ROI) compared to cerebellum. Higher values indicate increased uptake in the ROI.

The median PBR28 uptake as measured by positron emission tomography (PET) following chemo-radiation. The 18-kDa translocator protein (TSPO) is a protein that is expressed in mitochondria and is particularly prominently expressed by activated microglia, infiltrating macrophages, and reactive astrocytes. Thus, it is a marker of neuro-inflammation. PBR28 is a second generation PET tracer that binds to TPSO. PBR28 uptake was quantified using the standardized uptake value (SUV), which is the ratio of activity per unit volume of the region of interest (ROI) compared to cerebellum. Higher values indicate increased uptake in the ROI.

Massachusetts General Hospital

Principal Investigators

Adverse event data were not collected as a part of this trial

* Assess Inflammation (PBR PET)
* Immunotherapy
* Assess Inflammation (PBR PET)

PBR PET

Cancer Immunotherapy: Subjects who are to be treated with immunotherapy for glioblastoma or melanoma brain metastases will be eligible for 2 of the 3 arms.

Metastatic Melanoma to the Brain (Cohort A)

Primary Brain Tumor (Cohort B)

* Chemoradiation
* Assess inflammation (PBR PET)
* Follow Patients

PBR PET

Radiation and chemotherapy: Subjects with glioblastoma will receive or will have received treatment with chemotherapy and radiation per the standard of care.

Primary Brain Tumor (Cohort C)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Elizabeth Gerstner

Before immunotherapy

During immunotherapy

Only a baseline measurement was taken for the 1 patient in cohort A. Change in PBR was therefore not possible to calculate for that patient. PBR PET was only assessed once in cohort C and is reported separately.

Change in PBR Uptake (Changes in PBR Uptake by PET)

Median PBR Uptake

Overall Study

Digestive System Diseases

Ear, Nose, and Throat Diseases

Mouth and Tooth Diseases

Deglutition Disorders

Head and Neck Neoplasms

Esophageal Diseases

Gastrointestinal Diseases

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Active Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES) therapy will be paired concomitantly with repeated effortful sallowing exercises, for 60 swallows, 2 times per day, 6 days per week, for 12 weeks.

Sham (inactive) Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES) therapy will be paired concomitantly with repeated effortful sallowing exercises, for 60 swallows, 2 times per day, 6 days per week, for 12 weeks.

NMES or Sham NMES will be paired with repeated, effortful swallowing behavior, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.

Neurotech NT2000 Neuromuscular Electrical Stimulation (NMES)

Susan Langmore, PhD,SLP,BRS

The purpose of the investigation is to learn whether intense swallowing exercise or intense swallowing exercise coupled with electrical stimulation (E-Stim) helps patients who had head/neck cancer and currently have dysphagia swallow better.

Head and neck cancer patients have a better chance of survival in the 21st century because of radiation therapy (RT), either alone or in combination with surgery and/or chemotherapy (CRT). Such therapy has a high rate of local / regional control, and may extend duration of life. Unfortunately the elimination of the cancer can leave devastating side effects, including the inability to eat and swallow normally. Organ preservation, often assumed to be the preferred treatment, has now been shown to magnify dysphagia. Incidence of dysphagia in this group of patients is extremely high, with symptoms continuing to deteriorate for several years after treatment. Conventional therapy for dysphagia yields only minor benefit. Persistence of dysphagia has a major impact on the quality of life of these cancer survivors.

Recently, a new therapy approach has been introduced for dysphagia, called e-stim or Neuromuscular Electrical Stimulation (NMES). Through low voltage current delivered through the skin, motor nerves are excited, causing muscle contraction. An aggressive marketing campaign has turned e-stim into a very popular and sought-after therapy for dysphagia. However, there are no efficacy studies demonstrating its true benefit.

We have collected preliminary data with Head \& Neck cancer patients using this modality and have seen improved swallow function in 9/15 patients. This is extremely promising and supports the need for a randomized clinical trial. The randomized controlled trial (RCT) proposed here will compare NMES therapy combined with exercise therapy to a sham NMES protocol combined with the same exercise therapy.

These therapies will be given to post-radiated H\&N cancer patients who have moderate to severe dysphagia at least 3 months post-XRT (or post-XRT + post-CRT), to determine whether NMES is efficacious. Therapy will continue for 12 weeks with an intense, daily home program. Objective indicators of a change in swallow function will be taken from modified barium swallow (MBS) studies. Subjective measures of change will be the patients' self-reported diet, eating ability, and quality of life, and will indicate whether they perceived a benefit from the therapy.

This new treatment may represent the first real hope for improved swallowing in this growing population of cancer survivors. We need to determine whether it represents a truly beneficial treatment or whether our resources should be redirected. If successful, this study will stimulate a multitude of additional research to elucidate the mechanisms underlying this new treatment.

Efficacy of Electrical Stimulation for Dysphagia in Head & Neck Cancer Patients

The PAS scale is a validated 8-point ordinal scale (Rosenbek et. al 1996) in which a score of 1 is best (material does not enter the airway) and a score of 8 is worst (material enters the airway, passes below the vocal folds, and no effort is made to eject it).

Difference in mean PAS scores after 12 weeks of therapy was analyzed between the two groups of interest: Active NMES + Swallowing Exercise versus Sham (inactive) NMES + Swallowing Exercise. PAS scores were obtained from fluoroscopy (modified barium swallow) studies adminstered at three time points - enrollment, midway through treatment (6 weeks), and at end of treatment (12 weeks). All fluoroscopy studies were sent to, and analyzed by, a blinded external central laboratory.

Perceive improved in quality of life and eating ability as measured by 2 validated scales: the Performance Status Scale for Head and Neck Cancer Patients (PSS) and The Head and Neck Cancer Inventory (HNCI).

The PSS (List, et. al., 1990) is a clinician adminsitered scale that has three domains (normalcy of diet, eating in public, and understandability of speech). Each domain as well as overall score is scored on a scale of 0-100, with 0=worst and 100=best.

The HNCI (Funk, et. al., 2003) is patient administered questionnaire that has four domains (social disruption, aesthetics, speech, eating). Each domain as well as overall score is scored on a scale of 0-100, with 0=worst and 100=best.

Northwestern University

Boston University

University of Wisconsin, Madison

New York University

VA Boston Healthcare System

Lahey Clinic

Lenox Hill Hospital

Beth Israel Medical Center

Greater Baltimore Medical Center

Henry Ford Hospital

University of California, San Diego

University of Washington

Mayo Clinic

Icahn School of Medicine at Mount Sinai

National Cancer Institute (NCI)

Boston Medical Center

Director, Speech Language Pathology

Active NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.

Active NMES + Swallowing Exercise

Sham (inactive) NMES paired concomitantly with repeated, effortful swallowing exercises, for 60 swallows, 2 times a day, 6 days a week, for 12 weeks.

Sham (Inactive) NMES + Swallowing Exercise

NMES therapy combined with exercise therapy

Active NMES Group

Sham NMES Group

Because of funding limitations research assistants could not be hired at most sites, and so 170 (instead of 240) subjects were enrolled. However, the results suggest additional patients would not have changed the outcome.

Dr. Susan Langmore, PhD, Director of Speech Language Pathology

Note: the number of participants analyzed (125) does not match the total number enrolled (170) because 45 people did not have adequate follow up data required for this primary analysis.

Change in Penetration-Aspiration Scale (PAS) Score

Change in Total PSS score

Change in HNCI Eating Domain

Note: the number of participants analyzed (126) does not match the total number enrolled (170) because 44 people did not have adequate follow up data required for this secondary analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy	NCT02431572	Intracranial Tu... Glioblastoma Melanoma	PBR PET Cancer Immunoth... Radiation and c...	18 Years -	Massachusetts General Hospital
Efficacy of Electrical Stimulation for Dysphagia in Head & Neck Cancer Patients	NCT00629265	Dysphagia	Neurotech NT200...	21 Years -	Boston Medical Center
A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy	NCT02431572	Intracranial Tu... Glioblastoma Melanoma	PBR PET Cancer Immunoth... Radiation and c...	18 Years -	Massachusetts General Hospital
A Pilot Study to Evaluate PBR PET in Brain Tumor Patients Treated With Chemoradiation or Immunotherapy	NCT02431572	Intracranial Tu... Glioblastoma Melanoma	PBR PET Cancer Immunoth... Radiation and c...	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for radiation and chemotherapy