Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Hypofractionated external beam radiation delivered in 4 different sequential dose/fractionation groups.

Study group 1: 3.5 Gray x 10, 5 fractions per week. Study group 2: 3.5 Gray x 10 + 7 Gray boost to biological target volume, 5 fractions per week. Study group 3: 5.9 Gray x 10, 5 fractions per week. Study group 4 (planning target volumes: 100 millilitres - 300 millilitres): 3.5 Gray x 10, 5 fractions per week. Phase II dosis: to be chosen based on results of phase I study.

External beam radiotherapy

Svend Aage Engelholm, MD

The purpose of the study is to evaluate the short- and long term toxicity of radiotherapy to patients with recurrent high-grade glioma who have previously received radiotherapy and to determine the best dose and treatment regimen. Positron emission tomography (PET) using an amino acid tracer, 18-fluoro-ethyltyrosine (18F-FET), is used for target delineation.The study examines, in four sequential treatment groups, the effect of dose, hypofractionation and treatment volume on toxicity. Upon completion of the phase I part, the study progresses to phase II where the best dose- and treatment regimen will be chosen for treatment.

Image Guided Reirradiation of High-grade Glioma

Image Guided Reirradiation of High-grade Glioma - a Phase I/II Dose Escalation Study

Early (\<4 weeks) and late (\> 4 weeks) toxicity evaluated by Common Toxicity Criteria ver. 3.0 at multiple time points up to one year after treatment. (for phase I part of the study)

Diagnostic accuracy (positive- and negative predictive value) of 18F-FET-PET guided biopsies (optional procedure) in patients who will receive reirradiation for recurrent high-grade glioma in the study. (for phase I part of the study).

Time to neurocognitive decline assessed using a test battery comprised of validated tests at multiple time points. (for phase II part of the study)

Time to disease progression evaluated by RANO (Response Assessment in Neuro-Oncology) criteria (for phase II part of the study).

Prognostic value of 18F-FET-PET scan at baseline, value of 18F-FET-PET as an early response marker and correlations between 18F-FET-PET scans and magnetic resonance imaging.

Rate of objective tumor responses following treatment evaluated by RANO criteria and by 18F-FET-PET.

Danish Center for Interventional Research in Radiation Oncology (CIRRO)

Rigshospitalet, Denmark

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Mouth and Tooth Diseases

Musculoskeletal Diseases

Head and Neck Neoplasms

Laryngeal Diseases

Paranasal Sinus Neoplasms

Laryngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Nose Neoplasms

Nose Diseases

Paranasal Sinus Diseases

Laryngeal Cancer

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Antineoplastic Agents

Amino Acids

Mitogens

Celecoxib

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Tyrosine

In this phase I/II study, patients will be treated with daily erlotinib 150 mg and twice-daily celecoxib 200 to 600 mg for 14 days. Re-irradiation with IMRT will start on day 15 and will continue for 5.5 to 6.5 weeks along with erlotinib and celecoxib. After completion of radiation, patients will be given the option of continuing on erlotinib for 2 years or until unacceptable toxicity or disease progression

erlotinib + celecoxib

Johnny Kao, M.D.

There is no optimal treatment for patients with recurrent head and neck cancer after previous radiation. Chemotherapy alone is not curative and patients survive an average of only 6 to 10 months. Surgery is not always possible and often cannot remove every cancerous cell. On the other hand, reirradiation with chemotherapy cures approximately 25 to 30% of patients but has significant toxicity with as many as 15 to 20% suffering from life-threatening or fatal complications. Therefore, less toxic and more effective reirradiation regimens are urgently needed. There are extensive data from animal studies and preliminary human studies showing that blocking epidermal growth factor receptor (EGFR) and COX-2 enhances radiation effect and is more effective than either treatment alone. Erlotinib is a FDA approved oral inhibitor of EGFR and celecoxib is a FDA approved COX-2 inhibitor. Both have been well studied in humans and appear to have less severe toxicity than conventional chemotherapeutic agents.

Despite advances in the treatment of head and neck cancer, locoregional recurrences are the predominant site of treatment failure and are frequently the cause of death. Second primary tumors in the head and neck occur in up to 30% of patients at 10 years of follow-up after eradication of the original tumor due to field cancerization. The standard approach to patients with recurrent but non-metastatic disease has been surgical salvage alone. Unfortunately, this strategy is feasible in only a select group of patients and 5 year survival rates have ranged from 15-40%.

Most patients with previously irradiated unresectable recurrent or metastatic head and neck cancer are treated with chemotherapy alone. This approach has offered limited palliation with response rates of 10-40%, median survival of 5 to 10 months. While this may be an acceptable option for patients with clearly incurable widespread metastatic disease, it may not be the best approach for those patients with potentially curable locoregional disease.

While geographic misses and second primary tumors occur, the majority of patients have radioresistant tumors. Therefore, reirradiation alone is unlikely to be effective. High dose reirradiation with concomitant chemotherapy represents a more aggressive approach resulted in encouraging 3-year survival rates of 15 to 35%. This approach represents a potentially curative option for patients with unresectable or partially resected disease arising in a previously irradiated volume. However, the high rates of acute and late toxicity with this approach have limited widespread application of this approach.

Extensive preclinical and clinical data suggest that both epidermal growth factor receptor (EGFR) antagonists and cyclooxygenase-2 (COX-2) inhibitors enhance the effectiveness of ionizing radiation. In locally advanced head and neck cancer, a recent phase III trial concurrent anti-EGFR monoclonal antibody and radiation demonstrated improved local control, disease free survival and overall survival compared to radiation alone without the increased mucosal toxicity associated with concurrent chemotherapy. COX-2 inhibition and anti-EGFR therapy demonstrates activity against recurrent/metastatic head and neck cancer in a recent phase I study. Head and neck cancer represents an ideal site to study biologic markers of tumor response because of the accessibility of tumors for biopsy. Therefore, we propose the combination of Erlotinib and Celecoxib with radiation in a cohort of previously irradiation patients with head and neck cancer.

Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer

Phase I/II Dose Escalation Trial of Induction and Concomitant Erlotinib and Celecoxib With Radiation Therapy for Treatment of Poor Prognosis Head and Neck Cancer, Including Reirradiation

Number of participants with acute and late toxicity

Response to Concurrent Erlotinib, Celecoxib, and Reirradiation according to Response Evaluation Criteria in Solid Tumors - Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Patients with locoregional and/or distant progression

At a median follow-up of 11 months, the 1 year locoregional control, progression-free survival, and overall survival rates.

Johnny Kao

Assistant Professor

erlotinib + celecoxib: In this phase I/II study, patients will be treated with daily erlotinib 150 mg and twice-daily celecoxib 200 to 600 mg for 14 days. Re-irradiation with IMRT will start on day 15 and will continue for 5.5 to 6.5 weeks along with erlotinib and celecoxib. After completion of radiation, patients will be given the option of continuing on erlotinib for 2 years or until unacceptable toxicity or disease progression

Erlotinib + Celecoxib

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

The Eastern Cooperative Oncology Group (ECOG) 0 - Fully active, able to carry on all pre-disease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature 2- Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours

ECOG Performance Status

None to minimal

20-40

Unknown

Tobacco use, pack-years

Primary recurrence

Second or later recurrence

Second primary cancer

Recurrent vs secondary primary

Squamous cell carcinoma

Adenoid cystic

Histology

Sinonasal

Ear/facial skin

Oropharynx

Oral cavity

Hypopharynx

Larynx

Primary Site

Tx-T3

T4 --\> Tumor of any size with direct extension to chest wall or skin Tx - T3 --\> any tumor not classified as T4

Primary tumor classification

N0 - tumor cells absent from regional lymph nodes N1 - regional lymph node metastasis present; (at some sites; tumor spread to closest or small number of regional lymph nodes)

Lymph node status

15 subjects consented, one withdrew before receiving study treatment and was excluded from analysis

Dr. Johnny Kao

Dose Level 1: Patients administered 150mg Erlotinib daily and 200mg Celecoxib twice daily

Celecoxib 200mg

Dose Level 2: Patients administered 150mg Erlotinib daily and 400mg Celecoxib twice daily

Celecoxib 400mg

Dose Level 3: Patients administered 150mg Erlotinib daily and 600mg Celecoxib twice daily

Celecoxib 600mg

Erlotinib and celecoxib were administered orally

Toxicity

Complete Response(CR)

Pathologic partial response (pPR)

Progressive disease (PD)

No evidence of disease (NED)

Clinical Response

free of disease

isolated locoregional progression

isolated distant progression

both locoregional and distant progression

no evidence of disease, died of comorbid illness

Locoregional Progression

locoregional control

progress-free survival

overall survival rates

long term toxicity

Locoregional Control, Progression-free Survival, Overall Survival and Late Toxicity

Overall Study

Nervous System Diseases

Diffuse Intrinsic Pontine Glioma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Brain Stem Neoplasms

Infratentorial Neoplasms

Starting dose of 24 Gray (Gy) in 2 Gy fractions.

Radiation Therapy

Susan L. McGovern, MD

The goal of this clinical research study is to find a safe dose of radiation that can be given to patients with brainstem glioma who have already received radiation therapy.

You will receive photon radiation therapy. This type of radiation is similar to the radiation you have already had. Conformal radiotherapy or intensity modulated radiotherapy (IMRT) will be used to try to treat the tumor while affecting as little of the surrounding normal tissue as possible.

Radiation Therapy Administration:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of radiation therapy based on when you join this study. Three (3) dose levels of radiation therapy will be tested. Three (3) participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will be randomly assigned (as in the roll of dice) to one of the dose levels, and the assignment will also depend on how the previous participants have done. Participants will not be assigned to one of the higher 2 of the 3 dose levels unless the lower dose level is found to be tolerable. The first and second groups will receive 12 treatments and the third group will receive 14 treatments (Monday through Friday for about 2½ weeks). Your doctor will tell you how many treatments you will receive.

You may be given drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Study Visits:

About 2-4 days before you start radiation therapy, you will have a simulation. During the simulation session, a mask will be made of your face and head to keep you still. You will also have a computed tomography (CT) scan. This process allows the radiation planning to take place. Sedation by an anesthesiologist (anesthesia doctor) will be used if needed for young children to allow the radiotherapy to be delivered safely.

One (1) time a week for 3 weeks, and then 1 time a month (30 days +/- 10 days) for 2 months or unless the disease gets worse:

* You will have a neurological exam.
* Your performance status will be recorded.
* You will fill out the quality-of-life questionnaire.
* You will be asked about any side effects you may have had.

You will have a magnetic resonance imaging (MRI) scan of the brain within 1 month after joining the study.

Length of Treatment:

You may continue receiving radiation therapy for 12 or 14 treatments. You will no longer be able to receive radiation therapy if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-up Visits:

One (1) month after you finish radiation therapy, at 6-8 weeks, then every 2-3 months after that from then on, you will have an MRI scan to check the status of the disease. The MRI scan will include advanced imaging to learn if the tumor has come back or if there is brain tissue damage from the radiation. With this type of imaging, a temporary infusion line with a bigger than standard size needle will be inserted to your vein if you do not already have a power port-a-cath in place. This may take between 20-30 minutes.

This is an investigational study. Radiation therapy in this study is delivered using FDA-approved and commercially available methods. It is investigational to find the best dose of radiation therapy to use for repeat radiation therapy.

Up to 30 participants will be enrolled in this study.

Diffuse Intrinsic Pontine Glioma (DIPG) Reirradiation (ReRT)

Phase I/II Study of Reirradiation of Recurrent or Progressive Brainstem Glioma

Optimal dose level among three RT dose levels, defined in terms of the biologically equivalent dose (BED). The BED is given by the formula BED = (Total Dose)\*(1 + d/3), denoting d = dose/fraction, with the constant 3 corresponding to brain tissue.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Pelvic Neoplasms

Ablative reirradiation of 50 Gy in 5 fractions (5 sessions) that will occur once per day, either for 5 days in a row, or every other day.

Reirradiation

Michael Chuong, M.D.

Carolina Rojas

Michael Chuong, MD

This research study will enroll people who have cancer in their abdomen or pelvis that was treated previously with radiation therapy. The purpose of this research study is to test the safety and possible harms of treating tumors in these regions with another round of radiation therapy, called reirradiation or "reRT." The researchers want to find out what effects (good and bad) reRT has in people with cancer in the abdomen and pelvis.

Ablative Stereotactic MR-Guided Adaptive Reirradiation

Phase 1 Trial of Ablative Stereotactic MR-Guided Adaptive Reirradiation for Abdominal and Pelvic Tumors

Number of participants who experience Grade 3 or higher acute toxicity \[graded per Common Terminology Criteria for Adverse Events (CTCAE)\] possibly, probably, or definitely related to reRT.

Number of participants who experience Grade 5 toxicity (graded per CTCAE) possibly, probably, or definitely related to reRT.

FFLP is defined as the duration of time from baseline to progressive disease (PD) in the re-irradiated lesion or death of any cause, whichever occurs first. Response to treatment will be assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

OS is defined as the defined as the duration of time from baseline to death of any cause, or date of last follow-up, whichever occurs first.

Number of participants who experience Grade 3 or higher acute toxicity \[graded per Common Terminology Criteria for Adverse Events (CTCAE)\] possibly, probably, or definitely related to reRT that occurs at least 90 days after reRT therapy has ended.

QOL will be assessed using the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire. The FACT-G is a 27-item questionnaire measuring physical, social, emotional, and functional well-being. All questions in the FACT-G use a 5-point rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 4 = Very much), with a possible range of 0-108 points. Negatively worded items are reverse scored prior to summing so that higher scores indicate better QOL.

Baptist Health Foundation

Baptist Health South Florida

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Disease Attributes

Neoplasms, Squamous Cell

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Reirradiation 1.2 Gy BID for 5 days a week for 5 weeks with MK-3475 (Keytruda, pembrolizumab) 200mg intravenous every 3 weeks until 3 months post completion of reirradiation.

Reirradiation 1.2 GY BID 5 days a week for 5 weeks.

MK-3475 will be given at 200mg intravenous every 3 weeks starting day one of reirradiation and will be continued once every 3 weeks until 3 months post completion of reirradiation. Further continuation of MK-3475 will be determined by response evaluation at 3 months post completion of reirradiation

MK-3475

Dan Zandberg, MD

Eligible participants with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck will be treated with reirradiation combined with anti-PD-1 mAb MK-3475 (generic name: pembrolizumab, trade name Keytruda®).

Each participant will undergo screening and then be treated with reirradiation with 1.2 Gy BID, 5 days a week (weeks 1-5). MK-3475 (generic name: pembrolizumab, trade name Keytruda®) will be given at 200mg intravenous every 3 weeks starting day one of reirradiation and will be continued in all participants until 3 months post completion of reirradiation, at which time a PET/CT will be done to evaluate response. Participants with progressive disease (PD) will be taken off MK-3475 and followed for survival. Participants that have a complete response (CR) will be followed clinically and radiographically, and if disease recurs may be eligible to be retreated with MK-3475 for up to one year. Participants with partial response (PR) or stable disease (SD) will continue treatment with MK-3475 for up to two years unless one of the following occurs:

* documented disease progression
* unacceptable adverse event(s)
* intercurrent illness that prevents further administration of treatment
* investigator decision to withdraw the subject
* withdrawal of consent
* pregnancy
* noncompliance
* administrative reasons (i.e. trial is closed prematurely).

Participants who have not progressed at completion of 24 months of therapy will be observed, but may be eligible for 1 year of retreatment with MK-3475 if they develop recurrence/progression and qualify for retreatment as detailed in the protocol,and if the trial is still ongoing.

Reirradiation With Pembrolizumab in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck

A Phase II Trial of Reirradiation Combined With Open Label Pembrolizumab in Patients With Locoregional Inoperable Recurrence or Second Primary Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Number of months from the date of initiation of treatment to the date of progression of disease or death (whichever occurs first). Progressive disease, per RECIST 1.1, is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Overall response rate, which will be determined per RECIST 1.1, is defined as the percentage of the patients who have a either Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, or, Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The patient's best overall response rate defined as the best response recorded from the start of the treatment until disease progression will be recorded.

Number of months from initiation of treatment to progression of disease within the radiation field.Progressive disease, per RECIST 1.1, is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Number of months from first treatment until death. Patients who are alive will be censored at the last date of patient contact.

Patient reported outcomes will be measured using EORTC QLQ-C30 and EORTC QLQ-H\&N35 questionnaires. This tool contains 30 items. It measures 5 functional dimensions (physical, role, cognitive, social, emotional), 6 single items (appetite loss, constipation, dyspnea, financial impact, sleep disturbance, diarrhea), 3 symptom items (fatigue, pain, nausea/vomiting) and a global health and quality of life scale. Scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

The percentage of patients that have achieved a complete response, partial response, and stable disease as defined by RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, or Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Image Guided Reirradiation of High-grade Glioma	NCT02025231	Malignant Gliom... Glioblastoma	External beam r...	18 Years -	Rigshospitalet, Denmark
Erlotinib, Celecoxib and Reirradiation for Recurrent Head and Neck Cancer	NCT00970502	Cancer of the P... Cancer of the L... Cancer of the N... Paranasal Sinus... Cancer of the H...	erlotinib + cel...	18 Years -	Icahn School of Medicine at Mount Sinai
Diffuse Intrinsic Pontine Glioma (DIPG) Reirradiation (ReRT)	NCT01469247	Brain Cancer	Radiation Thera...	- 17 Years	M.D. Anderson Cancer Center
Ablative Stereotactic MR-Guided Adaptive Reirradiation	NCT06397573	Abdominal Cance... Pelvic Cancer	Reirradiation	18 Years -	Baptist Health South Florida
Reirradiation With Pembrolizumab in Locoregional Inoperable Recurrence or Second Primary Squamous Cell CA of the Head and Neck	NCT02289209	Recurrent Head ... Carcinoma, Squa...	Reirradiation MK-3475	18 Years -	University of Pittsburgh
Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study	NCT05904119	First Progressi...	Lomustine Reirradiation	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Radiotherapy & Total Neoadjuvant Therapy for Recurrent Rectal Cancer in Previously Irradiated Patients, an Italian Association for Radiotherapy and Clinical Oncology (AIRO)-GI Platform: a Multi-centre Prospective Observational Study	NCT05984576	Rectal Neoplasm	Reirradiation	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IMRT Combined With Toripalimab in Unresectable Locally Recurrent Nasopharyngeal Carcinoma.	NCT03854838	Nasopharyngeal ... Nasopharyngeal ... Nasopharyngeal ... Head and Neck N...	Tolipalimab Reirradiation	18 Years - 65 Years	Sun Yat-sen University
Retrospective Cervical Cancer Oligo States (Recurrence, Metastasis) Multicentre Outcomes Study	NCT06150222	Cancer, Cervica... Recurrence Metastasis	Concurrent Chem...	18 Years - 100 Years	Erasmus Medical Center
DAHANCA 37. Re-irradiation With Proton Radiotherapy	NCT03981068	Head and Neck N...	Re-irradiation	18 Years -	Danish Head and Neck Cancer Group

Spots Global Cancer Trial Database for reirradiation