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Neoplasms

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Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Antineoplastic Agents, Immunological

Cetuximab will be administered for 3 weekly doses commencing one week prior to stereotactic radiosurgery treatment as follows: \* Cetuximab 400 mg / m2 day -7 (1 week prior to initiation of radiosurgery) \* Cetuximab 250 mg/m2 days 0 and +8 (i.e. during the first and second week of fractionated stereotactic radiosurgery) Cetuximab will be administered at 400 mg/m2 IV over 120 minutes on day -7 (loading dose) and 250 mg/m2 IV on days 0 and 8 during the course of stereotactic radiosurgery.

Fractionated stereotactic radiosurgery, 8.0 Gy per fraction for 5 fractions (total: 40.0 Gy)

Stereotactic radiosurgery

David A Clump, MD

This trial examines survival and toxicity in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN) treated with radiosurgery and cetuximab and to evaluate the acute and late toxicities associated with the above therapy.

Squamous cell carcinoma of the head and neck is the sixth most common malignancy worldwide with approximately 500,000 cases worldwide yearly. There were an estimated 39,250 new cases and 11,000 deaths in the United States in 2005 (Jemal 2005, Spitz MR). Despite major improvements in the treatment of SCCHN in recent years which include the introduction of concurrent chemoradiotherapy as an effective primary or postoperative therapy, the five-year survival rate for patients with SCCHN in the United States and other developed countries remains poor as nearly 50-60% of these patients will die as a direct result of recurrent locoregional disease. This study aims to determine the 1-year progression-free survival (PFS) of previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN) treated with radiosurgery and cetuximab and to evaluate the acute and late toxicities associated with the therapy.

Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck

Progression (response as assessed by subjective interpretation of the first PET-CT) per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) was defined as greater than 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum and longest diameter recorded since the baseline measurements or the appearance of 1 or more new lesion(s). If the measurable disease was restricted to a solitary lesion, the protocol specified that neoplastic nature should be confirmed by cytology and histology.

Progression was defined as greater than 20% increase in the sum of the longest diameters of target lesions, per Response Evaluation Criteria in Solid Tumors (RECIST v1.0), taking as reference the smallest sum and longest diameter recorded since the baseline measurements or the appearance of 1 or more new lesion(s). If the measurable disease was restricted to a solitary lesion, the protocol specified that neoplastic nature should be confirmed by cytology and histology.

Number of months patients remaining alive after study treatment.

Response by number and percentage of patients assessed by subjective interpretation of the first PET-CT. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Glucose metabolism was assessed by FDG PET. FDG uptake reflects the tissue glucose metabolism and is usually high in high-grade tumors and relatively low in low-grade tumors.

Changes in tumor hypoxia (tumor cells deprived of oxygen) as a result of Stereotactic radiosurgery (SRS) through assessment by pre-and post-treatment fluorodeoxyglucose (FDG)- and fluoromisonidazole (FMISO)-PET.

Percentage of patients that reported stable and/or improved of quality of life after SBRT as indicated by a quantitative increase or maintenance in overall score. Quality of Life was assessed by longitudinal collection of the University of Washington Quality of Life Registry (UW-QoL-R) survey data, both pre- and post-SBRT. Patients completed the previously validated UW-QoL-R survey at enrollment and again after SBRT. UW-QoL-R measures patient reported QoL in 12 head and neck-specific and 3 global health domains, using a single Likert-scale question with an assigned score of 0 to 100 with 100 representing normal function.

David A. Clump, MD, PhD

Associate Professor of Medicine

Adverse Events and Serious Adverse Events determined using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Adverse Events were Grade 1 and Grade2 toxicities; Serious Adverse Events were Grade 3 and Grade 4 toxicities.

All-Cause Mortality: At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression; 88% deceased at time of final analysis.

Cetuximab: Cetuximab will be administered for 3 weekly doses commencing one week prior to stereotactic radiosurgery treatment as follows: \* Cetuximab 400 mg / m2 day -7 (1 week prior to initiation of radiosurgery) \* Cetuximab 250 mg/m2 days 0 and +8 (i.e. during the first and second week of fractionated stereotactic radiosurgery) Cetuximab will be administered at 400 mg/m2 IV over 120 minutes on day -7 (loading dose) and 250 mg/m2 IV on days 0 and 8 during the course of stereotactic radiosurgery.

Stereotactic radiosurgery: Fractionated stereotactic radiosurgery, 8.0 Gy per fraction for 5 fractions (total: 40.0 Gy)

Cetuximab and Stereotactic Radiosurgery

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Prior surgery

Prior chemotherapy

Received prior epidermal growth factor receptor (EGFR)

A scale for indicating a patient's functional level: 0 asymptomatic - 1 Symptomatic, fully ambulatory - 2 Symptomatic, in bed - 50% of the day - 3 Symptomatic, in bed \> 50% of the day but not bedridden - 4 Bedridden - 5 Dead.

Zubrod performance status

Barbara Stadterman, Regulatory Supervisor; ClinicalTrials.gov Admin

Patients that received study therapy and were evaluable for response to treatment.

1-year Local Progression-free Survival (PFS)

1-year Locoregional Progression-free Survival (PFS)

1-year Distant Progression-free Survival (PFS)

1-year Progression-free Survival (PFS)

Overall Survival (OS)

Complete response

Partial Response

Stable disease

Disease progression

Overall Response (OR)

Patients that received study therapy and were evaluable for response and by FDG PET.

Changes in Tumor Glucose Metabolism

At the time of this study, PMISO could not be readily obtained due to its relatively short half-life and unforeseen inability to procure this radioisotope locally. Thus, to prevent delay in treating aggressive cancer, F-MISO scans were not performed.

Changes in Tumor Hypoxia.

Patients that received study therapy and were able to complete Quality of Life assessments, who reported stable or improved quality of life.

Quality of Life (QoL)

Overall Study

Nervous System Diseases

Brain Diseases

Central Nervous System Diseases

Patients undergo FSRS over 3 or 5 daily sessions.

Single Fraction Stereotactic Radiosurgery

Fractionated Stereotactic Radiosurgery

Quality-of-Life Assessment

Questionnaire Administration

Paul D. Brown, MD

This phase III trial studies how well single fraction stereotactic radiosurgery works compared with fractionated stereotactic radiosurgery in treating patients with cancer that has spread to the brain from other parts of the body and has been removed by surgery. Single fraction stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Fractionated stereotactic radiosurgery delivers multiple, smaller doses of radiation therapy over time. This study may help doctors find out if fractionated stereotactic radiosurgery is better or worse than the usual approach with single fraction stereotactic radiosurgery.

PRIMARY OBJECTIVES:

I. To ascertain if time to surgical bed failure is increased with fractionated stereotactic radiosurgery (FSRS) compared to single-fraction stereotactic radiosurgery (SSRS) in patients with resected brain metastasis.

SECONDARY OBJECTIVES:

I. To ascertain if there is better emotional well-being at 9 months as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-BR) in patients with resected brain metastasis undergoing FSRS compared to SSRS (Primary quality of life \[QOL\] objective).

II. To ascertain whether there is improved overall survival in patients with resected brain metastases who undergo FSRS compared to patients who receive SSRS.

III. To ascertain in patients with resected brain metastases whether there is improved overall QOL as assessed by the FACT-BR and Linear Analog Self-Assessment (LASA) in patients who receive FSRS compared to patients who receive SSRS (Secondary QOL objective).

IV. To compare the functional independence in patients who receive FSRS to patients who receive SSRS.

V. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions, including the potential impact of immunotherapy and targeted therapy.

VI. To compare rates of radiation necrosis at 12 months in patients who receive FSRS to patients who receive SSRS.

VII. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local, distant brain failure, local leptomeningeal disease, widespread leptomeningeal disease) in patients who receive FSRS compared to patients who receive SSRS after resection of brain metastasis.

VIII. To ascertain in patients with resected brain metastases whether there is increased time to whole-brain radiotherapy (WBRT) in patients who receive FSRS compared to patients who receive SSRS.

IX. To determine in long-term survivors (patients who are alive more than 12 months from time of randomization) whether there is better emotional well-being and overall QOL as assessed by the FACT-BR and LASA in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Secondary QOL objective).

X. To assess for differences in CNS failure patterns (surgical, local, distant brain failure, leptomeningeal disease) as well as radiation necrosis rates as assessed by central review in patients who receive FSRS compared to patients who receive SSRS after resection of a brain metastasis.

XI. To ascertain in patients with resected brain metastases whether there is improved QOL as assessed by all other total and individual FACT-BR and LASA items and subscale values in patients who receive FSRS compared to patients who receive SSRS (Exploratory QOL objective).

XII. To determine in patients with resected brain metastases whether there is less cognitive progression in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Exploratory cognitive objective).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SSRS over 1 session.

ARM II: Patients undergo FSRS over 3 or 5 daily sessions.

After completion of study, patients are followed up at 30 days, at 3, 6, 9, 12, 16, and 24 months, then every 6 months until 5 years from randomization.

Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease

Phase III Trial of Post-Surgical Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS for Resected Metastatic Brain Disease

Surgical bed control is defined as the absence of new nodular contrast enhancement in the surgical bed. In other words, a surgical bed recurrence-free survival (SB-RFS) event is defined as radiographic evidence of a new contrast-enhancing lesion (specifically any new progressive enhancing nodularity) at the site of the surgical resection. Will use a stratified log-rank test that compares and will report the median SB-RFS times between the single fraction stereotactic radiosurgery (SSRS) and fractionated stereotactic radiosurgery (FSRS) arms while adjusting for the stratification factors.

The average change from baseline to 9 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale will be compared between randomization arms.

The average change from baseline to 9 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score will be compared between randomization arms.

The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score will be compared between randomization arms.

Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 12 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale for the long-term survivors will be compared between randomization arms.

Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 12 months in the Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score for the long-term survivors will be compared between randomization arms.

Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The average change from baseline to 9 months in the Linear Analog Self-Assessment (LASA) overall total score for the long-term survivors will be compared between randomization arms.

The duration of Karnofsky Performance Status (KPS) functional independence will be the time to when the KPS scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of KPS functional independence will be reported and compared between randomization arms.

The duration of Barthel Activities of Daily Living (ADL) functional independence will be the time to when the ADL scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of ADL functional independence will be reported and compared between randomization arms.

Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The duration of Karnofsky Performance Status (KPS) functional independence will be the time to when the KPS scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of KPS functional independence for long-term survivors will be reported and compared between randomization arms.

Long-term survivors defined as patients who are alive more than 12 months from time of randomization. The duration of Barthel Activities of Daily Living (ADL) functional independence will be the time to when the ADL scores per patient decrease below their baseline level and will be compared between treatment arms by the logrank test. Median durations of ADL functional independence for long-term survivors will be reported and compared between randomization arms.

Overall survival time will be compared between the treatment arms using a stratified log-rank test. If the proportional hazards assumption is violated, a restricted means analysis will be used to compare overall survival between the two treatment arms. Median survival times per treatment arms will be reported.

The Common Terminology Criteria for Adverse Events version 5.0 will be used. The proportion of patients experiencing any adverse event will be compared between the two treatment arms using a chi-square (or Fisher's exact test, if more appropriate).

The proportion of patients with radiation necrosis within 24 months from of starting treatment will be compared between the treatment arms with a chi-square test (or Fisher's exact test if more appropriate).

Time until whole-brain radiotherapy (WBRT) will be compared between the treatment arms using a stratified log-rank test. Median time until WBRT per treatment arms will be reported.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Neoplasm Metastasis

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

SRS SBRT CyberKnife Trilogy True Beam Radiosurgery

Steve Burton, MD

This is a research trial that seeks to break up the total radiation dose into multiple smaller radiation treatments, termed fractionated stereotactic radiosurgery (FSRS) which may make the treatment feasible. Fractionated sterotatcic radiation, the risks of FSRS, and possible costs will be described later in this document. This clinical trial is for people who have had no prior whole brain radiation.

Fractionated Stereotactic Radiosurgery for Large Brain Metastases

PHASE I STUDY OF FRACTIONATED STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES

The proportion patients experiencing DLT at each dose; toxicities will be tabulated by category and grade. The dose-toxicity function, describing the probability of DLT at each dose, will be estimated using logistic regression, along with likelihood ratio profile confidence intervals.

Proportion of patients with local control at each dose. Local control is defined as stable disease (SD), partial response (PR), or complete response (CR) in the target lesion, per RECIST v1.1. Complete Response (CR): the disappearance of a target lesion. 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. Stable Disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.

Proportion of patients having local failure (progressive disease (PD)) within the target lesion. Per RECIST v1.1: Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as a 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).

Functional Assessment of Cancer Therapy - Brain (FACT-Br) is a 50 item, self-administered questionnaire used to assess Quality of Life, including, Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The assessment takes 10-15 minutes to completed and is scored using a 5 point Likert-type scale. Scores range from 0-250, with higher scores indicating better Quality of Life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck	NCT01104922	Squamous Cell C...	Cetuximab Stereotactic ra...	18 Years -	University of Pittsburgh
Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease	NCT04114981	Metastatic Mali...	Single Fraction... Fractionated St... Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology
Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease	NCT04114981	Metastatic Mali...	Single Fraction... Fractionated St... Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology
Fractionated Stereotactic Radiosurgery for Large Brain Metastases	NCT02054689	Large Brain Met...	Fractionated St...	18 Years -	University of Pittsburgh
Fractionated Stereotactic Radiosurgery for Large Brain Metastases	NCT02054689	Large Brain Met...	Fractionated St...	18 Years -	University of Pittsburgh
Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck	NCT01104922	Squamous Cell C...	Cetuximab Stereotactic ra...	18 Years -	University of Pittsburgh
Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck	NCT01104922	Squamous Cell C...	Cetuximab Stereotactic ra...	18 Years -	University of Pittsburgh
Single Fraction Stereotactic Radiosurgery Compared With Fractionated Stereotactic Radiosurgery in Treating Patients With Resected Metastatic Brain Disease	NCT04114981	Metastatic Mali...	Single Fraction... Fractionated St... Quality-of-Life... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for fractionated stereotactic radiosurgery