Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Adenocarcinoma

Adenocarcinoma of Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR (Stereotactic ablative body radiation). They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination). The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months. At Follow-Up treatment, patients will be contacted every 3 months for 9 months.

Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR radiation. The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months.

Patients will receive study drug for 10 weeks. They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination).

Stereotactic ablative body radiation

Saad Khan, MD

The purpose of this study is to see if Ceritinib can target ALK in non-small cell lung cancer and slow down cancer growth and prevent it from spreading.

This is an, open-label, two-cohort protocol designed to evaluate the activity of targeted therapy and SABR in ALK positive lung adenocarcinoma.

Cohort A will evaluate the combination in ALK-inhibitor naïve patients. Cohort B will evaluate the combination in patients who have received treatment with one prior ALK inhibitor.

Ceritinib will be administered to the patient until disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason including death.

The primary focus of this protocol is identifying response in ALK+ lung cancer patients. Patients with Ventana assay and Vysis FISH probe positive tumors will be treated. Evidence of ALK gene rearrangement will also be considered eligible for the trial.

Primary Objective:

Cohort A: Superiority of ceritinib + SABR median PFS compared to historical control of 10 months (expected to be 20 months)

Endpoint:

Cohort A Median PFS defined as time from initiation of ceritinib until disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason including death.

Primary:

Cohort B: Superiority of ceritinib + SABR median PFS compared to historical control of 7 months.

Endpoint:

Cohort B: Median PFS defined as time from initiation of ceritinib until disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason including death.

Secondary:

* Report Overall survival Overall survival
* Report Time to 2nd SABR Time from start of systemic therapy to first day of second course of SABR
* Report Time to 3rd SABR Time from start of therapy to first day of third course of SABR
* Report proportion of patients CR/PR/stable disease at 6 and12 months Number of patients with CR/PR/stable disease for 6 and 12 months after initiation

Safety:

-Demonstrate safety of ceritinib followed by SABR Describe toxicity and adverse events (CTCAE v.4) compared to historical controls.

Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma

Phase II Trial of Ceritinib in Combination With Stereotactic Ablative Radiation in ALK-rearranged Metastatic Lung Adenocarcinoma

Number of days until disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Overall survival is the percentage of participants alive at the given time point. OS is defined as the time to death from the start of drug therapy.

After the initial SABR to persisting lesions, if new lesions appear or if existing lesions enlarge but are amenable to SABR, patients will remain on study and listed as not having progressed. Time from start of systemic therapy to first day of second course of SABR

Time from start of therapy to first day of third course of SABR was measured.

Number of patients with CR/PR/stable disease for 6 months was measured by evaluating target lesions.

Complete Response (CR): Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.

Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Number of patients with CR/PR/stable disease for 12 months was measured by evaluating target lesions.

Complete Response (CR): Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.

Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.

Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Novartis Pharmaceuticals

University of Texas Southwestern Medical Center

Assistant Professor

Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR (Stereotactic ablative body radiation). They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination). The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months. At Follow-Up treatment, patients will be contacted every 3 months for 9 months.

Ceritinib: Patients will receive ceritinib at a dose of 750 mg (150 mg capsules times 5 capsules once a day) for 10 weeks. Patient will stop taking Ceritinib 72 hours before SABR radiation. The patient may start taking Ceritinib again 72 hours after radiation is complete. Patient will continue to take certinib for up to 8 months.

Stereotactic ablative body radiation: Patients will receive study drug for 10 weeks. They could get 1, 3 ,or 5 treatments on consecutive days with 18 hours between each treatment or every other day (doctor's determination).

ALK-inhibitor Naive Patients

Patients Recieved Prior ALK Inhibitor

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

1 patient withdrew consent before thier first scan.

Dr. Sawsan Rashdan

Progression Free Survival

Overall Survival

No patients received a second course of SABR

Time to 2nd Subsequent Stereotactic Ablative Radiation

Data was not collected due to early termination of the study since no participant received 3rd SABR.

Time to 3rd Subsequent Stereotactic Ablative Radiation (SABR)

Number of Patients With CR/PR/Stable Disease for 6 Months

Number of Patients With CR/PR/Stable Disease for 12 Months

Number of Participants With Adverse Events

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Pancrelipase

Pancreatin

50 Gy in five fractions SABR (once per day for 5 days) and use of the TTF system for 18 hours per day starting on the first day of SABR and continuing until abdominal disease progression

50 Gy in 5 fractions, once per day for 5 days

Stereotactic Ablative Body Radiation (SABR)

Participant will use the system for at least 18 hours per day starting on the first day of SABR until abdominal disease progression. Short treatment breaks are permitted for personal needs (such as to take a shower) and during radiation therapy. An additional treatment break is permitted for up to 48 hours every 21 days.

Tumor Treating Fields (TTF)

Michael Chuong, M.D.

Carolina Rojas

The purpose of this clinical trial is to determine whether using chemotherapy followed by stereotactic ablative body radiation therapy (SABR) and tumor treating fields (TTF) will slow tumor growth in people with locally advanced pancreas cancer. All participants will receive SABR therapy once per day for five days and use the TTF system for at least 18 hours per day starting on the first day of SABR until the tumor progresses or severe toxicity develops.

Stereotactic Body Radiation and Tumor Treating Fields for Locally Advanced Pancreas Cancer

Phase 2 Trial of Ablative MRI-guided Stereotactic Body Radiation Therapy and Tumor Treating Fields for Locally Advanced Pancreas Cancer

PFS is defined as the time from the initiation of study therapy to the first documented disease progression or death due to any cause, whichever occurs first

LC is defined as a response within the radiation target volume according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (i.e., percentage of participants with stable disease, partial response, or complete response).

LC is defined as a response within the radiation target volume according to RECIST) v1.1 criteria (i.e., percentage of participants with stable disease, partial response, or complete response).

DMFS is defined as the time from initiation of study therapy to the first radiographic confirmation of distant metastasis

OS is defined as the time from the initiation of study therapy to death due to any cause or date of last follow-up, whichever occurs first.

Quality of Life will be assessed using the Functional Assessment of Cancer Therapy - General (FACT-G), a 27-item questionnaire designed to measure four domains of QOL in cancer patients: physical, social, emotional, and functional well-being. Each domain has a scoring range of 0-28, for a combined total score of 0-108, where higher scores indicate better QOL.

All participants will be evaluable for toxicity from the time of their first treatment. All Grade 3+ toxicities \[according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0\] will be tracked, regardless of attribution to study treatment.

Location of recurrence is defined as the site(s) at the time of any first tumor recurrence: local only \[centroid of the recurrence within the planning target volume (PTV)\], distant only (centroid of the recurrence outside of the PTV), or local and distant.

The chemotherapy-free interval is defined as the duration of time from the initiation of study therapy to the date any chemotherapy is subsequently administered.

NovoCure Ltd.

Michael Chuong

Medical Director of Proton Therapy and Photon Therapy

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Behaviors and Mental Disorders

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Quality of Life

Stereotactic Ablative Body Radiation

Danny Vesprini, MD

Daniel Vesprini, MD

Prostate Stereotactic ablative body radiotherapy (SABR) is an established technique that delivers radiation in a non-invasive approach for men with prostate cancer. The treatment regimen is given in total of 5 fractions with one treatment per day at every other day or weekly sessions. Ultra-hypofractionated radiotherapy (UHRT) is an emerging monotherapy for localized prostate cancer however, several trials have observed demonstrating superior biochemical control of a two-fraction (HDR) over single-fraction approach. The study aims to compare an experimental shorter course of prostate ultra-hypofractionated radiotherapy (UHRT) that will deliver what is expected to be an equivalent amount of radiation as given in the standard 5 treatment regimen. UHRT is given in 2 treatments with one treatment a week for 2 consecutive weeks.

Ultra-hypofractionated radiotherapy (UHRT) is an emerging monotherapy for localized prostate cancer. From a radiobiological standpoint, fewer fractions and higher doses per fraction takes greater advantage of the low α/β ratio of prostate cancer to improve the therapeutic ratio, most recently estimated at 1.6 based on 14 randomized controlled trials.Highly conformal delivery of large doses per fraction can be achieved with either high dose rate (HDR) brachytherapy or with stereotactic ablative radiotherapy (SABR).

Several trials have explored HDR as monotherapy, from 6-fractions to a single-fraction approach. Sunnybrook recently published a randomized trial of HDR monotherapy demonstrating superior biochemical control of a two-fraction over single-fraction approach. These and other data have informed the design of a phase III randomized controlled trial comparing two-fraction HDR monotherapy to low dose rate (LDR) brachytherapy in patients with intermediate risk prostate cancer (NCT02960087) coordinated by the Canadian Clinical Trails Group (PR19). The investigators have shown that 2 fraction SABR has equivalent efficacy and tolerability to 2 fraction HDR but SABR does not require general anesthesia, is less invasive and cheaper.

UHRT is also supported by phase III data, including a large non-inferiority randomized trial (HYPO-RT-PC) demonstrating similar biochemical control with a 7-fraction versus conventionally-fractionated regimen. The non-inferiority PACE-B trial comparing 5-fraction SABR to conventionally-fractionated or moderately hypofractionated RT has demonstrated similar acute toxicity with use of contemporary SABR planning techniques. Sunnybrook has also conducted several iterative clinical trials testing increasingly hypofractionated external beam radiotherapy. The investigators observed in parallel cohort studies that 5 fractions of UHRT and 2 fractions of UHRT with a patented immobilization device (GU-Lok) had equal effectiveness but better tolerability with the 2 fraction technique. As this was a post hoc analysis, this study aims to validate those findings.

Improving Sexual Quality of Life - Randomized Trial of Two vs Five MRI Guided SABR Treatments for Prostate Cancer

Improving Sexual Quality of Life - A Phase 2 Randomized Controlled Trial of Two Versus Five Stereotactic MRI-Guided Ablative Radiotherapy Treatments for Prostate Cancer

Expanded Prostate Cancer Index Composite questionnaires will be scored and analyzed to determine change in Quality of life function from baseline

Incidence of acute Gastrointestinal (GI) and Genitourinary (GU) complications using CTCAE v4

Proportion of patients with 4 year PSA value of \<0.4 ng/ml

5 year biochemical failure rates using Phoenix definition (as nadir PSA +2ng/mL)

Analysis of prostate patients requiring salvage treatment using Androgen Deprivation Therapy, surgery or brachytherapy

Analysis of patient reported outcome using EQ-5D-5L

Analysis of patient reported outcome using PORPUS-U

Prostate Cure Foundation

Sunnybrook Health Sciences Centre

Radiation Oncologist

Symptoms and General Pathology

Neoplasm Metastasis

Liver Neoplasms

Liver Diseases

Primary Liver Cancer

Hematinics

Liver Extracts

All patients will receive liver SABR. Kilovoltage Intrafraction Monitoring (KIM) tracking will be trialed during mock treatment. If KIM is successful, it will be used throughout treatment. If unsuccessful, cone beam CT will be used instead.

KIM is a novel intrafraction real-time tumour localization method. It involves a single gantry-mounted kV x-ray imager acquiring 2D projections of implanted fiducial markers. 3D positions are then reconstructed by maximum likelihood estimation of a 3D probability density function.

Kilovoltage Intrafraction Monitoring

Tim Wang, Dr

Primary and secondary liver cancer patients will receive liver SABR with or without KIM intervention.

This is a single arm, phase II, two stage study designed to evaluate cancer targeting accuracy, treatment outcomes and treatment efficiency in 46 patients eligible for SABR for either primary or secondary liver malignancy with the incorporation of KIM.

Liver Ablative Radiotherapy Utilising Kilovoltage Intrafraction Monitoring (KIM)

LARK: Liver Ablative Radiotherapy Utilising Kilovoltage Intrafraction Monitoring (KIM)

Anonymised data will be made available to researchers upon request, once evidence of ethical approval has been provided.

Isodose distributions and dose volume histograms for each session will be calculated with KIM corrections as treated, and estimated without KIM corrections. The planning CT scan will be used for this assessment

The time taken for the KIM treatments compared with the time taken for similar treatments from previous patients, accounting for the difference in the time and number of patient images acquired and the time taken to adjust the patient's position during treatment

The KIM procedure adds radiation dose with the kilovoltage images. However, there may be fewer volumetric cone beam computed tomography (CBCT) scans acquired. This difference in dose will be estimated and analysed

The clinical target volume (CTV) to planning target volume (PTV) margin with and without KIM will be recorded and analysed.

Isodose distributions and dose volume histograms for each session will be calculated with KIM corrections as treated, and estimated without KIM corrections. The intratreatment CBCT scans will be used for this assessment.

Difference between dose delivered using KIM with or without MLC tracking

Proportion of local failures at two years for patients treated as assessed using modified RECIST criteria

The proportion of grade 3 or higher toxicities, assessed using CTCAE v4.03

To compare change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 (Version 3)) from baseline at completion of radiation therapy and at 6 weeks, 3, 6, 12, 18 and 24 months post-radiation therapy. The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). The questionnaire will be self-administered and will be given in patient's mother tongue.

To compare change in Quality of Life related to hepatocellular carcinoma (HCC) as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Hepatocellular Carcinoma 18 Module (EORTC QLQ-HCC) from baseline at completion of radiation therapy and at 6 weeks, 3, 6, 12 and 18 months post-radiation therapy. The questionnaire will be self-administered and will be given to patients proficient in English. EORTC-QLQ-HCC18: includes HCC-specific symptoms or problems. Questions used 4-point Likert scale from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Scores averaged and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma	NCT02513667	ALK-positive No...	Ceritinib Stereotactic ab...	18 Years -	University of Texas Southwestern Medical Center
Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma	NCT02513667	ALK-positive No...	Ceritinib Stereotactic ab...	18 Years -	University of Texas Southwestern Medical Center
Stereotactic Body Radiation and Tumor Treating Fields for Locally Advanced Pancreas Cancer	NCT05679674	Pancreas Cancer Locally Advance... Locally Advance...	Stereotactic Ab... Tumor Treating ...	18 Years -	Baptist Health South Florida
Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma	NCT02513667	ALK-positive No...	Ceritinib Stereotactic ab...	18 Years -	University of Texas Southwestern Medical Center
Improving Sexual Quality of Life - Randomized Trial of Two vs Five MRI Guided SABR Treatments for Prostate Cancer	NCT05600400	Prostate Cancer Cancer of Prost... Prostate Adenoc...	Stereotactic Ab...	18 Years -	Sunnybrook Health Sciences Centre
Liver Ablative Radiotherapy Utilising Kilovoltage Intrafraction Monitoring (KIM)	NCT02984566	Liver Cancer	Kilovoltage Int...	18 Years - 85 Years	University of Sydney

Spots Global Cancer Trial Database for stereotactic ablative body radiation