Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients undergo extreme hypofractionated radiation therapy (Intensity modulated radiation therapy, Volumetric modulated arc therapy, Image guided radiation therapy) once a week over 28 days

Patients undergo extreme hypofractionated radiation therapy (Intensity modulated radiation therapy, Volumetric modulated arc therapy, Image guided radiation therapy) other 9 days.

Minimize radiation doses to surrounding area

Intensity modulated radiation therapy

Volumetric modulated arc therapy

Follow target by the use of fiducial markers and ERB

Image guided radiation therapy

Thomas Zilli, Dr

RATIONALE: It is not yet known whether extreme hypofractionation is equally safe and effective than standard radiation therapy in treating prostate cancer.

PURPOSE: This protocol presents a randomised phase II study aiming to investigate the tolerance and disease control of extreme hypofractionated Radiation Therapy for prostate cancer.

This protocol presents a randomised phase II study aiming to investigate the tolerance and disease control of extreme hypofractionated RT for prostate cancer by delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules: either over 9 days (study A), or over 28 days once-a-week, the same week-day (study B).

The total dose and fractionation schedules have been chosen based on the assumption of their isoeffectivity regarding potential late rectal effects to be expected with a maximum equivalent dose of 74 Gy in 2 Gy fractions and assuming an alpha/beta = 3 Gy for the rectum.

In both arms, the prescribed dose per fraction to the urethra and the surrounding transitional zone will be dropped from 7.25 Gy to 6.5 Gy with a simultaneous integrated boost (SIB) technique. A dose of 5 x 6.5 Gy is equivalent to 31 x 2 Gy assuming an alpha/beta = 3 Gy for the urethra and equivalent to 37 x 2 Gy assuming an alpha/beta = 1.5 Gy for microscopic tumour foci in the transitional zone surrounding the urethra. The two treatment regimens chosen will each be the object of a separate phase I-II study covered by the same protocol and performed in parallel by the participating centres. Randomised assignment to either of the two studies will be introduced to avoid selection bias in treatment assignment within each centre.

OBJECTIVES:

Primary

* To determine the risk of urinary, rectal and sexual acute and late toxicities rates in patients receiving two different time schedules of extreme hypofractionated radiation therapy

  • Secondary
* To determine the Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25) in patients receiving two different time schedules of extreme hypofractionated radiation therapy
* To determine the rate of local failure
* To determine in the two study arms the biochemical disease-free survival bDFS rate
* To determine in the two study arms the metastases-free survival rate
* To determine in the two study arms the disease-specific survival rate

OUTLINE:

This is a multicenter study.

Patients undergo extreme hypofractionated radiation therapy for prostate cancer by delivering 5 x 7.25 Gy = 36.25 Gy over two alternative time schedules:

Experimental Arm A: Over 9 days. Experimental Arm B: Over 28 days once-a-week, the same week-day. All patients will be followed up for at least 18 months to contribute to the analysis of the main endpoints of the study. With reference to the secondary endpoints, follow-up will be extended to 10 years.

Stopping rule: In order to avoid exposure of patients to a treatment that may be unsafe, acute GI and GU toxicity will be continuously monitored with the purpose of assisting in the decision of possibly interrupt recruitment in case of an alarming frequency.To this purpose, the procedure of Ivanova et al., 2005 will be applied.

5 x 7.25 Gy delivery in 2 alternative time Schedule: over 9 days every other treatment or over 28 days once a week

Hypofractionated Radiation Therapy in Prostate Cancer

Stereotactic Body Radiation Therapy for cT1c - cT3a Prostate Cancer With a Low Risk of Nodal Metastases (≤ 20%, Roach Index): a Novalis Circle Phase II Prospective Randomized Trial

No plan to share participant data for now

Tolerance to treatment (urinary, rectal, sexual): Acute (up to 90 days) and late (up to 5 years) toxicity follow-up according to NCI CTCAE version 3.0

Quality of life (EORTC QLQ-C30, Prostate cancer module EORTC QLQ-PR25)

Assessed by digital rectal examination (DRE). MRI or PET-CT with choline or acetate may be a confirmatory option. Biopsy confirmation is required for those patients with exclusive local failures and candidates for local salvage.

Outcomes 3 or 4 - investigations PET-CT choline

Alive/dead status, date and cause of death and prostate cancer disease status (outcomes 3/4 and 5).

Thomas Zilli

Neoplastic Processes

Single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.

Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.

Hui-Kuo Shu, MD, PhD

Brain metastases are the most common adult intracranial tumor, occurring in approximately 10% to 30% of adult cancer patients, and represent an important cause of morbidity and mortality. The most widely used treatment for patients with multiple brain metastases is whole brain radiation therapy (WBRT). The use of WBRT after resection or stereotactic radiosurgery (SRS) has been proven to be effective in terms of improving local control of brain metastases.

RapidArc (RA) (Varian Medical Systems, Palo Alto, CA) is a new method of delivering radiation that uses "arcs" to deliver highly conformal intensity modulated three dimensional dose distributions. The purpose of this investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis.

Given the limitations of the SRS boost technique, the purpose of our investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis. In this study, we plan to assess the tolerability of using volumetric modulated arc therapy (RapidArc) on patients with brain metastasis to simultaneously treat the entire brain with a concomitant focal boost to grossly identified lesions on MRI scan to try to improve local control and reduce neurocognitive toxicities.

This previous version of this study was a phase I dose escalation trial giving 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease. Prior to this, patients were enrolled onto one of two cohorts with whole brain dose of 30 Gy in 10 fractions with SIB to total of 45 Gy in 10 fractions to gross brain metastatic disease or whole brain dose of 37.5 Gy in 15 fractions with SIB to total of 52.5 Gy in 15 fractions to gross brain metastatic disease. A total of 12 patients have been previously enrolled on this trial. No patients have experienced a dose limiting toxicity (grade 3 or above) at least possibly due to study therapy. Also, no patients experienced local brain failure/progression at a site of treated metastatic brain disease. Based on this, we no longer feel that dose escalation to the gross brain disease is warranted and would proceed with a single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.

Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc

Whole Brain Radiation Therapy With Simultaneous Boost to Gross Metastatic Tumor Volume Using Volumetric Modulated Arc Therapy (RapidArc)

The cumulative incidences of recurrence locally and in the whole brain were reported at the patient level.

Defined as period of time from study entry to to death from any cause or brain tumor recurrence or progression.

Defined time from study entry to death from any cause.

Neurological test score were assessed using the Hopkins Verbal Learning Test-Revised (HVLT).

In the HVLT 12 words are read and the participant is asked to recall them, this is completed 3 times.

Total words recalled are summed to give a score for Total Recall (0-36, higher scores demonstrated better recall).

Delayed recall is conducted 20-25 minutes later on the same list of 12 words (scored 0-12 with higher scores demonstrating better recall).

Retention is calculated as the percent of words recalled (scored 0-100, higher scores representing better recall).

Recognition Discrimination is tested by a series of yes/no responses from the participant identifying 12 target words from a list of 24 and calculated by the number of true positives minus the number of true negatives with higher scores indicating a better outcome.

The Functional Assessment of Cancer Therapy-Brain (FACT-Br) were summed to create the FACT brain trial outcome index (FACT-BR TOI), FACT general (FACT-G), and FACT brain total (FACT-BR Total).

Three FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient.

FACT BR TOTAL (FACT-G + BrCS, possible range 0 - 200) FACT-BR TOI (Trial Outcome Index = Physical Well Being _ Functional Well Being +BrCS, possible range 0 - 148) FACT-G (Fact General, possible range 0 - 108)

Emory University

MD, Principal Investigator

Single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.

Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.

Volumetric Modulated Arc Therapy

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Hui-Kuo Shu

1-year Local Control

Lesion Level Control

1-year Regional Control

Intracranial Control

Distant Intracranial Recurrence

Feasibility by our criteria was met for all participants.

Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients

Brain Progression-free Survival

The 2-year neurocognitive effect was not collected. We collected and reported neurocognitive data up to 6 months after treatment.

Overall Survival

Total Recall

Delayed Recall

Retention

Recognition Discrimination

Neurocognitive Effects

FACT-BR Total

FACT-BR TOI

FACT-G

Quality of Life as Measured by the FACT-Br Subscales

Overall Study

During Stage 1: Optimise nodal treatment margin, Combined real-time use of 'Multi-Leaf Collimator Adaptation' and 'kV Intrafraction Monitoring' will be used to reshape the radiation beam in real-time. The nodal target position stability will be evaluated by the cone beam computed tomography (CBCT) imaging before and after each treatment session for the first 10 patients.

During Stage 2: Use treatment margin, Combined real-time use of 'Multi-Leaf Collimator Adaptation' and 'kV Intrafraction Monitoring' will be used to reshape the radiation beam in real-time. At the same time, multi-leaf collimator (MLC) tracking will be used to reshape the radiation beam in real-time using the margin size determined in Stage 1.

This intervention uses the simultaneous combined use of two technologies: 'Multi-Leaf Collimator Adaptation' and 'kV Intrafraction Monitoring'. kV Intrafraction Monitoring (KIM) measures the motion of tissues targeted for radiotherapy in real time using kV imaging.The multi-leaf collimator (MLC) reshapes the radiation beam to maximise dose to the target tissue and minimise dose to the surrounding healthy tissue. Combining KIM and MLC allows the shaped radiation beam to follow the moving target (the prostate) while remaining fixed on a stationary target (lymph nodes) that are also being treated at the same time.

Combined real-time use of 'Multi-Leaf Collimator Adaptation' and 'kV Intrafraction Monitoring'

Thomas Eade, MBBS, RANZCR

Assessing the feasibility of implementing real-time multi-leaf collimator (MLC) tracking to account for the relative motion of the moving prostate tumour target and the static pelvic nodal target for high-risk prostate cancer patients. The capability of tracking for the relative motion of multiple targets will ensure that all the treatment targets receive correct dose as prescribed by the doctor and minimise side effects to the critical organs.

This study will assess the feasibility of implementing real-time multi-leaf collimator (MLC) tracking to account for the relative motion of the moving prostate tumour target and the static pelvic nodal target for high-risk prostate cancer patients. The capability of tracking for the relative motion of multiple targets will ensure that all the treatment targets receive correct dose as prescribed by the doctor and minimising side effects to the critical organs.

During radiation treatment, the prostate position will be monitored in real time using the KIM technology. The nodal target will be imaged before and after each treatment to evaluate the nodal treatment margin. The MLC tracking is implemented by recalculating the radiation beam shape fit for the moved prostate and static nodal targets and sending the adjusted MLC leaf positions to the treatment delivery system. The actually delivered dose to the patient will be calculated after the treatment and compared to the dose without MLC tracking to assess the treatment efficacy.

All patients receive the intervention for comparison against retrospective matched cohort.

Multi-target Tracking in Prostate Radiotherapy Using MLC and KIM

Phase I Feasibility Study of Accounting for Relative Motion of Multiple Targets in Prostate Cancer Radiotherapy Using Realtime Multi-leaf Collimator Adaptation and Kilovoltage (kV) Intrafraction Monitoring

Share for research purposes with interested parties.

The percentage of fractions delivered without software or mechanical failure

The geometric accuracy of the beam shape, determined by comparing the ideal beam shape with the actual beam shape.

Prostate motion trajectory measured by KIM.

The estimated dose distributions will be compared to the original plan using the dose reconstruction method18 based on the prostate motion trajectory and the logged MLC positions (beam shapes).

Royal North Shore Hospital

Head of Research

Rare Diseases

Acute Graft Versus Host Disease

patients with gynecological cancer treated with adjuvant conventional radiotherapy

Patients with gynecological cancer treated with adjuvant VMAT radiotherapy

VMAT therapy focuses on reducing the dose radiation in adjacent organs at risk

conventional radiotherapy

This is a randomized, controlled, open-label, prospective and longitudinal clinical trial. Rectal, intestinal and bladder EBRT-related toxicity will be assessed according to RTOG / EORTC scales at the first day of EBRT, during the 2nd, 3rd and 4th week of treatment, and 1, 3 and 6 months after the end of radiation treatment. The assessment of quality of life (QoL) will be measured by completing the questionnaire of the European Organization for Research and the Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) version 3.0, in addition to specific QoL questionnaires for cervical and endometrial cancer respectively (EORTC QLQ-CX 24 and EORTC QLQ-EN24), previously validated in Mexican Spanish-speaking population, and which will be simultaneously applied with the RTOG / EORTC toxicity scales.

EXPECTED RESULTS AND PERSPECTIVES:

This trial aims to provide information about the feasibility of using a newer EBRT technique, as effective as conventional 3D-conformal radiation therapy (3D-CRT), but with less toxicity.

BACKGROUND:

The standard of care in gynecological malignancies with high-risk features of recurrence following surgery is adjuvant external beam radiation therapy (EBRT) in the pelvic region, with or without concurrent chemotherapy (CT). This treatment modality offers higher local control and improves overall survival. EBRT has been associated with secondary effects due to toxicity such as cystitis, enteritis and proctitis which can compromise its effectiveness, patient´s quality of life and the interruption of the treatment. Newer EBRT techniques reduce the radiation dosis in normal tissues, with less toxicity. So far, there are no records of radiation-induced toxic effects in our population. The aim of this study is to evaluate the acute toxicity associated with pelvic postoperative EBRT using conventional or VMAT (RapidArc) technique in patients with gynecological cancer.

METHODOLOGY:

This is a randomized, controlled, open-label, prospective and longitudinal clinical trial. Rectal, intestinal and bladder EBRT-related toxicity will be assessed according to RTOG / EORTC scales at the first day of EBRT, during the 2nd, 3rd and 4th week of treatment, and 1, 3 and 6 months after the end of radiation treatment. The assessment of quality of life (QoL) will be measured by completing the questionnaire of the European Organization for Research and the Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) version 3.0, in addition to specific QoL questionnaires for cervical and endometrial cancer respectively (EORTC QLQ-CX 24 and EORTC QLQ-EN24), previously validated in Mexican Spanish-speaking population, and which will be simultaneously applied with the RTOG / EORTC toxicity scales.

EXPECTED RESULTS AND PERSPECTIVES:

This trial aims to provide information about the feasibility of using a newer EBRT technique, as effective as conventional 3D-conformal radiation therapy (3D-CRT), but with less toxicity.

patients with gynecological cancer with an indication of adjuvant radiotherapy after surgical treatment.

A Trial Comparing Acute Toxicity in Patients With Gynecological Cancer Treated With VMAT

A Randomized Open-label Trial Comparing Acute Toxicity in Patients With Gynecological Cancer Treated With Adjuvant Conventional Versus VMAT Radiotherapy.

The acute toxicity will be measured, with RTOG acute radiation morbidity scoring criteria scale, this has four grades from 0 to 4, and higher values represent a worse outcome. The principal symptoms to evaluate are genitourinary and lower gastrointestinal.

measured by completing the questionnaire of the European Organization for Research and the Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) version 3.0, previously validated in Mexican Spanish-speaking population.

The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items..

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hypofractionated Radiation Therapy in Prostate Cancer	NCT01764646	Malignant Neopl... Local Disease	Intensity modul... Volumetric modu... Image guided ra...	18 Years - 85 Years	University Hospital, Geneva
Hypofractionated Radiation Therapy in Prostate Cancer	NCT01764646	Malignant Neopl... Local Disease	Intensity modul... Volumetric modu... Image guided ra...	18 Years - 85 Years	University Hospital, Geneva
Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc	NCT01218542	Neoplasm Metast...	Volumetric modu...	18 Years -	Emory University
Multi-target Tracking in Prostate Radiotherapy Using MLC and KIM	NCT02588846	Prostate Cancer	Combined real-t...	18 Years -	Royal North Shore Hospital
A Trial Comparing Acute Toxicity in Patients With Gynecological Cancer Treated With VMAT	NCT03899376	Gynecologic Can...	Volumetric modu... conventional ra...	18 Years - 80 Years	National Institute of Cancerología

Spots Global Cancer Trial Database for volumetric modulated arc therapy