Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Adenocarcinoma

Prostatic Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hashim Ahmed

The proposal will explore a trial design called the cohort-multiple RCT (cmRCT) or as it has been recently coined, the Trials WithIn Cohorts (TWICS) design. This design has been used in a number of disease areas, both benign and cancer. Prostate conditions have been chosen since they are extremely common and if malignancy occurs the majority of men with the disease are regarded as living with a chronic condition due to its long natural history and in which innovative approaches, interventions, treatments or changes in management might have a significant patient benefit and impact on the NHS. It therefore fits the cmRCT design very well. Nonetheless, the lessons learned in this study will be of relevance to other disease spaces.

The TWICS or cmRCT design is currently being used in elderly patients, risk of falls, depression, hip fracture, Yorkshire Health Study, scleroderma, breast cancer, colorectal cancer, bladder cancer and kidney cancer, to name a few. In total, a recent systematic review showed that there were 18 ongoing cmRCT studies with 6 in the UK.

The acceptability and feasibility of the cmRCT in the prostate pathway will be tested. This is the first time this method will be tested and therefore piloted. In the first part of the study, the following will be evaluated. What is the accrual rate? What do patients and their healthcare professionals think of the cmRCT design? Is the data collected robust? What are the resource requirements of such a study?A number of novel interventions or changes in the pathway will then be tested and compared to standard care in the cohort that was recruited.

TRIAL AIMS

The pilot phase of PROSPECT is interested in investigating the a) acceptability and feasibility of establishing the cohort of men, i.e. putting the questions of Point of Consent One to men being referred for investigation of prostate cancer, and b) observing the cohort over the study period and collecting data on the participants pertaining to their disease, their treatment and their health status.

A) Acceptability

AIM 1.1: To determine what proportion of men with a clinical suspicion for prostate cancer will participate in an cmRCT.

OBJECTIVE 1.1a: To evaluate proportion of patients approached who agree to participate in the longitudinal cohort. This will be done by calculating the participation rates from men approached for invitation to PROSPECT.

AIM 1.2: To explore barriers and facilitators to implementation of a cmRCT in order to improve and inform patient and/or physician trial information, study processes, interventions, and recruitment and retention of patients. This will be carried out by qualitative assessments in the following areas.

OBJECTIVE 1.2a: To investigate by interview the patient experiences and perspectives on;

* Trial participation,
* The point at which men are approached by the research team to enter the cohort,
* Barriers and facilitators to consent to participate in the cohort,
* Barriers and facilitators to consent to future random selection to undergo a new healthcare intervention,
* Acceptability of monitoring of health status and the tools used to do this in the cohort.

OBJECTIVE 1.2b: To investigate by interview the experiences and perspectives of healthcare professionals (doctors, nurses and admin staff) on;

* Trial design and information to patients and healthcare professionals,
* Feasibility of future random invitation of participants to interventions,
* Tools used for measuring health status.

B) FEASIBILITY

AIM 2.1: To determine the feasibility of recruitment and logistical implementation of PROSPECT in different data collecting centres based in different institutions. This will be broken down into the following sub-questions;

OBJECTIVE 2.1a: Evaluating how the patients are successfully identified and the option of how inclusion in the trial is presented to them.

OBJECTIVE 2.1b: Evaluate patient questionnaire response rates for pre-treatment quality of life.

OBJECTIVE 2.1c: Evaluate patient questionnaire response rates at pre-determined intervals following on from the point of recruitment into the trial to determine how to promote optimal patient response rate and improve data collection.

OBJECTIVE 2.1d: To evaluate completeness and fidelity of clinical data on the men who participate in the cohort.

STUDY DESIGN

Design

The key features of a cmRCT are;

1. Explicitly consented recruitment of a large cohort of patients with the condition of interest.
2. Regular measurement of relevant outcome measures for the whole cohort prospectively in the long-term.
3. Facility to re-approach cohort participants, who are randomly selected from eligible patients within the cohort, inviting them to undergo intervention of interest to researchers with eligible patients not randomly selected entering the control standard care group (see study flowchart 3.3 / 3.4).
4. "Patient-centred" informed consent. The consent process aims to replicate that used in the routine health care setting. Once the patient has been randomly selected for a randomised novel intervention from the eligible patients within the cohort, the second consent process should include detailed and specific information pertaining to the particular intervention or change in management they are being invited to undergo for comparison. Such information will be written and advised using patient representatives and undergo review following submission to REC.
5. Comparison of the outcomes in the randomly selected patients with the outcomes in eligible patients not randomly selected.
6. Capacity for multiple randomised controlled trials over time within the cohort simultaneously.

CONSENT

For men who are participating in the cmRCT there are two points of consent:

POINT OF CONSENT ONE

At Point of Consent One men who are referred for investigation of prostate cancer will be asked two questions. The first question relates to whether they are willing to join the cohort and have data collected directly from them over time on a regular basis. This data will include health-related quality-of-life data (at recruitment, 0-6, 6, 12, 18 \& 24 months post recruitment), linkage to their medical records so that researchers can know what happens to them over time, and access to other data about them held on national health registry databases. Also, at point of consent one, prospective participants will be asked (second question) whether they agree to being randomly selected in the future to interventions or changes in management in order to compare to standard care. It will be explained that this second invitation will be on a random basis. In other words, everyone eligible within the cohort will have the same chance of being randomly selected. The patient would still have the option of saying 'no' after the random selection when they are approached.

POINT OF CONSENT TWO

The second point of consent is the invitation to undergo an intervention or change in management that the research team wishes to compare to standard care. Participants will have already agreed to the possibility of being invited to undergo intervention at Point of Consent One (i.e. enrolment into the cmRCT). The participant will have been randomly selected from amongst all the eligible men for the given intervention from within the large cmRCT cohort prior to being approached by the trial team. Then, the trial team will approach the participant and invite him to undergo the intervention. This will entail a comprehensive consent process that pertains directly to the intervention being proposed in a patient-centred manner. The participant can agree or refuse to undergo the intervention. If he does not wish to undergo the treatment he will continue under follow-up in PROSPECT.

Participants undergoing intervention will continue to have follow-up in the same manner as men who have not been randomised from within the cohort and thus provide outcome data to form the control arm. Comparison of the outcomes of those men who underwent trial intervention against those who did not will allow us to analyse the effectiveness of the intervention in as robust a manner as possible given that the key feature of randomisation when creating the control vs. the intervention arms has been preserved. As such, the control arm of the cmRCT will be similar to the intervention arm in all features, known and unknown, except the intervention of interest. This will allow for the maintenance of epistemological superiority of the data produced for evaluating new tests or treatments whilst getting to this point in a way that might be more acceptable to patients and therefore more likely to be successful and efficient for researchers.

The second stage of PROSPECT will be to investigate and evaluate in a similarly careful manner the feasibility and acceptability of randomising men from the cohort of eligible men to interventions or changes in management that require evaluation, following submission to REC. As part of the cmRCT design, these men randomly selected are re-approached and invited to consider undergoing the intervention of interest. Patients who are randomly allocated to the control arm will also receive standard of care, and are not informed about their participation in the control arm. This additional consent will be obtained at the time of consent for the cohort study.

STUDY SETTING AND POPULATION

All men referred for investigation of prostate cancer. The inclusion criteria for this cohort is deliberately broad.

PROState Pathway Embedded Comparative Trial

Rate of consent to inclusion to PROSPECT cohort at the original point of contact by the research team. This will be calculated on an ongoing basis and will be reviewed at 6 months and one year from opening and at the end of the study period

To investigate by interview the experiences and perspectives of patients who:

* Consented to inclusion in the cohort study,
* Declined to enter into the cohort,
* Consented to inclusion in the cohort initially but who subsequently requested to leave the cohort,

Structured thematic interviews will be conducted by the researchers who will follow the Interview Questionnaire Template. The interviews will be recorded and transcribed in house before analysis and theme-based extraction of the reasons behind men's decision regarding inclusion in the cohort. Recruitment for qualitative interviews will continue until no further themes emerge.

The opinions of healthcare professionals who regularly look after men with prostate problems will be sought through semi-structured interviews that focus on implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.

Evaluation of the number of men approached to enter PROSPECT against the number of men referred to the participating centres for investigation of prostate cancer.

PROSPECT will conduct a review of the pathway by which they approach men to invite them to the cohort. Part of this will be included in the qualitative interviews with men and healthcare professionals. Particular points of interest will be the timing of consent process, the trial personnel who gain consent, and the number of men who give consent who are subsequently not diagnosed with prostate cancer.

Participants will be given a standard Quality of Life Questionnaire (EQ5D-5L) at the point at which they consent to inclusion into PROSPECT. Data completeness will be calculated at 6 months after opening and on an ongoing basis as long as the study is open.

Participants will be given a standard Quality of Life Questionnaire (EQ5D-5L) at the point at which they consent to inclusion into PROSPECT. Data completeness will be calculated at 12 months after opening and on an ongoing basis as long as the study is open.

All participants will be asked to complete questionnaires on disease specific quality of life at the following points;

* Recruitment to cohort.
* 0-6, 6, 12, 18, 24 months from recruitment to cohort
* Yearly questionnaires thereafter during inclusion in the cohort if trial remains open (i.e., post pilot phase).

PROSPECT will use three self-reporting quality of life validated questionnaires. The responses from the questionnaires will be of value as they will provide an informative vignette of the experience of men after the diagnosis of prostate cancer and they can be compared against the experience of men who are investigated for but not diagnosed with prostate cancer. In terms of evaluating the feasibility of the cmRCT design, PROSPECT will calculate the rates of response from participants with these questionnaires. Questionnaire response rates will also inform PROSPECT of the understanding of the acceptability of the cmRCT design study to patients.

Feasibility of collecting data from the participating centres evidenced by the completeness of data for cohort participants including; i. Subject Data: age, co-morbidities, ECOG/WHO Performance Status, ethnic risk, family risk ii. Disease Characteristics: PSA, MRI (volume, score), biopsy findings (cancer or not, grade if cancer, length of maximum cancer, other pathology), TNM stage if cancer iii. Treatment Data: modality, follow-up, adjuvant and salvage treatments, mortality Analysis will be conducted at one year after opening the PROSPECT and yearly thereafter in order to monitor any trends in improving or faltering data accrual on participants, as long as the study is open.

The integrated qualitative component will explore patients who;

* Consented to inclusion in the cohort study,
* Declined to enter into the cohort,
* Consented to inclusion in the cohort initially but who subsequently requested to leave the cohort

Structured thematic interviews will be conducted by the researchers who will follow the Interview Questionnaire Template. The interviews will be recorded and transcribed in house before analysis and theme-based extraction of the reasons behind men's

The opinions of healthcare professionals who regularly look after men with prostate cancer will be sought through conducting semi-structured interviews that focus on ethics, implementation, practicality and efficiency of PROSPECT. There will be a different Interview Questionnaire Template for interviews with healthcare professionals.

Imperial Clinical Trials Unit (ICTU)

Wellcome Trust

Imperial College London

Head and Neck Neoplasms

The experimental intervention consist of a PEI for 10 weeks. The PEI will be executed 6 to 7 weeks during and 3 to 4 weeks after (C/B)RT.

Patients who were randomized in the PEI group and accepted the invitation to undergo the experimental intervention receive a PEI for 10 weeks. The PEI will be executed 6 to 7 weeks during and 3 to 4 weeks after (C/B)RT. The PEI consists of a 60 minutes intervention twice a week and will be supervised by a physiotherapist specialized in oncology.

Patients who receive the intervention also have to do home-based aerobic and muscle strength exercises by themselves three times a week.

Experimental Intervention

Caroline Speksnijder, Dr.

Jorine Vermaire, Dr.

Yvette Kriellaars, Msc.

The goal of this trial within cohorts study is to determine and compare physical performance, muscle strength, fatigue, quality of life, body composition, nutritional status, physical activity, treatment tolerability of radiotherapy (RT), chemoradiation (CRT) or bioradiation (BRT), and healthcare related costs in patients with head and neck cancer (HNC) with and without a 10 week physical exercise intervention (PEI) during RT, CRT or BRT ((C/B)RT).

Patients who were randomized in the PEI group and accepted the invitation to undergo the experimental intervention receive a PEI twice a week for 10 weeks. The PEI will be executed 6 to 7 weeks during and 3 to 4 weeks after (C/B)RT.

Researchers will compare patients who undergo the PEI with patients who did not undergo the PEI to see if there is difference in physical performance, muscle strength, fatigue, Quality of Life, body composition, nutritional status, physical activity, treatment tolerability of (C/B)RT , and healthcare related costs in patients with Head and Neck Cancer (HNC) with and without a 10 week Physical Exercise Intervention (PEI) during (C/B)RT).

In this study a TwiCs design will be used. The TwiCs design consists of an experimental intervention study within an observational longitudinal cohort. This design uses a staged-informed consent. Patients will be asked to participate in an observational longitudinal cohort study and will be informed about the design with the probability to be randomly invited for an experimental intervention which they can accept or refuse. When patients are willing to participate in the observational longitudinal cohort, an informed consent (IC) will be signed. Directly after cohort enrollment, all patients will be randomized.

Physical Exercise for Patients With Head and Neck Cancer

The Effect of Physical Exercise During Radiotherapy on Physical Functioning in Patients With Head and Neck Cancer: a Trial Within Cohorts, the VITAL Study

Assessed by the EuroQol- five dimensions- five level (EQ-5D-5L). This questionnaire contains 6 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a total score for global health. The first 5 item have 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The score of these item can range from 0 to 4. The higher the total score of these five items, the lower the quality of live. The global health scores on a range 0-100. The higher the score of this item, the higher the global health.

Assessed by the European organisation for research and treatment for cancer quality of life questionnaire (EORTC QLQ-C30). This questionnaire contains 30 questions scoring 9 subscales and 6 single items: 5 functional scales, 3 symptom scales and 1 global health / quality of life scale. The score of each subscale of single items ranges from 0 to 100. A higher score on the functional scales means a high level of functioning. A higher score on the symptom scales means a high level of experiencing symptoms. A higher score on global health / quality of life means a high score of quality of life.

Assessed by the European organisation for research and treatment for cancer quality of life questionnaire head and neck module (EORTC-QLQ-H\&N43). This questionnaire contains 43 specific head and neck cancer questions scoring 19 subscales of symptoms. The higher the score of the subscale, the higher the level symptomology.

Assessed by the multidimensional fatigue inventory (MFI). The MFI contains 20 items scoring the following domains: general, physical and mental fatigue, and reduced activity and motivation. Every scale scores 4 till 20. The greater the score, the more fatigue or limitations in live because of fatigue.

Assessed by the short nutritional assessment questionnaire (SNAQ). The short nutritional assessment questionnaire (SNAQ) consists of three questions and will be used to monitor nutritional status and assess the risk of malnutrition. The total score of this questionnaire ranges from 0 to 7. 0 means no nutritional problems and a high score means malnutrition.

Assessed by the short questionnaire to assess health enhancing physical activity (SQUASH). The SQUASH measures the frequency, duration and intensity of 4 different physical activity: physical activity going to work, physical activity during household activity, physical activity at work, physical activity in spare time. The higher the score, the higher the level of physical activity.

tolerability will be retrieved from medical records and registered as the percentage of scheduled treatment completion, percentage of (C/B)RT adjustment and type of (C/B)RT adjustment.

age, gender, education, employment, marital status tumour site, disease stage, comorbidity, HPV status, tobacco and alcohol use, nutrition status and type of treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PROState Pathway Embedded Comparative Trial	NCT04400656	Prostate Cancer Non-metastatic ... Metastatic Pros... Prostate Adenoc... Metastatic Pros... Prostate Cancer...		18 Years -	Imperial College London
Physical Exercise for Patients With Head and Neck Cancer	NCT05988060	Head and Neck C...	Experimental In...	18 Years -	Institute Verbeeten

Spots Global Cancer Trial Database for twics

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Spots Global Cancer Trial Database for twics

Every month we try and update this database with for twics cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for twics cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.