Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Men of any ethnicity with a family history of prostate cancer defined as:

* Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years
* Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at \<70 years
* Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age

Men of black African or black African-Caribbean ancestry defined as:

Both parents and all 4 grandparents being of black African or black African-Caribbean ancestry.

Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (gene mutation including BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol); and/or being known to have a high polygenic risk score (PRS) (defined as being in the top tenth percentile prior to enrolment).

All men will be offered a MRI and prostate biopsy and they can either opt to undergo these procedures at baseline irrespective of PSA level at baseline or they can undergo PSA-only screening until clinically indicated based on an age-defined PSA threshold, at which point, they will undergo prostate MRI and biopsy once their PSA reaches the threshold.

Prostate MRI and Biopsy

Elizabeth K Bancroft, PhD

Eva McGrowder, PhD

Rosalind A Eeles, FRCP FRFR

Rosalind A Eeles, FRCP FRCR

Rosalind A Eeles

Prostate cancer is now the most common cancer in men in the Western world. In the United Kingdom (UK), there were over 52,000 new cases diagnosed in 2016-2018 and a lifetime risk of 1 in 8. Prostate cancer (PrCa) can run in some families and research studies have identified several genetic changes in Caucasian populations that are thought to increase the risk of developing prostate cancer. Other studies have shown that men from certain ethnic groups also have a higher risk of prostate cancer, and this includes men of black African or black African-Caribbean ancestry. This study aims to look at men with a higher risk of prostate cancer based on their ethnicity, family history and/or genetic predisposition to see whether any of these genetic changes are present in their DNA (genetic material) and whether this could be a helpful screening tool in prostate cancer screening programmes. It is thought that many genetic changes are involved in the development of prostate cancer and research is being carried out worldwide to identify these genetic changes. Some of these changes may cause a very slight increase in prostate cancer risk while others may cause a much larger increase in risk of developing prostate cancer. The investigators will invite (i) men of any ethnicity with a family history of prostate cancer; (ii) men of black African or black African-Caribbean ancestry; and (iii) men of any ethnicity with a known genetic predisposition to having prostate cancer (e.g., being known to have inherited a gene mutation that increases risk of prostate and/or being known to be in the top tenth percentile of the polygenic risk score (high PRS score prior to enrolment) for targeted prostate screening (Prostate Specific Antigen (PSA) testing, MRI and a biopsy of the prostate gland) and genetic profiling. The outcome of these prostate cancer screening investigations will be compared with the genetic profiles of those taking part in the study in order to look for certain genetic changes in the gene code that are thought to increase prostate cancer risk. This research will help us to determine what the role of such genetic profiling is in a prostate cancer screening programme and if it helps identify men at high prostate cancer risk.

Purpose and Design

The aim of the PROFILE study is to investigate the role of targeted prostate cancer screening in men at a genetically higher risk to estimate the incidence of PrCa and the sensitivity and specificity of PSA screening in these populations and correlate this with genetic profiles and biological endpoints. Additionally, the study aims to identify biomarkers from biological samples (such as blood and urine) as well as imaging technologies (e.g. MRI and new imaging techniques) as predictive markers of the risk of developing PrCa and to correlate these with genetic risk. This study has been designed using an observational approach to look at the correlation of cancer incidence (on biopsy) with genetic profile. The aim is to evaluate targeted screening for prostate cancer in men at a genetically higher risk to estimate the incidence of prostate cancer and the sensitivity and specificity of PSA screening in these populations and correlate this with genetic profiles (i.e. single nucleotide polymorphism (SNP) profiles) and biological endpoints.

Three cohorts will be recruited:

1. Men of any ethnicity with family history of prostate cancer.
2. Men of black African or black African-Caribbean ancestry.
3. Men of any ethnicity with a genetic predisposition to having prostate cancer (e.g., being known to have inherited a gene mutation that increases risk of prostate cancer (i.e. high-risk gene mutation) and/or being known to have a high polygenic risk score (high PRS score) defined as being in the top tenth percentile prior to enrolment.

Men with no prior screening will be offered biopsy and genetic profiling. This will provide data on genetic profiling and correlation with biopsy irrespective of PSA in men who have not had any previous screening.

A PSA screening algorithm was considered as an alternative to biopsy but there is great controversy over the PSA threshold that should be used as a cut-off. Recent data have shown that a considerable percentage of men with a PSA within normal range have cancer at biopsy. Therefore, it was decided by the Steering Committee that all participants should be offered a biopsy within this study. This will tell us the acceptability of this approach.

Some men may opt not to have biopsy at baseline (i.e. initial stage). These men will be followed up with annual PSA, whereby prostate biopsy would be offered if PSA is above or equal to 1.0ng/ml if the man is aged under 50 years, or where PSA is above or equal to 2.0ng/ml if the man is aged fifty years or over.

Eligibility and Recruitment

Either:

(1) Men of any ethnicity with a positive family history of PrCa defined as:

* Men with a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years
* Men with two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at \<70 years
* Men with three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age

Or (2) Men of black African or black African-Caribbean ancestry defined as:

Both parents and all 4 grandparents being either black African or black African-Caribbean.

Or (3) Men of any ethnicity with a genetic predisposition to having prostate cancer e.g., being found to have inherited a gene mutation that increases risk of prostate cancer (e.g. BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in the study protocol); and/or being known to have a high polygenic risk score (PRS) (defined as being in the top tenth percentile prior to enrolment).

* Age 40- 69 years
* WHO performance status 0-2
* Absence of any psychological, familial, sociological or geographical situation potentially hampering compliance with the study protocol and follow up schedule.

Exclusion criteria

* Previous cancer with a life expectancy of less than five years.
* Previous PrCa
* Negative biopsy within one year before recruitment
* Comorbidities making prostate biopsy risk unacceptable (anticoagulants or antiplatelet medication including Warfarin, Clopidogrel, Apixaban, Dabigatran or other NOAC (Novel Oral Anti-Coagulant); poorly controlled diabetes, cardiovascular/respiratory disease, immunosuppressive medication or splenectomy).
* Men with body mass index (BMI) 40 and above.
* Men with BMI 35 and above plus other co-morbidities.
* Contraindications to having an MRI (non-MRI compliant pacemakers, aneurysm clips, metallic cardiac valve/stent, Ventriculo-Peritoneal (VP) shunt, cochlear implant, neurotransmitter, metallic foreign bodies in eye(s), other metalwork, claustrophobia)
* Any significant psychological conditions that may be worsened or exacerbated by participation in the study

Subject Withdrawal

o Subjects may withdraw from the study at any time if they so wish without giving a reason. No further data will be collected about that individual, and any unused samples will be destroyed. Data collected up to that point will be retained for audit purposes.

Cancer cases Men who are found to have prostate cancer at biopsy will be referred to their local urologist for treatment according to local policy. Men will be followed up for 10 years in order to evaluate the different treatment regimens.

Genetic Profiling All men will have genetic profiling to correlate with disease status and men will be given the results of this test. It will be emphasised that these are research results and written information will be provided as a reference guide.

Informed Consent All subjects will be informed of the aims of the study, the possible adverse events, the procedures and possible hazards to which he will be exposed, and the mechanism of treatment allocation if prostate cancer was to be diagnosed. He will be informed as to the strict confidentiality of his patient data, but that his medical records may be reviewed for trial purposes by authorised individuals other than their treating physician.

It will be emphasised that participation in this study is voluntary and that the subject is allowed to refuse further participation in the protocol whenever he wants. This will not prejudice the subject's subsequent care. Documented informed consent will be obtained, according to the principals of good clinical practice (GCP), for all subjects included in the study before they are registered onto the study.

Risks, burdens, benefits There is a risk of complications from having a prostate biopsy, and these complications are detailed in the patient information sheet, together with likelihood of incidence. Complications are rare and standard procedures will be followed at all sites to minimise their occurrence. The benefit of taking part may be that prostate cancer may be diagnosed in men previously unaware that they had the disease. While there is the potential for overdiagnosis of indolent disease, there is also the potential for detecting and treating clinically significant disease.

Provision of results from the genetic profiling One further consideration is the occurrence of anxiety as a result of taking part in the study, particularly in receiving research genetic test results. There is considerable uncertainty about how genetic profile relates to predicted risk of prostate cancer. For this reason individualised written information will be provided to each participant putting the research results in the context of the current population risks. It will be stressed that these are research results only and that the investigators do not fully understand the meaning of the results.

A psychosocial study is being run concurrently and will explore these issues in more depth and the participant's experience of receiving these results will be an important component of the evaluation of this study.

Confidentiality All information which is collected will be accessible only to the immediate study team. Any data that is shared will be de-identified and any published data will be anonymised so that no participant is recognisable from the results.

Medical records and the data collected for the study may be looked at by authorised persons from the Institute of Cancer Research, by regulatory authorities and by authorised people to check that the study is being carried out correctly. All will have a duty of confidentiality to participants.

End of Study Follow-up After the participant has completed the study they will be advised about any ongoing screening or follow-up that is required. This will be organised through the participants general practitioner (GP).

Use of samples in future research The informed consent process will explain that samples are donated as a "gift". If any of the samples collected are to be considered for use in future research projects this would have to be approved by the Ethics Committee first.

The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment

Anonymised data can be applied for via the Data Access Committee

To investigate the role of targeted prostate cancer screening in men at higher genetic risk (i.e. family history, ethnicity, gene mutation status), its association with specific genetic profiles and biomarkers as predictive tools of the risk of developing prostate cancer and to correlate these with genetic risk.

To determine the incidence and aggressiveness of prostate cancer in these men at a higher genetic risk.

To determine whether imaging techniques such MRI can be used to identify prostate cancer when compared to prostate biopsy results.

To determine the incidence of abnormal imaging at MRI in correlation with biopsy outcome.

To identify biomarkers from biological samples and determine their association with prostate biopsy result.

To identify imaging biomarkers and determine their association with prostate biopsy result.

Royal Marsden NHS Foundation Trust

University of Cambridge

University of Oxford

Queen Mary University of London

Institute of Cancer Research, United Kingdom

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

Fluorouracil

Cisplatin

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.

Induction chemotherapy (21 day cycle)

* Drug: cisplatin 80mg/m2 (day 1)
* Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion)

olaparib plus chemoradiotherapy (8 weeks)

* Drug: olaparib
* Drug: Cisplatin
* Radiation

Given twice daily. Exposure will escalate by daily dose and duration.

olaparib

cisplatin

Total dose will be 70Gy in 35 fractions over 7 weeks.

Intensity Modulated Radiotherapy

Martin D Forster, MBBS

The aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. The dose decided on in this part of the study will become the recommended dose for the randomised Phase II trial.

This is a dose escalating Phase I/II trial evaluating the safety and tolerability of the addition of olaparib to CRT in high risk locally advanced human papillomavirus (HPV) negative Squamous Cell Carcinoma of the Head and Neck (HNSCC). A fixed dose of weekly cisplatin and intensity-modulated radiation therapy (IMRT) will be used, with doses of olaparib escalating for consecutive days and both dose level and duration will be increased through each cohort.

This Phase I trial will assess how olaparib, a poly ADP ribose polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy treatment.

Patients will be recruited from sites in the UK only.

A placebo controlled, randomised Phase II trial will follow once the recommended dose and schedule of olaparib has been established.

Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

A Phase I/II Study of Olaparib in Addition to Cisplatin Based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)

AstraZeneca

University College, London

Symptoms and General Pathology

Behaviors and Mental Disorders

Nervous System Diseases

Syndrome

Depression

Depressive Disorder

Fatigue

Parasomnias

Pain

Caregiver Burden

Behavioral Symptoms

Not hospitalized cancer patients under active treatment

Tone Rustøen, PhD

The complexity of cancer patients' symptoms and health problems constitutes considerable distress and burden for patients and their family caregivers. To help them manage the illness effectively, there is a need to better understand the complexity of symptoms and symptom clusters in patients and caregivers. Therefore, the purpose of this research is to explore a set of important fundamental research questions to advance the scientific knowledge of cancer patients' and caregivers' symptoms, symptom clusters and health-related quality of life. The investigators will follow 500 cancer patients and their caregivers with repeated measures over 6 months to assess their symptoms, symptom clusters, and quality of life over time. Caregiver burden will also be examined in the caregivers.

The specific aims of the study, where we will follow 500 cancer patients and their caregivers with repeated measures over 6 months, are to:

1. Explore cancer patients' symptoms, symptom clusters and symptom changes over time; and identify subgroups of patients with different symptom clusters.
2. Identify genomic markers for the different patient subgroups.
3. Explore symptoms, symptom clusters and burden in caregivers of cancer patients.
4. Explore relationships between patients' and caregivers' symptoms, symptom clusters, quality of life and caregiver burden.

Patients will be asked to complete questionnaires to collect demographic characteristics and self-reported medical history information, a general symptom inventory, specific measures of the symptoms of pain, sleep disturbance, fatigue, depression, functional status and quality of life. The patients' medical record will be reviewed for disease and treatment information.

The caregivers will also be asked to complete questionnaires about a general symptom inventory, specific measures of the symptoms of pain, sleep disturbance, fatigue, depression, functional status, quality of life and caregiver burden.

Data Analyses will be done to identify symptom clusters of the different symptoms, and to identify patient subgroups based on their symptom experience and quality of life. Variations in symptom clusters and quality of life over time will also be evaluated. Genetic analyses will also be done in the patients.

DNA analyses for genotyping subgroups of patients based on their experience with pain, fatigue, sleep disturbance and depression will test the hypothesis that gene polymorphisms within the selected candidate genes will exhibit significant differences in frequency distribution among the different patient subgroups that are identified through cluster analysis.

Symptom Clusters in Cancer Patients and Their Caregivers- a Longitudinal Study

Advancing the Science of Symptom Management and Support for Cancer Patients and Their Caregivers

University of California, San Francisco

Oslo University Hospital

Professor

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cardiotoxicity

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Bassam Abdulkarim, MD

Radiotherapy is standard treatment for breast cancer after lumpectomy. Although this treatment showed substantial patient benefits and decrease of local recurrence and deaths from breast cancer, it also results in some severe late side-effects, such as skin fibrosis and cardiac failure. It's possible to offer breast irradiation (RT) and minimizing toxicities radiation dose to skin, lung and heart. This will be achieved with highly conformal RT delivery using Tomotherapy. We plan to evaluate this approach in clinical study. We plan also to evaluate the value of genomic, cellular and functional imaging endpoints as predictive markers of toxicity in our breast cancer population. This program is expected to prospectively validate that Tomotherapy for breast RT can decrease skin, lung and heart toxicities and maintaining excellent cancer control after lumpectomy.

Radiotherapy is standard treatment after conservative surgery for early-stage breast cancer. Although this approach substantially improves local control and reduces deaths from breast cancer, it also results in some severe late side-effects, including skin fibrosis, deaths from radiation-induced cardiac disease and lung cancer. We will undertake a novel approach to the evaluation of radiation-induced toxicity during and after whole breast irradiation (RT) following breast-conserving surgery, with the long-term strategic goal of minimizing RT toxicity in early breast cancer. Theoretically, it is possible to achieve this goal through very highly conformal RT delivery and avoidance of RT in toxicity-prone individuals where possible. We plan to evaluate the utility of genomic analysis, cellular DNA repair competence, and functional imaging endpoints as predictive markers of toxicity in our breast cancer population. This program is expected to (a) prospectively validate that HT for breast RT can decrease acute toxicity whilst maintaining excellent cancer control after BCS; (b) demonstrate that novel surrogate markers will aid in the prediction of acute and/or late normal tissue toxicity with a view to identify toxicity-prone (or conversely, robust) individuals from amongst the breast cancer population.

Novel Surrogate Markers as Predictors of Radiation Toxicity in Breast Cancer Patients Undergoing Helical Tomotherapy Compared to Standard Radiation Therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment	NCT02543905	Prostate Cancer Prostate Biopsy Genetic Counsel... Genetic Markers	Prostate MRI an...	40 Years - 69 Years	Institute of Cancer Research, United Kingdom
Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck	NCT01491139	Carcinoma, Squa...	olaparib cisplatin Intensity Modul...	18 Years -	University College, London
The PROFILE Study: Germline Genetic Profiling: Correlation With Targeted Prostate Cancer Screening and Treatment	NCT02543905	Prostate Cancer Prostate Biopsy Genetic Counsel... Genetic Markers	Prostate MRI an...	40 Years - 69 Years	Institute of Cancer Research, United Kingdom
Symptom Clusters in Cancer Patients and Their Caregivers- a Longitudinal Study	NCT00769301	Cancer Pain Fatigue Depression Sleeping Proble...		18 Years -	Oslo University Hospital
Symptom Clusters in Cancer Patients and Their Caregivers- a Longitudinal Study	NCT00769301	Cancer Pain Fatigue Depression Sleeping Proble...		18 Years -	Oslo University Hospital
Novel Surrogate Markers as Predictors of Radiation Toxicity in Breast Cancer Patients Undergoing Helical Tomotherapy Compared to Standard Radiation Therapy	NCT00563407	Genetic Markers Cardiac Toxicit... Breast and Skin...		18 Years -	AHS Cancer Control Alberta
Symptom Clusters in Cancer Patients and Their Caregivers- a Longitudinal Study	NCT00769301	Cancer Pain Fatigue Depression Sleeping Proble...		18 Years -	Oslo University Hospital
Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck	NCT01491139	Carcinoma, Squa...	olaparib cisplatin Intensity Modul...	18 Years -	University College, London

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