Cancer studies

There are approximately 16,000 new cases of rectal cancer in the UK per year. Surgery is the mainstay of treatment which is associated with peri-operative mortality and long-term morbidity. Locally advanced disease is treated initially with preoperative radiotherapy, in the main using long-course chemo-radiotherapy (LCCRT) at 45 to 50 Gy, followed by major surgery 8 to 15 weeks later (referred to in this protocol as standard surgical pathway) or selectively by short-course radiotherapy (SCRT) at 25 Gy, traditionally followed by major surgery within 10 days, but based on modern trial results, increasingly major surgery is being delayed for 6 to 8 weeks.

In 10% to 20% of cases, chemo-radiotherapy (CRT) may result in a complete disappearance of the rectal tumour. In patients without residual tumour on imaging and endoscopy (clinical complete response [cCR]), a watch-and-wait (W&W) policy (omission of surgery with follow-up) might be considered as an alternate to major resection. This represents a new paradigm for treating rectal cancer. But there are concerns that this approach is oncologically unsafe outside published series from selected specialised centres.
While randomised trials would represent the ideal way to evaluate the natural history and efficiency of W&W in patients with cCR, there is a general international option that such trials are “unlikely” and that investigators have observed that “many patients ….. express a strong preference not to undergo major surgery”.
Thus, there is a continuing need to prospectively collect clinical data in a standardised manner to monitor the natural history of patients with CCR managed by W&W.

The HER2-RADiCAL study is for patients with HER2-positive breast cancer who:

-started their course of drug treatment (chemotherapy + trastuzumab + pertuzumab) before surgery;
-have had breast surgery;
-and have been found to have the best possible response to treatment (a “pathological complete response” or “pCR”).

A pCR means that there were no remaining living cancer cells in tissue removed at surgery. We already know that such patients have good outcomes with only a small chance of the cancer returning, and so it is possible that the side effects and risks of continuing all of these treatments in combination could outweigh any benefit.

The study will investigate whether a more personalised treatment plan can be offered, with the aim of allowing patients with a pCR to safely receive less drug treatment after surgery. Study participants will not receive a type of chemotherapy called an anthracycline, they will continue treatment with trastuzumab to complete 9 cycles (rather than 18), including the cycles given before surgery. No more pertuzumab or any type of chemotherapy will be given after surgery. Any other treatment that might have been recommended (like hormone therapy or radiotherapy) will be given as normal.

Patients will be asked to donate tissue samples removed during routine biopsy procedures or surgery. No new tissue samples will be taken for research purposes.

The HER2-RADiCAL study aims to recruit around 720 patients with HER2-positive breast cancer and a pCR, to test whether these patients can safely receive less trastuzumab, pertuzumab and chemotherapy after surgery. This reduction of drug treatment may not only benefit the patient, but also save NHS resources.

Data from routine NHS records on all patients with HER2-positive breast cancer in the UK will be collected in addition to the study data to assess the cost-effectiveness of this response-adapted approach.

For more information please contact the Clinical Research Nurse on [email protected].

Female hormones can help some breast cancers to grow. So most women who have had breast cancer are put on endocrine therapy such as tamoxifen which stops oestrogen from helping the cancer to grow.

However in some women the cancer comes back while they are on endocrine therapy. Often we learn too late that the treatment wasn’t working so we need to know much sooner whether it’s effective.

We can tell from mammograms how dense a woman’s breast tissue is. For some women their breasts become less dense while they are on endocrine therapy. We think that might mean that the treatment is working. We think if a woman’s breasts remain dense while on treatment, her cancer may be more likely to come back.

The aim of this study is to prove whether a reduction in breast density really does mean that the endocrine therapy is keeping the cancer away.

We have identified 2500 women who have been recruited into a research project called Mammo50. These women are all over 53 years old, have had a lump removed. 2000 are on endocrine therapy and did not have chemotherapy. We want to transfer their mammograms to a central imaging centre and use a computer and radiologists to assess if the breast tissue has become more or less dense. (We will also look at mammograms from 500 similar women who did not have endocrine therapy as a control group). The progress of these women is then followed so that we will then see if a change in density of the breast tissue is related to the effectiveness of the endocrine therapy.

The ANTHEM Feasibility Study : Is A Novel THErapeutic mammaplasty procedure a safe and effective surgical alternative to Mastectomy for treatment of breast cancer?

Breast conserving surgery (BCS) is the preferred treatment for many women with breast cancer. Standard techniques, however frequently result in poor cosmetic outcomes and mastectomy (removal of the breast) with or without immediate breast reconstruction is often recommended. Currently 40% of the 55,000 women diagnosed with breast cancer each year undergo a mastectomy but of these only 1 in 4 receive reconstruction.

Oncoplastic breast conservation surgery (OPBCS) describes a range of volume replacement (e.g local perforator flap LPF)) and volume displacement techniques (e.g Therapeutic mammaplasty (TM)) that may extend the boundaries of standard BCS and allow some women to avoid mastectomy and potentially improve their quality of life.

There is a need for high-quality research to determine whether OPBCS offers a safe and effective alternative to mastectomy but preliminary work is needed to ensure a future large-scale study is feasible, well-designed and addresses questions important to patients and the NHS.

The feasibility study will have 4 parts
1. A national survey (a nested service evaluation) to understand current national practice of OPBCS
2. A pilot study to explore how many women are suitable for OPBCS as an alternative to mastectomy; choose to undergo the procedure and whether existing patient-reported outcome questionnaires measure outcomes important to patients undergoing different types of surgery accurately and can reliably be used in a future large study.
3. Interviews with patients to explore their views of different surgical options and the adequacy of questionnaires used to assess key patient-reported outcomes
4. Design of the future study

This study will be the first-step providing high-quality evidence to support the use of OPBCS as an alternative to mastectomy. It will promote choice, improving outcomes for patients, many of whom will be long-term breast cancer survivors.

Background: Cancer is a global problem. There is significant pre-clinical and epidemiological evidence demonstrating that aspirin has anti-cancer effects. Recently, individual patient data meta-analyses, from trials designed to assess cardiovascular benefits of aspirin, have shown reductions in cancer incidence and mortality associated with regular aspirin use. Additionally, the CAPP2 trial has demonstrated that daily aspirin prevents cancers associated with the Lynch syndrome.
In the meta-analyses, short-term effects on cancer mortality and a decrease in risk of metastases suggest a role for aspirin in the treatment as well as prevention of cancer. This is supported by several large observational datasets. Concerns over toxicity, particularly serious haemorrhage, have limited the use of aspirin in the primary prevention of cancer. In the adjuvant setting the benefit:risk ratio will be different, with higher morbidity and mortality from recurrent cancer potentially outweighing risks associated with regular aspirin use.

Aim: To assess whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in patients with early stage common solid tumours. International recruitment will allow assessment of the intervention in different communities.

Methods: The question will be addressed in four tumour sites (colorectal, breast, gastrooesophageal, prostate) using parallel trials with a common infrastructure. Each trial will be a multicentre, phase III, double-blind, placebo-controlled randomised trial. Participants will be randomised to 100mg aspirin, 300mg aspirin or a matching placebo, to be taken daily for 5 years.
Primary outcomes will depend on tumour site and trials will be separately powered, requiring 2000-3000 patients with each tumour type to demonstrate effects of aspirin on disease recurrence and survival. Secondary outcomes include overall survival, adherence, gastrointestinal complications and cardiovascular events.

For more information please contact the Clinical Research Nurse on [email protected].

Response to Optimal Selection of neo-adjuvant Chemotherapy in Operable breast cancer: A randomised phase III, stratified biomarker trial of neo­adjuvant 5-Fluorouracil, Epirubicin and Cyclophosphamide vs Docetaxel and Cyclophosphamide chemotherapy.

Neoadjuvant chemotherapy (NAC), for early breast cancer reduces the amount of surgical treatment required, often avoiding the need for mastectomy. A pathological complete response (pCR) is generally associated with excellent prognosis and no pCR is associated with poor outcomes. To maximise pCR patients are treated with both epirubicin and docetaxel containing combinations increasing toxicity due to exposure to both drugs. Retrospective analysis of adjuvant chemotherapy trials strongly suggests that a combination of two genetic markers (CEP17 and TOP2A) predict for epirubicin sensitivity. It may be unnecessary to treat all patients with both epirubicin and docetaxel. Current standard of care in patients with involved axillary nodes before chemotherapy is an axillary dissection. When there is no residual cancer this becomes an unnecessary procedure. The data on the use of sentinel lymph node biopsy post NAC is controversial.

In ROSCO 1056 patients with early breast cancer will be randomised from hospitals around the UK to initial chemotherapy with either epirubicin based or docetaxel based chemotherapy. They will be stratification by CEP17 and TOP2A status. On completion of 4 cycles of chemotherapy patients will undergo surgery and pCR assessment. Where pCR is not achieved patients will receive the alternative chemotherapy as adjuvant treatment. The aim is to determine if CEP17 and TOP2A status can be used to select the appropriate chemotherapy, resulting in higher pCR rates and a requirement for less chemotherapy.

Patients with axillary node involvement prechemotherapy will undergo a post NAC, sentinel node biopsy (SLNB) and axillary clearance as a single procedure to determine if post NAC SLNB is sufficiently accurate to be used as a routine staging tool in this context. Patients will be followed up for 5 years.

For more information please contact the Clinical Research Nurse on [email protected].

ATNEC–Axillary management in T1‐3N1M0 breast cancer patients with FNA or core biopsy proven nodal metastases at presentation who convert to node negative after NEoadjuvant Chemotherapy.

Axillary ultrasound, with fine needle aspiration (FNA) or core biopsy of suspicious lymph nodes, is used in the initial diagnostic work up of breast cancer patients to document nodal status and staging prior to treatment planning. Patients with FNA or core biopsy positive nodes are often referred for neoadjuvant chemotherapy (NACT) and it is currently the standard to perform axillary lymph node dissection (ALND) at the time of breast surgery after completion of NACT. ALND damages lymphatic drainage from the arm, and women may subsequently develop lymphoedema. As well as the discomfort of arm swelling this causes restricted shoulder movement, pain, numbness and other sensory problems. These adverse effects interfere with daily activities, are distressing, impair quality of life and are costly to the NHS in terms of rehabilitative treatments (such as physiotherapy and lymphoedema clinics), as they are often irreversible and symptom relief is difficult. The performance of sentinel node biopsy (SNB) in patients who are node positive before NACT was tested in Z10711and SENTINA2 trials. All patients underwent ALND following SNB. Z1071 showed that the success rate of SNB was 92.5%, 40% of patients had ypN0 disease, and the false‐negative rate (FNR) was 12.6%. The SENTINA study reported 80% success rate of SNB and the FNR was 14%. The FNR decreased when dual mapping agents were used and was less than 10% when ≥3 nodes were removed. Additionally, Z1071 suggested that clip placement at diagnosis of node‐positive disease with removal of the clipped node during SNB reduces the FNR of SNB3. It has been demonstrated that NACT results in eradication of nodal disease in up to 40% of patients. Omission of additional axillary surgery in patients with a negative SNB after NACT appears to be logical however the recurrence and survival rates are unknown and there is a risk of under treatment.

For more information please contact the Clinical Research Nurse on [email protected].

STAMINA - Work Package 4 & 5

The STAMINA programme is a 5 year programme grant for applied research funded by the NIHR. The aim is to determine whether an exercise intervention, embedded in routine NHS cancer care and supported by behaviour change, will confer long-term benefits in cancer-specific quality of life (QoL) and fatigue for men with prostate cancer (PCa) on Androgen Deprivation Therapy (ADT), and be cost effective when compared with optimised usual care. The STAMINA programme has a number of work packages.

*Please note*. This application only pertains to work packages 4/5. All approvals for other work packages i.e. 1-3 have been sought elsewhere.

Work package 4 overview: Building on outputs from preceding work packages as part of the programme grant, and drawing on the MRC framework for complex interventions, Work Package 4 (WP4) will conduct a definitive, pragmatic cluster randomised controlled trial, evaluating the clinical and cost-effectiveness of the STAMINA intervention compared to optimised usual cancer care, in men with prostate cancer, incorporating an internal pilot phase to ensure acceptable recruitment, follow-up and intervention adherence rates.

Work Package 5 overview: A parallel, mixed methods process evaluation will be conducted based on the framework of Linnan and Steckler and informed by the Medical Research Council (MRC) guidance for process evaluation of complex interventions. The acceptability of the intervention is a key aspect for the process evaluation to explore but it is not an explicit element of the Linnan and Steckler framework. We will therefore include an assessment of acceptability following Sekhons framework.

For more information please contact the Clinical Research Nurse on [email protected].

UK Genetic Prostate Cancer Study (formerly the Familial Prostate Cancer Study).

For more information please contact the Clinical Research Nurse on [email protected].

Closed to recruitment – patients in follow up.

Some breast cancers are considered low risk. Low risk means there is a small chance of the breast cancer returning after it has been removed during surgery. Currently, patients with low risk breast cancer have radiotherapy after surgery, followed by drug treatment (hormone therapy tablets) for 5 years. Radiotherapy reduces the risk of cancer returning in the breast (local recurrence). However for patients with a low risk breast cancer, the risk of radiotherapy side effects may start to outweigh its benefit. The PRIMETIME study aims to identify a group of women who can safely avoid radiotherapy because the risk of their cancer returning is so low. A research calculation called IHC4+C will be used to calculate a woman’s risk of cancer returning 10 years after surgery. ‘Very low’ risk patients are those where the chance of their cancer returning 10 years after surgery is less than 5%. This means that out of 100 women with ‘very low’ risk breast cancer, cancer will return in less than five women. In the PRIMETIME study women with ‘very low’ risk breast cancer can avoid having radiotherapy. All other women will be recommended to have radiotherapy according to standard care. Patients who are eligible to take part are those with a small, slow growing breast cancer which has not spread beyond the breast. Patients will be 60 years or over, have had surgery to remove their cancer with a plan to receive at least 5 years of drug treatment (hormone therapy) for their cancer. The study will be conducted in NHS hospitals in the UK. Participating patients will be followed up by their treating hospital for 10 years following surgery.

Closed to recruitment – patients in follow up.

A disease registry study to prospectively observe treatment patterns and outcomes in patients with HER2-Positive unresectable locally advanced or metastatic breast cancer.

Closed to recruitment – patients in follow up.

A randomised clinical trial testing a one week course of curative whole breast radiotherapy against a standard three week schedule in terms of local cancer control and late adverse effects in women with early breast cancer.

Closed to recruitment - patients in follow up.

To Identify A 5-Fraction Schedule Of Curative Radiotherapy Delivered In 1 Week That Is At Least As Effective And Safe As The Current UK Standard 15-Fraction Regimen Delivered Over 3 Weeks Following Primary Surgery For Early Breast Cancer

Closed to recruitment – patients in follow up.

Mammographic surveillance in breast cancer patients aged 50 years and over: a randomised controlled trial.

Closed to recruitment – patients in follow up.

Duration of trastuzumab with chemotherapy in women with early stage breast cancer : six months versus twelve.

Closed to recruitment – patients in follow up.

Trial of Perioperative Endocrine Therapy - Individualising Care.

Closed to recruitment – patients in follow up.

Radiotherapy and Androgen Deprivation in Combination After Local Surgery.

Closed to recruitment – patients in follow up.

Selective use of postmastectomy radiotherapy after mastectomy.

Closed to recruitment – patients in follow up.

AURORA: Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer

Closed to recruitment – patients in follow up.

POSNOC - POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. A randomised controlled trial of axillary treatment in women with early stage breast cancer who have metastases in one or two sentinel nodes.

Closed to recruitment – patients in follow up.

Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy