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.

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.

An IDEAL 2a/2b prospective cohort study to determine the safety and effectiveness of pre-pectoral implant based breast reconstruction

Summary: 55,000 women are diagnosed with breast cancer each year in the UK. 40% undergo mastectomy and of those who choose breast reconstruction, most have an implant-based operation. “Mesh” refers to a biological or plastic material which is used as a scaffold to support a breast implant during reconstruction. Sub-pectoral implant-based reconstruction, placing a breast implant and mesh underneath the chest wall muscle, has become standard despite a lack of evidence to support its use.

A new technique has developed in which a breast implant is completely covered in mesh and placed in-front of the chest-wall muscle rather than underneath. This may result in less pain and more natural results, but this has yet to be established. However, pre-pectoral breast reconstruction (PPBR) is already being performed and is gaining popularity. There is a need to robustly evaluate this technique before it becomes standard.

The Pre-Bra Study is a multi-centre prospective cohort study using mixed qualitative and quantitative methods to determine the safety and effectiveness of PPBR. Female patients aged 16 or over choosing to undergo PPBR for breast cancer or risk reduction are eligible. The study will recruit patients from breast surgery departments in the UK with consultants already performing PPBR. After giving consent, patients will be asked to complete a breast-surgery specific questionnaire (Breast-Q) and rate pain levels. Demographic, clinical, intra-operative, additional treatment and complication data will be collected for the first 3 post-operative months. All patients will be asked to complete the validated BREAST-Q questionnaire at 3 and 18 months. A selected group of surgeons will be interviewed to establish how they began using the novel technique, how they modified it over time and what changes they make when complications occur.

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.

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

Post-operative avoidance of radiotherapy: biomarker selection of women categorised to be in a very low risk group by IHC4+C. 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.

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

The diagnosis of prostate cancer relies on PSA blood tests (which are inaccurate and miss some aggressive tumours) and tissue biopsies (which are expensive and can be painful), meaning there is an urgent unmet clinical need to develop new tests to improve diagnosis. The GlycoScore blood test can detect prostate cancer which is likely to have with superior diagnostic accuracy (with unmatched performance compared to existing tests) and has the potential to transform how prostate cancer is diagnosed and prognosed.

Dr Joy Allen is a co-applicant, leading the Newcastle MIC work packages to:

1) perform optimisation and validation of GlycoScore

2) undertake Care Pathway Analysis and early economic modelling to define the optimal clinical need, patient population(s) and potential role(s) where GlycoScore is most likely to be cost effective.

Care pathway analysis involves qualitative research techniques, which is the focus for this IRAS application.

The focus of the Care Pathway analysis will be to interview healthcare professionals to explore clinical opinion of the use of the GlycoScore test in practice, in both Primary and Secondary Care.

Currently, there is extremely limited information regarding the risks posed by SARS-CoV-2 virus responsible for COVID19 to patients with cancer. This study aims to understand the presentation, management and outcomes of cancer patients with COVID19. The influence of cancer type and treatment will be explored as well as comparing cancer patients with non-cancer patients.
This study will provide valuable information that would educate as well as help inform practice for future possible outbreaks. The information may also inform the development of guidelines with regard to the care and management of cancer patients with viruses such as COVID19 and similar infectious diseases.
Cancer is immunosuppressive, the nature of the immunosuppression seems to be influenced by the microbiota, in addition pulmonary infections are also influenced by the host microbiota, therefore it is important to understand this impact in cancer patients. Analysis of samples from cancer patients with COVID19 offer the opportunity to learn more of these interactions
The purpose of CCP-CANCER UK study is to obtain additional data from patients with cancer who were/are recruited into the Principal CCP-UK study which is the key national protocol for characterising COVID19 in the UK population. This study is designed to supplement, not replace, the Principal CCP-UK protocol.
This study will be open to research sites who are currently participating in the Principal CCP-UK study.
The CCP-Cancer UK study will run for two years. An additional specific cancer data set will be collected from participant’s existing medical records. This cancer specific information when combined with the rich data set related to the COVID-19 episode (derived from CCP-UK) will enable a full understanding of COVID-19 in patients with cancer as well as enable a comparison with non-cancer patients.

Closed to recruitment – patients in follow up.

A randomised trial evaluating the VEGF inhibitor, Bevacizumab (Avastin®), as adjuvant therapy following resection of AJCC stage IIB (T3bN0M0 & T4aN0M0), IIC (T4bN0M0) and III (TxN1-3M0) cutaneous melanoma.

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.

A randomised, multicentre, open-label, phase III trial comparing trastuzumab plus pertuzumab plus taxane following anthracyclines versus trastuzumab emtansine plus pertuzumab following anthracyclines as adjuvant therapy in patients with operable Her2 positive primary 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