A Randomised Trial Of Preoperative Radiotherapy For Stage T3 Adenocarcinoma Of Rectum
Funder
National Health and Medical Research Council
Funding Amount
$521,220.00
Summary
The most appropriate management of locally advanced rectal cancer is controversial as evident by various treatment options available and used. It remains unclear whether pre-operative radiotherapy, and if so what form of therapy, is required for this group of patients. The first aim of this trial is to see whether a long course of radiotherapy with chemotherapy is superior to a short course of radiotherapy. The second aim is to see whether the advantage of pre-operative radiotherapy remains with ....The most appropriate management of locally advanced rectal cancer is controversial as evident by various treatment options available and used. It remains unclear whether pre-operative radiotherapy, and if so what form of therapy, is required for this group of patients. The first aim of this trial is to see whether a long course of radiotherapy with chemotherapy is superior to a short course of radiotherapy. The second aim is to see whether the advantage of pre-operative radiotherapy remains with modern surgical technique. Colorectal cancer is the commonest cancer in Australia and local recurrence leads to severe morbidity with no effective treatment for permanent control. It is important, therefore, to establish treatment regimens that will minimize the risk of local recurrence and it will be significant if this trial can establish that pre-operative radiotherapy can achieve this with minimal toxicity. The quality of life associated with each of the three arms of the trial has not been adequately addressed and will be studied here. The result of this trial will influence designs of future trials if one or other of the pre-operative regimens is shown to be effective. The two regimens, Short Course and Long Course , represent opposing philosophies: minimize the overall treatment time (2 weeks from start of radiotherapy to surgery) to avoid accelerated repopulation versus give more intensive therapy and utilise the sensitising effect from 5-FU on radiotherapy to obtain greater tumour cell kill probability. If one regimen proves more effective than the other, the design of future trials and the way of thinking about the biology will be influenced. There may be implications for the cost of treatment of this disease: Long Course is much about five times more expensive to deliver than Short Ccourse.Read moreRead less
Patient Preferences For Adjuvant Chemotherapy In Early Breast Cancer: What Makes It Worthwhile?
Funder
National Health and Medical Research Council
Funding Amount
$69,420.00
Summary
Adjuvant chemotherapy, used in addition to surgery and radiation, improves recurrence and survival rates in women with early breast cancer. These gains must be balanced against the side effects and inconvenience of chemotherapy including hair loss, nausea, tiredness and risk of infection. This study will determine the gains considered necessary to make modern adjuvant chemotherapy for early breast cancer worthwhile by asking women who have had such treatment. It will determine factors that might ....Adjuvant chemotherapy, used in addition to surgery and radiation, improves recurrence and survival rates in women with early breast cancer. These gains must be balanced against the side effects and inconvenience of chemotherapy including hair loss, nausea, tiredness and risk of infection. This study will determine the gains considered necessary to make modern adjuvant chemotherapy for early breast cancer worthwhile by asking women who have had such treatment. It will determine factors that might influence the gain considered necessary, such as the kind of treatment, the severity of the side effects experienced, social and other factors. Three hundred women who have had modern adjuvant chemotherapy in an ongoing international clinical trial will be recruited and interviewed. The interviews are standardised, scripted and administered by trained researchers to avoid influencing the subjects. Diagrams and props are used to make the questions clearer. Evaluation of these aids is an additional aspect of the project. This information will be invaluable for women and clinicians considering this potentially curative treatment over the next 15 years. The study will also provide new knowledge on how best to provide information about the benefits of treatment. This can then be applied to discussions about treatment in routine clinical practice. The methods are suitable for a wide range of questions in other diseases and settings. The project will be extended to develop the materials for other questions in breast cancer and other settings.Read moreRead less
Optimising Regulatory T Cell Depletion In Combination With Chemotherapy For Enhanced Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$264,816.00
Summary
The drug cyclophosphamide helps the immune system attack cancer by decreasing the number of immune cells that suppress an immune response to cancer ('Regulatory T cells'). This project combines standard chemotherapy with the drug cyclophosphamide in people with mesothelioma and lung cancer. The aim of the project is to find the dose of cyclophosphamide that maximally decreases Regulatory T cells in each patient, and determine the effect of this on anti-tumour immunity and response to treatment.
A Randomised Phase III Trial Of Anastrozole For Breast Cancer Prevention In Postmenopausal Women At High Risk.
Funder
National Health and Medical Research Council
Funding Amount
$1,593,125.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. This project (IBIS 2) is designed to continue the work started by the IBIS 1 prevention trial in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS 1 investigated the use of tamoxifen as a preventative agent for women with moderate to increased risk of developing breast cancer and was found to prevent 48% of oestrogen receptor positive breast cancers. IBIS 2 ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. This project (IBIS 2) is designed to continue the work started by the IBIS 1 prevention trial in determining whether a chemopreventive strategy towards breast cancer is beneficial. IBIS 1 investigated the use of tamoxifen as a preventative agent for women with moderate to increased risk of developing breast cancer and was found to prevent 48% of oestrogen receptor positive breast cancers. IBIS 2 investigates anastrozole (Arimidex) as a preventative agent for women with moderate to increased risk of developing breast cancer. It is a multi-centre, randomised, double blind control trial which has the potential to benefit many millions of women worldwide. Anastrozole is an aromatase inhibitor (AI). AIs are a class of endocrine drug which have been shown to be at least as effective as tamoxifen but without the serious side effects seen with tamoxifen. Anastrozole has been shown to be 60% better than tamoxifen in preventing a second breast cancer in women already diagnosed with breast cancer. Women who participate in this study will be postmenopausal with a relative risk of at least two-fold of developing breast cancer. They will be randomised to receive either anastrozole or placebo as a daily tablet, and neither the woman nor her treating clinician will know which treatment has been allocated (double blind study). To investigate whether anastrozole effects bone density, a baseline bone density scan will be measured prior to study entry. This sub-study will investigate bone density in greater detail and the potential role of bone preserving treatment (bisphosphonate). The primary endpoint for the IBIS 2 study is the development of histologically confirmed breast cancer, invasive or non-invasive.Read moreRead less
Follow-up Phase Of A Randomised Trial Of Tamoxifen Or Placebo For Breast Cancer Prevention In High Risk Women.
Funder
National Health and Medical Research Council
Funding Amount
$459,900.00
Summary
Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by over a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study is called IBIS1 (International ....Each year over 10,000 new cases of breast cancer are diagnosed in Australia and over 2500 women die. Tamoxifen, a non-toxic tablet used to control the growth of breast cancer, has safely been taken by over a million women long term . This project measures tamoxifen's role in preventing breast cancer in high risk women compared to placebo, in a randomised double blind clinical trial. The trial has the potential to benefit many millions of women worldwide. The study is called IBIS1 (International Breast cancer Intervention Study) , and is conducted in Australia by the Australian New Zealand Breast Cancer Trials Group (ANZ BCTG), and internationally by the Imperial Cancer Research Fund (ICRF) in London. On the trial women have regular, annual mammography, 6 monthly clinical checks and take a tablet each day called TAMPLAC, which is either tamoxifen or placebo. The accrual phase has been funded by the NHMRC and by November 2000 the target number of women on the trial was reached ahead of schedule - over 7000 internationally including over 2500 from Australia. Follow-up is being completed with planned data analysis within the next three years. Funding for this phase in Australia is now being sought. The ANZ BCTG and over 2500 women at increased risk of breast cancer have demonstrated a remarkable commitment to complete accrual. It is now vitally important that the essential follow-up with careful monitoring is completed to facilitate anaysis of the data at the earliest opportunity. The only other large randomised trial testing tamoxifen (NSABP P-1) ceased and unblinded in 1998, with an average follow-up of less than 4 years. This trial has had to re-commence follow-up to determine longer term tamoxifen effects. The IBIS 1 study is now the only large, blinded trial remaining in the world, and it's follow-up is of very high international importance. The completion of follow-up and the publication of results will have substantial impact worldwide.Read moreRead less
IBIS II: A Randomised Phase III Trial Of Anastrozole For Breast Cancer Prevention In Postmenopausal Women At High Risk.
Funder
National Health and Medical Research Council
Funding Amount
$1,732,559.00
Summary
The IBIS II trial builds on the successful IBIS 1 breast cancer (BC) prevention trial in determining whether a chemopreventive strategy towards BC is beneficial. Women who are postmenopausal with an increased risk of BC are randomised to receive either anastrozole (an aromatase inhibitor) or placebo as a daily tablet. Neither the woman nor her clinician know which treatment has been allocated (double blind study). IBIS 2 has the potential to benefit many higher risk women worldwide.
A Randomised Trial Of Adjuvant Chemotherapies In Resectable Pancreatic Cancer: ESPAC-3
Funder
National Health and Medical Research Council
Funding Amount
$430,500.00
Summary
Over 1,650 Australians are diagnosed with pancreatic cancer each year. In most cases, surgery will remove the tumour but it is possible that the cancer will return as a result of undetectable disease (micrometastases). The cancer will return and be incurable in the majority of patients. More than 1600 Australians die of the disease every year. This study compares the impact of adding chemotherapy to surgery alone (the current standard of care). The study will also compare the effectiveness of tw ....Over 1,650 Australians are diagnosed with pancreatic cancer each year. In most cases, surgery will remove the tumour but it is possible that the cancer will return as a result of undetectable disease (micrometastases). The cancer will return and be incurable in the majority of patients. More than 1600 Australians die of the disease every year. This study compares the impact of adding chemotherapy to surgery alone (the current standard of care). The study will also compare the effectiveness of two different types of chemotherapy. Surgical resection of a pancreas tumour is the current standard of care for this disease. It is possible that people treated with chemotherapy after their tumour has been surgically removed may live longer before their disease returns and may liver longer overall. This has been shown to be true in other in cancers; eg. breast and bowel. The side effects of chemotherapy are important and can be severe in some people. Recent studies in advanced pancreatic cancer have suggested that the new drug gemcitabine may be more effective than other drugs. For this reason, the trial compares the outcomes in people treated with gemcitabine to those treated with an older drug 5FU, which has been shown to improve survival in an earlier study by a European group. This trial will determine if chemotherapy in addition to surgery increases the length of time before the disease comes back and survival. If it does, it should become standard practice. This study is an important international initiative that will provide unique information about effectiveness of these treatments and their impact on quality of life from the patient's perspective. This study and the previous European study are the largest of their type ever done. 900 people will take part. This study is being conducted in Australia by the Australasian Gastro-Intestinal Trials in collaboration with the Australian Hepatobilary Association and the NHMRC Clinical Trials Centre.Read moreRead less
Prevention Of Late Breast Cancer (BC) Events In Postmenopausal Women With Endocrine Responsive BC.
Funder
National Health and Medical Research Council
Funding Amount
$4,687,599.00
Summary
This proposal is from Australia's national breast cancer (BC) trials group, the ANZ BCTG, for a new phase III, multi-centre clinical trial evaluating whether much later endocrine therapy with an aromatase inhibitor can prevent BC recurrence in postmenopausal women who have: had hormone sensitive BC at least 6 years ago; were treated by Tamoxifen more than 1 year ago; and, are currently disease free. Subjects will randomly receive letrozole or placebo as a daily tablet for five years.
Sentinel Node Biopsy Versus Axillary Clearance In Early Breast Cancer: The SNAC Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,257,525.00
Summary
Over 10,000 Australian women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spread to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. This study compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) ....Over 10,000 Australian women are diagnosed with breast cancer each year. Most need surgery to remove the cancer and determine if it has spread to glands in the armpit (axillary lymph nodes). Knowing whether the cancer has spread to the axillary lymph nodes helps determine prognosis and plan treatment. Surgical removal is the most reliable way to assess the axillary lymph nodes. This study compares two operations for assessing cancer spread to the lymph nodes in women with early breast cancer: 1) axillary clearance and 2) sentinel node biopsy. Axillary clearance involves removal of most lymph nodes in the armpit. In sentinel node biopsy only a few lymph nodes most closely related to the breast cancer are removed. Axillary clearance is the current standard operation. However, it is associated with risks including infection, pain, stiffness, numbness and lymphoedema (arm swelling). Lymphoedema may occur in 5-50% of women treated for breast cancer and can cause major symptoms and disabilities. In many women the breast cancer has not spread to the lymph nodes, and axillary clearance is unnecessary. Recent studies suggest sentinel node biopsy may provide as much information as axillary clearance. Scans and dye are used to help locate the sentinel nodes. Minimising the amount of surgery to the armpit should reduce the side effects. However, the long term safety and effectiveness of removing only a few nodes is unknown. This trial will determine if sentinel node biopsy reduces lymphoedema and gives equivalent cure rates. If it does, then it should become standard practice. The study compliments comparable studies being done in US, UK and Europe by providing unique information about symptoms and quality of life from the women's perspective. One thousand Australian women will take part. The is study is being conducted by Australian breast surgeons under the auspices of the Royal Australasian College of Surgeons and the NHMRC Clinical Trials Centre.Read moreRead less
Optimal Duration Of Neoadjuvant Androgen Deprivation Therapy In Localised Prostate Cancer Treated By Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$422,335.00
Summary
The 96.01 trial aims to find out whether androgen deprivation (AD) administered prior to and during radiotherapy (i.e., neo-adjuvant AD) will improve outcomes in patients with locally advanced prostate cancer that is considered inoperable and is treated for cure by radiotherapy. The trial also aims to find out whether six months AD produces outcomes superior to those achieved by three months AD. The trial has been running since 1996 and involves 802 men who attend 19 cancer treatment centres acr ....The 96.01 trial aims to find out whether androgen deprivation (AD) administered prior to and during radiotherapy (i.e., neo-adjuvant AD) will improve outcomes in patients with locally advanced prostate cancer that is considered inoperable and is treated for cure by radiotherapy. The trial also aims to find out whether six months AD produces outcomes superior to those achieved by three months AD. The trial has been running since 1996 and involves 802 men who attend 19 cancer treatment centres across Australia and New Zealand. It would not have been possible without the continuous funding support of the NHMRC. So far this trial has shown that AD does prevent prostate cancer from returning after radiotherapy. This is very important because the need for treatment of recurrent cancer (usually AD for the rest of the patient's life) is halved by 6 months AD compared to standard treatment (radiotherapy alone). However, it is now necessary to observe the patients in this trial for another 5 years to find out whether AD also prolongs life, and whether 6 months AD is more effective than 3 months. Further patient follow up is also necessary to identify whether some men respond better to treatment than others. This is very important because it will enable treatment to be tailored to individual patients, in particular those who require more treatment than is given in this trial. This funding application is therefore to enable patient follow up on this large scale trial for another 5 years.Read moreRead less