Clinical Trials
Clinical Cancer trials are ongoing for almost every type of cancer. Most of these trials are solely based on clinical data which to a certain degree reduces our ability to better understand how this disease operates. In contrast ACGT focuses on the integration of multilevel biomedical data significantly increasing clinicians? ability to better understand cancer and thus help with the design of better therapies for higher cure rates.
ACGT clinico-genomic trials are devoted to archiving and analysing individual patient data on associations to molecular genetic findings with the ultimate objective of developing more individualized treatments for cancer patients. At the moment two clinical trials use the ACGT platform: the TOP trial for breast cancer and the SIOP 2001/GPOH trial for nephroblastoma, the most common childhood kidney cancer.
The SIOP 2001/GPOH trial is a multicentre prospective randomized trial to evaluate the necessity of anthracyclines (doxorubicin, a cytostatic drug with the potential risk of heart disease (cardiomyopathy) as a late effect) in the treatment of unilateral non-metastasized nephroblastoma. Diagnosis is solely done by imaging studies. Patients enrolled in the trial will receive preoperative chemotherapy with Vincristin and actinomycin for 4 weeks followed by surgery of the tumour (tumornephrectomy). After surgery patients are stratified according to their individual risk based on histological subtype and local stage. Only patients with intermediate risk tumours and a local stage II or III are eligible for randomization with or without doxorubicin. Patients with low risk tumours or high risk tumours do receive standard treatment according to their risk factors. 60 % of patients will hav ea local stage I and treated with only 4 weeks of postoperative chemotherapy. More than 90 % of these patients will be cured and survive. Treatment of patients with metastatic disease is stratified after surgery according to their response to preoperative chemotherapy. Those with a complete remission after preoperative chemotherapy will get less treatment than those with remaining tumour. Even patients with metastatic disease can be cured in 80 %. About 5 % of children will be diagnosed with a bilateral kidney tumour. They will be treated in a more individualised way. Again 80 % of them will be cured and do not need dialysis for impaired kidney function. Nephroblastoma is one of the success stories in cancer, where clinical trials did help to reverse prognosis during the last decades. Today the integration of molecular biology into clinical trials is an absolute must as done by ACGT.
For more information please visit:
ACGT: Nephroblastoma:
eu-acgt.org/select-a-category/general-public/cancer-information/nephroblastoma.html
National Cancer Institute: Wilms Tumor and other childhood kidney tumors.
www.cancer.gov/cancertopics/pdq/treatment/wilms/patient/
The TOP trial aims to identify biological markers associated with pathological complete response to anthracycline therapy (epirubicin), one of the most active drugs used in breast cancer treatment. To this end, the neoadjuvant approach is very attractive, as it provides an in vivo assessment of treatment sensitivity without affecting adversely survival. To identify these predictive markers, the trial focuses on gene-expression profiling based on microarrays as well as on the genotyping technology.
Clinicians and other practitioners involved in the ACGT trials are supported by a variety of software resources. One of these resources is called ObTiMA (Ontology based Trial Management for ACGT). This tool which is currently under development enables the chairman of a clinical trial to set up and manage multi-centric trials from a single interface. This is not a trivial task at all and has eluded many efforts to date, primarily because of the complexity of the task but also because of the incompatible data formats and semantics of systems currently in use at hospitals.
One of the main components of ObTiMA is the CRF Creator, which allows a chairman to capture data definitions for a clinical trial in a standardized way. Another component of ObTiMA is the Trial Outline Builder used for writing the Trial Protocol (essentially the plan of the Trial). With the help of templates given by an integrated Master Protocol the chairman of a trial will be guided through all steps of the development of a new trial which will be more streamlined and allow data from different trial sites and IT systems to be integrated in a seamless and easy to analyze manner.
From a clinical point of view ObTiMA will help to increase the number of clinico-genomic trials by facilitating the workload involved in creating a new trial. More importantly, patients participating in such trials are expected to benefit from new treatment options that will become available.