Clinical trial NCT04132895: ICONIC: Improving Outcomes Through Collaboration in OsteosarComa
Official title: ICONIC: Improving Outcomes Through Collaboration in OsteosarComa
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteosarcoma
Keywords: Osteosarcoma
Biobank
Genomics
Tumour markers
ImmuneOncology
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Bone Cancer Research Trust
First posted: 2019-10-21
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients diagnosed with osteosarcoma in the UK at the time of the Study.

Brief summary: There has been little improvement in outcome for patients with osteosarcoma (OS) over the last 20 years. There have been only a few clinical trials of new treatments and no major new therapies introduced recently. This is in part because there is no good understanding of the biology of osteosarcoma, but also trials have only included subgroups of patients. The more that is understood about how and why osteosarcoma arises and grows the better clinicians will be able to decide what treatments are most likely to work best.

The purpose of this project is to collect high quality clinical data about patients of all ages with osteosarcoma, such as information about the size of the disease, how it was diagnosed and where it is at diagnosis, what treatments were given and how the disease responded the treatments.

Blood and tissue samples will also be collected for analysis in research laboratories. By looking at the results of the laboratory findings and the clinical data together, the questions will start to be answered about why osteosarcomas arise and grow, what makes it spread, and why some patients respond to treatment better than others. As time goes on, this information is planned to be used to develop clinical trials of new treatments.

Alongside this, the aim is to find out more about how osteosarcoma and its treatments affect the lives of those living with this disease. This information will help provide the most appropriate care and support that will meet the needs of each patient.

Ultimately, the aim is to improve the care and treatment of osteosarcoma patients so that they may live longer and better lives.

Detailed description: Osteosarcoma is the most common bone sarcoma, accounting for approximately 30% of all bone sarcoma diagnoses. In England, it accounts for approximately 130 cases per year across all ages.

Generally osteosarcoma has an early peak in adolescent patients, with a second peak in patients over 60 years of age. There are differing treatments, including chemotherapy with more than one drug and surgery to the primary site - and for metastases where these occur.

Outcome, however, has improved little over the past 25 years with the proportion of patients surviving to 5 years remaining at about 42% for all ages and stages in the UK. Patients under 40 years of age (52%) are more likely to survive for 5 years than patients over 40 years (25%).

Survival also depends on the primary site of the osteosarcoma. It is poor for patients with tumours that are not in the limbs, at 36% for patients under the age of 40 years and as low as 6% for patients over 40 years. Also patients with metastatic disease at diagnosis still have a poor outcome.

The use of chemotherapy and surgery depends on factors such as age, the site of the osteosarcoma, how far spread it is and how well the patient is generally, with approximately two thirds of patients currently receiving chemotherapy, radiotherapy and surgery in England each year.

The most recent randomised trial for osteosarcoma, EURAMOS-1 \[A randomized trial of the European and American Osteosarcoma Study Group to optimize treatment strategies for resectable osteosarcoma based on histological response to pre-operative chemotherapy\], was an excellent example of an international effort to seek improved treatments for a rare cancer. Despite the participation of over 2000 patients, there were no changes to the standard of care for osteosarcoma.

There is still an unmet need to find new approaches, including biomarkers and new, targeted patient specific therapeutic approaches to improve outcomes for this group. This includes searching for improved systemic treatments and better approaches to management of the osteosarcoma. The ICONIC Study will provide a dataset for translational research into osteosarcoma.

Osteosarcoma clinical trials to date have focussed on a limited number of outcomes, usually in the younger patients with a tumour in a limb. So addressing complex inter-related questions has not been possible and several subpopulations of patients have not been studied. This limits opportunities to improve the standard of care. These groups include:

* patients with widely spread (metastatic) disease;
* patients with tumours in the less common locations such as the pelvis, spine and skull;
* patients with osteosarcoma with a background of skeletal abnormalities or an underlying genetic predisposition;
* the 50% of osteosarcoma arising in patients over 40 years.

Little is currently known about factors influencing treatment decisions in these groups and how consistently a standard of care is applied. The effect of treatments on quality of life, patient reported outcomes and other performance assessments is also not well described or understood. As osteosarcoma is quite rare it can be difficult for General Practitioners (GPs) to identify symptoms and patients often wait a long time before tests for osteosarcoma are carried out. How this affects outcomes is not known.

Overall, there is a need to broaden the ambition and scope of osteosarcoma research while improving access for all patients.

Eligibility criteria: Inclusion Criteria:

* New histological diagnosis of osteosarcoma or in the absence of osteoid seen on biopsy, pathology and imaging supportive of a diagnosis of osteosarcoma. (It is well recognised that some patients may present with features suggestive of osteosarcoma (under 40 years, radiological abnormality compatible) but in whom no osteoid is detected in needle biopsy. Although categorised as spindle cell tumour of bone, such patients are usually treated in an identical approach to osteosarcoma. A definite diagnosis of osteosarcoma is then often possible after surgery when the entire resection specimen is available.)
* Written informed consent of patient and/or parent/legal guardian.

Exclusion Criteria:

• Diagnosis more than four months prior to registration.

Primary outcomes:
measure: Feasibility phase: Patient recruitment.
timeFrame: One year from study opening.
measure: Main Study: Patient recruitment
timeFrame: 3 years from study opening.
Secondary outcomes:
measure: Correlation of chemotherapy and radiotherapy to outcome
timeFrame: 4 years from registration.
measure: Do tumour margin and response to chemotherapy predict local recurrence in OS?
timeFrame: 4 years from registration.
measure: Correlation of tumour heterogeneity and clonal evolution to chemotherapy response and patient outcome.
timeFrame: 4 years from registration.
measure: Validation of whole genome sequencing
timeFrame: 4 years from registration.
measure: Analysis of circulating biomarkers
timeFrame: 4 years from registration.
measure: Patient reported outcomes
timeFrame: 4 years from registration.
measure: Analysis of PMBCs for IO research
timeFrame: 4 years from registration.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College Hospitals London NHS Foundation Trust
state: Greater London
city: Aberdeen
country: United Kingdom
facility: NHS Grampian Health Board
city: Birmingham
country: United Kingdom
facility: Birmingham Women's and Childrens NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: The Royal Orthopaedic Hospital NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University LHB
city: Edinburgh
country: United Kingdom
facility: NHS Lothian Health Board
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde Health Board
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Oswestry
country: United Kingdom
facility: The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Children's NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: University College Hospitals London
name: Sandra Strauss, MD
role: PRINCIPAL_INVESTIGATOR
References: