- Toon alles
- gastro-intestinal stromal tumor
- synovial sarcoma
- atypical lipomatous tumor
- well-differentiated liposarcoma
- undifferentiated pleomorphic sarcoma
- dedifferentiated liposarcoma
- myxoid liposarcoma
= DSG Endorsed
A 3 Arm Randomized Study on Health-related QoL of Elderly Patients With Advanced Soft Tissue Sarcoma (Tolerance)
A 3 arm randomized study on health-related quality of life of elderly patients with advanced soft tissue sarcoma undergoing Doxorubicin Alone Every Three Weeks or Doxorubicin Weekly or Cyclophosphamide Plus Prednisolone Treatment
Een 3-arm gerandomiseerde studie over gezondheidsgerelateerde kwaliteit van leven bij oudere patienten met vergevorderde weke delen sarcomen.
This is a multi-centre, open label, randomized phase 3 selection study (1:2:2 randomization).
After confirmation of the eligibility criteria, 185 patients will be randomized 1:2:2 to either the control arm (doxorubicin 60-75 mg/m² IV every 3 weeks) or experimental arm 1 (doxorubicin 12 mg/m2 IV every week) or experimental arm 2 (cyclophosphamide 100 mg orally BD plus prednisolone 10-20 mg orally on day 1 to day 7 of each 14 day cycle).
Health-related quality of life (HRQoL) assessment will be performed every 3 weeks during the first 12 weeks and every 12 weeks thereafter until month 12 after start of treatment.
Disease evaluation will be performed every 12 weeks until progression. The primary endpoint of the study is difference among the study arms in physical and role functioning at 12 weeks.
- Histologically proven advanced unresectable or metastatic soft tissue sarcoma
- Representative formalin fixed, paraffin embedded tumor blocks or a minimum of 10 unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review. Histological central review is not required before treatment start but it is mandatory to send at least 10 unstained tumor slides (blocks optional) at time of study entry. Local histopathological diagnosis will be accepted for entry into this trial.
- Age ≥ 65 years of age (patients between 65 and 69 years old are eligible if G8 score ≤ 14; patients ≥ 70 years old are eligible independent of G8 score)
- WHO performance status 0 – 2
- Life expectancy based on other significant morbidity of ≥ 6 months
- Presence of measurable disease (according to RECIST 1.1), as confirmed by imaging within the 28 days prior to randomization. CT with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT + MRI.
- Progressive disease at entry based on RECIST 1.1
- Patients amenable to receive doxorubicin according to investigator’s assessment
- Adequate haematological and organ function assessed prior to randomization:
- Haematological function:
- Haemoglobin ≥ 9.0 g/dL or 5.6 mmol/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Coagulation: partial thromboplastin time (PTT) ≤ 1.0 times upper limit of normal (1.0 x ULN) of institutional limits and prothrombin time (PT) ≤ 1.0 x ULN of institutional limits
11. Renal function: estimated glomerular filtration rate (eGFR) > 50 ml/min/m2 (calculated by the MDRD formula in appendix E); no proteinuria ≥ grade 2 (CTCAE version 5.0);
12. Hepatic function: bilirubin ≤ 1.0 x ULN of institutional limits, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤1.5 x ULN.
If isolated elevated bilirubin <2 x ULN and Gilberts syndrome suspected, suggest repeating bloods after food. If bilirubin improves to meet the criteria above this is acceptable. More severe persistent hepatic impairment of whatever cause would exclude the patient from treatment till resolved.
13. Cardiac function: clinically normal function based on the institutional lower limit of normal for left ventricular ejection fraction (LVEF) as assessed either by multi-gated acquisition scan (MUGA) or cardiac ultrasound and 12 lead electrocardiogram (ECG) without clinically relevant abnormalities. Measurement should include investigator assessment of a potential participant’s risk for heart failure with a validated clinical classification system, i.e. the New York Heart Association Functional Classification. Only patients with NYHA class 1 and 2 according to appendix D are eligible.
13. Completion of EORTC QLQ-C30 and EORTC QLQ-ELD14 at baseline.
14. Assessment of G8 geriatric screening tool
15. Assessment of Katz Index of Independence in Activities of Daily Living (ADL)
16. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
17. With female partners of childbearing potential, men must remain abstinent or use a condom during the treatment period and for a period of 6 months after the last dose of doxorubicin-based chemotherapy and for a period of 12 months after the last dose of cyclophosphamide-based chemotherapy. Men must refrain from donating sperm during this same period. Contraception should be considered for the female partners of childbearing potential as well.
18. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for a period of 6 months after the last dose of doxorubicin-based chemotherapy and for a period of 12 months after the last dose of cyclophosphamide-based chemotherapy to avoid exposing the embryo.
19.Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations including commitment to completing questionnaires during the course of the study.
- Symptomatic or known brain metastasis
- Any prior treatment with anthracyclines
- Any prior systemic treatment for metastatic STS
- Inability to swallow and/ or retain oral tablets
- Rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Hypersensitivity to doxorubicin, cyclophosphamide, prednisolone or to any of their metabolites or to any of their excipients
- Uncontrolled severe illness, including but not limited to:
- Congestive heart failure
- Angina pectoris
- Acute inflammatory heart disease
- Myocardial infarction within 1 year before randomization
- Arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy
- Uncontrolled cardiac arrhythmia
- Increased haemorragic tendency
- Uncontrolled diabetes
- Bone marrow aplasia
- Active or uncontrolled infections among which those requiring systemic antibiotics or antimicrobial therapy.
- Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
- Vaccination with live vaccines within 30 days prior to study entry
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
- Known contraindication to imaging tracer or contrast medium and contraindication to MRI
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and its active requirements (including completion of questionnaires) and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
Registration study on bone and soft tissue sarcoma
To prospectively and retrospectively collect data of patients with bone or soft tissue sarcoma in the Netherlands to improve the knowledge and therefore the treatment care.
Een lange termijn onderzoek naar de behandeling en uitkomsten van bot en weke delen sarcomen
Registration study sarcoma
Observational study (observational cohort study)
To prospectively and retrospectively collect data of patients with bone or soft tissue sarcoma in the Netherlands to improve the knowledge and therefore the treatment care. Besides to create a continuous basis for a large variety of research purposes including prognostic and predictive research, health care policies and cost-effectiveness studies.
- Age ≥ 18 years
- Histologically proven bone or soft tissue sarcoma, excluding Gastrointestinal Stromal Tumours
- Altered mental status that would prohibit the understanding of any giving of informed consent
Name: dr. P.M. Braam
Address: Radboudumc, Geert Grooteplein Zuid 32, 6525 GA Nijmegen
Towards a Minimally Invasive Approach of Atypical Lipomatous Tumors: the MINIMALIS trial
To develop a minimally invasive approach of both diagnosing and treating atypical lipomatous tumors, saving these patients a biopsy, surgery-related complications and morbidities amongst others.
Op weg naar een minimaal invasieve benadering van atypische lipomateuze tumoren: de MINIMALIST studie
Prospective single center observational cohort study. Two-arm parallel assignment (active surveillance or surgery).
Rationale: Patients with an atypical lipomatous tumor (ALT) have an excellent prognosis, approaching 100% survival after 10 years of follow-up. Currently, we might be ‘overtreating’ these patients with surgery and radiotherapy, thereby inducing morbidity and even mortality. Despite this excellent prognosis, active surveillance is barely applied in these patients. Furthermore, survival might not be the only appropriate outcome to measure, and other outcomes, such as health-related quality of life (HRQoL), might have become more relevant. Second, it can be very difficult to distinguish between ALTs and lipomas based on imaging. Therefore, these patients currently need a painful and invasive biopsy for pathological examination to make the distinction. Finally, due to the rarity and heterogeneity of liposarcomas, it is a challenge to collect a large homogeneous set of tissue samples for translational research.
Objective: The aim is to develop a minimally invasive approach of both diagnosing and treating ALTs, saving these patients a biopsy, surgery-related complications and morbidities amongst others. As a first step towards a minimally invasive diagnosis, a radiomics model was developed on a retrospective cohort to distinguish lipomas from ALTs based on MRI scans. In the current study, one of the objectives is to prospectively validate this radiomics model. Second, to prevent the ‘overtreatment’ of ALT patients, the aim is to explore the feasibility and safety of active surveillance (AS) as a treatment option for ALTs, including evaluating the HRQoL. Lastly, the objective is to build a biobank of the biopsies and, if applicable, resection specimens obtained during the study for future translational research.
- Aged ≥18 years
- Primary or recurrent lipomatous tumor suspected for lipoma or atypical lipomatous tumor
- Adequate understanding of the Dutch or English language (to fill out the HRQoL questionnaires)
- Tumor localization in the mediastinum, retroperitoneum or testis/scrotum
- Diagnosis through excisional biopsy
- Any type of treatment for the current tumor (i.e. in case of recurrence, treatment of the prior tumor(s) is allowed)
- Signs/suspicion of dedifferentiation in the biopsy specimen at time of diagnosis
- Unable to undergo regular MRI-scans (for example because of a pacemaker, claustrophobia)
- Systemic treatment for any other concurrent malignancy
- Currently receiving radiotherapy at affected site for other concurrent disease
- Incapable to understand the study, to sign informed consent or to fill out the HRQoL-questionnaires
Name: Anne-Rose Schut
Phone: 010 704 12 23