Primary Objective: To prospectively identify, in routine daily practice, the impact of radiotherapy to extremities, with regard to the incidence of (severe) ALT or AST elevations in STS patients (all grades, no systemic therapy). Secondary Objective…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue neoplasms
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The incidence of ALT or AST elevations (all grade) in STS patients receiving RT
of the extremities.
Secondary outcome
The prevalence of DNA-damage in peripheral blood mononuclear cells
Background summary
Newly diagnosed non-metastatic Soft Tissue Sarcomas (STS) are primarily treated
by surgery. STS surgery is often combined with preoperative radiotherapy (RT)
to increase local control rates. In the PASART trials, pazopanib was added to
the combined treatment of preoperative RT and surgery in STS patients. During
these trials, unexpectedly, one-third of the patients developed alanine
transaminase (ALT) or aspartate transaminase (AST) elevations. No clear
explanation for this relatively high incidence of these elevations during the
PASART trials has been found, thus far. While treatment with pazopanib
monotherapy may cause CTCAE grade >=3 ALT or AST elevations, the reported
incidence is substantially lower than found during the PASART trials. While the
physiological source of serum ALT and AST is predominantly the liver, both
enzymes can also be found trough out the body such as in the muscles, kidney
and brain. Damage to any of these tissues may cause an elevation of serum ALT
or AST. This suggests that a possible explanation for the observed ALT or AST
elevations during the PASART trials may be due tissue damage as a result of RT.
This may especially be true for STS of the extremities. STS of the extremities
are relatively large and in close proximity to muscles. Irradiation of the
muscles surrounding the STS may be an explanation for the observed ALT or AST
elevations during the PASART trials. Therefore, the primary aim of this study
is identify the impact of radiotherapy to extremities on the incidence of ALT
or AST elevations in STS patients.
The M21SAD (SADDRIN-I) is currently accruing patients. Herein, radiotherapy to
the extremities is combined with the ATM inhibitor AZD1390. In patients
participating to M21SAD, the prevalence of DNA-damage in peripheral blood
mononuclear cells is measured. Now, we have a unique opportunity, within this
N22TAS trial proposal to, also, measure DNA-damage in peripheral blood
mononuclear cells in patients only undergoing radiotherapy without the ATM
inhibitor.
Study objective
Primary Objective:
To prospectively identify, in routine daily practice, the impact of
radiotherapy to extremities, with regard to the incidence of (severe) ALT or
AST elevations in STS patients (all grades, no systemic therapy).
Secondary Objective:
The prevalence of DNA-damage in peripheral blood mononuclear cells.
Study design
A prospective observational study investigating the incidence of ALT or AST
elevations in STS patients receiving RT of the extremities.
Study burden and risks
The patient burden of participation is minimal. During the standard of care
radiotherapy schedule, four additional blood samples will be collected. It is
unlikely participants will experience any complications as a result of the vena
puncture. Patients will not directly benefit form study participation, however
the results of this study will contribute to the understanding of the biology
during radiotherapy in STS patients
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
• Histologically confirmed soft tissue sarcoma for which the standard treatment
includes RT (deep seated and/or >= 5 cm in largest tumor diameter and/ or an
anticipated close resection margin and/or grade II/III according to the FNCLCC
definition);
• The sarcoma mass need to be located in an extremity;
• Able and willing to undergo radiotherapy;
• Able and willing to comply with the drawing of blood samples;
• Age >= 18 years;
• Adequate organ function at start of radiotherapy as defined in Table 4;
• Signed written informed consent prior to any study specific procedures or
sampling;
Exclusion criteria
• Patients with recurrent sarcomas who underwent prior RT to the target lesion
(if the primary sarcoma was managed by surgery only and no perioperative RT,
patients are eligible);
• Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas, bone sarcomas;
• Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol; those conditions
should be discussed with the patient before registration in the trial;
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83144.041.23 |