A Study of IMRT in Primary Bone and Soft Tissue Sarcoma

IMRiS is a phase II trial which aims to assess the feasibility, efficacy and toxicity of Intensity Modulated Radiotherapy (IMRT) in three different cohorts of patients with primary bone and soft tissue sarcoma and to demonstrate whether IMRT can improve on current clinical outcomes.

Cohort 1 of the trial is now closed to recruitment.

IMRiS is a prospective multicentre phase II trial of Intensity Modulated Radiotherapy (IMRT). The trial is aiming to evaluate the role of intensity modulated radiotherapy (IMRT) in soft tissue and bone sarcomas. Three separate sarcoma cohorts will be studied and will be analysed separately. Patients will be enrolled in one of three cohorts depending on the type of sarcoma they have:

Cohort 1- Patients with Limb/limb girdle soft tissue sarcoma receiving (neo)-adjuvant radiotherapy. (closed to recruitment)

Cohort 2- Patients with Ewing sarcoma of the spine/pelvis receiving definitive radical or (neo)-adjuvant radiotherapy.

Cohort 3- Patients with non-Ewing primary bone sarcomas of the spine/pelvis receiving definitive radical or adjuvant radiotherapy.

Dose schedules for each Cohort have been indicated in the Trial Arm description.

Radiotherapy will be delivered with fixed beam IMRT, arc IMRT techniques, or tomotherapy. All trial patients will be followed up until death or a maximum of three years from the date of registration in the trial.

The theoretical advantage to IMRT is the potential reduction in late toxicity and subsequent potential for functional improvement. There have been no prospective studies to date powered to address this, particularly where IMRT is used post-operatively. IMRiS cohort 1 will address this question and establish if the use of IMRT will reduce late normal tissue toxicity.

In cohorts 2 \& 3, the aim is to establish if the use of IMRT will enable the achievement of a radiotherapy treatment plan that delivers the optimal dose while keeping within normal tissue tolerances. There have been no clinical trials of IMRT in Ewing sarcoma and there is very little published on the use of IMRT in high grade bone sarcomas and chordomas. It is important to establish the feasibility of IMRT to achieve the required radiation doses to the tumour, and to prospectively document the side effects of treatment in this setting. IMRiS will address this in cohort 2 and cohort 3.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically proven soft tissue sarcoma of the upper or lower limb or limb girdle (Cohort 1), OR,

   Ewing sarcoma of bone arising in the pelvis or spine (Cohort 2) , OR,

   High grade primary bone sarcoma (non-Ewing) or Chordoma arising in the pelvis/spine (Cohort 3)
2. Patients requiring (neo)adjuvant or definitive radical radiotherapy
3. WHO performance status 0-2
4. Patients aged 16 years or more
5. Patients fit enough to undergo radiotherapy treatment and willing to attend follow up visits as per protocol
6. Women of child-bearing potential must have a negative pregnancy test prior to trial entry. Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment.
7. Capable of giving written informed consent

Exclusion Criteria:

1. Previous radiotherapy to the same site
2. Patients receiving concurrent chemotherapy with radiotherapy (neo-adjuvant chemotherapy prior to radiotherapy is permitted.
3. Patient with bone sarcomas eligible for proton beam radiotherapy; N.B. if a patient is not to have PBRT for whatever reason, they may be considered for IMRiS.
4. Paediatric type alveolar or embryonal rhabdomyosarcomas
5. Pregnancy (Women of child-bearing potential must have a negative pregnancy test prior to trial entry. Female patients of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods, which must be continued for 3 months after completion of treatment
6. Patients with concurrent or previous malignancy that could compromise assessment of the primary and secondary endpoints of the trial; these cases must be discussed with UCL CTC prior to the patient being approached.