A Scandinavian Sarcoma Group Treatment Protocol for Adult Patients With Non-metastatic High-risk Soft Tissue Sarcoma of the Extremities and Trunk Wall
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Enrollment
- 188
- Locations
- 2
- Primary Endpoint
- Metastases-free survival
Study Overview
Brief Summary
SSG XX is a phase II trial for high-risk soft tissue sarcomas (STS) of the extremities and trunk wall. Prognostic factors (histopathological markers) are used to identify high-risk tumors. SSG XX will evaluate chemo- and radiotherapy given adjuvantly to these patients. In a specified group of patients also preoperatively given therapy will be studied.
Detailed Description
SSG XX, the third adjuvant STS protocol by SSG, is a phase II non-randomized trial in patients with high risk to develop metastases. SSG XX is based on a previous SSG trial (SSG XIII) regarding use of prognostic markers to identify high-risk tumors and include very similar chemo- and radiotherapy treatment schedules compared to SSG XIII, but the new protocol also includes a treatment arm with preoperative chemo- and radiotherapy for patients with an obvious risk for intralesional surgery initially.
Patients: In this new adjuvant protocol SSG adopts an inclusion decision algorithm based on the following criteria: 1.vascular invasion or 2. presence of at least two of the risk factors: tumor size =>8 cm, necrosis or infiltrative growth(all defined microscopically by the pathologist. The system was developed retrospectively by evaluation of 434 primary histologically high grade (III-IV) STS from the SSG registry, and was later validated in a series of 175 patients in which patients with a high risk for metastases (>40 %) and low risk (<15 %) were separated (Engellau J et al.Eur J Ca 2007 43: 1927-34). Inclusion criteria: age ≥ 18 y and <75 y. Primary end point is metastasis-free survival. Local recurrence and toxicity will also be studied.
Treatment: Six cycles of doxorubicin 60mg/m2 and ifosfamide 6g/m2 will be given adjuvantly (to patients ≥ 70y: 50mg/m2 and 5g/m2 ). Dependent on surgical resection margins, 36Gy or 45Gy (1,8Gy per fraction, two fractions daily) will be given interpolated with chemotherapy.
Conclusion: SSG XX will evaluate chemo-and radiotherapy given adjuvantly to patients with STS and high risk for metastases (arm A). In a specified group of patients also preoperatively given therapy will be studied(arm B). Other sarcoma centers are invited to participate in the study.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Group A: Histological high-grade malignancy soft tissue sarcomas of the extremity and trunk wall.
- •Patients fulfilling the high-risk criteria defined above (see detailed description) Group B: Patients with histological high-grade malignancy soft tissue sarcomas of the extremity and trunk wall for whom surgery carries an obvious risk of intralesional margin
- •Other inclusion criteria for therapy group A and group B
- •Age ≥ 18 y and ≤ 75 y
- •WHO grade 0-1
- •Adequate cardiac function (LVEF ≥ 50%)
- •Normal GFR (clearance)
- •Adequate haematologic and liver function
- •All histotypes except those listed below
Exclusion Criteria
- •The following histological types:
- •Extraskeletal osteosarcoma and - chondrosarcoma, Ewing/PNET, rhabdomyosarcoma, Kaposi´s sarcoma, malignant mesenchymoma, clear cell sarcoma, alveolar soft part sarcoma, epithelioid sarcoma
- •Radiation induced sarcoma
- •No previous anthracycline treatment
- •Less than 5 years free of another primary malignancy
- •More than 12 weeks have elapsed since primary surgery (Group A)
- •More than 4 weeks from diagnostic biopsy to start of chemotherapy (Group B)
Arms & Interventions
Arm 2
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle and radiotherapy 36Gy (1.8Gy per fraction, two fractions daily) will be given between cycle 3 and 4.
(>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin , ifosfamide (Drug)
Arm 2
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle and radiotherapy 36Gy (1.8Gy per fraction, two fractions daily) will be given between cycle 3 and 4.
(>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin, ifosfamide (Drug)
Arm 3
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle and radiotherapy 45Gy (1.8Gy per fraction, two fractions daily) will be given between cycle 3 and 4.
(>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin , ifosfamide (Drug)
Group B
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle and radiotherapy 36Gy (1.8Gy per fraction, two fractions daily) will be given between cycle 2 and 3.
(>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin , ifosfamide (Drug)
Group B
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle and radiotherapy 36Gy (1.8Gy per fraction, two fractions daily) will be given between cycle 2 and 3.
(>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin, ifosfamide (Drug)
Arm 1
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle (>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin , ifosfamide (Drug)
Arm 1
<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle (>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Intervention: doxorubicin, ifosfamide (Drug)
Outcomes
Primary Outcomes
Metastases-free survival
Time Frame: time frame from start of treatment until the events metastases or death of any cause
Secondary Outcomes
- cumulative incidence of local recurrence,overall survival,acute and late toxicity,secondary malignancies(for ten years from start of treatment)