A Scandinavian Sarcoma Group Protocol for Patients With High-risk Soft Tissue Sarcoma of the Extremities and Trunk Wall

Phase 2

• Conditions: Soft Tissue Sarcoma; Non Metastatic Disease
• Interventions: Drug: doxorubicin , ifosfamide; Drug: doxorubicin, ifosfamide

• Registration Number: NCT00790244
• Lead Sponsor: Oslo University Hospital

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 Timeline

• Study Start: 2007-10
• Status Verified: 2008-11
• Study First Submitted: 2008-11-12
• Study First Submitted QC: 2008-11-12
• Study First Posted: 2008-11-13
• Last Update Submitted: 2011-07-03
• Last Update Posted: 2011-07-06
• Primary Completion: 2012-10
• Study Completion: 2022-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 188

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3	doxorubicin , ifosfamide	\<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)
Arm 1	doxorubicin , ifosfamide	\<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle (\>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Group B	doxorubicin , ifosfamide	\<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)
Arm 2	doxorubicin , ifosfamide	\<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)
Arm 1	doxorubicin, ifosfamide	\<70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle (\>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
Arm 2	doxorubicin, ifosfamide	\<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)
Group B	doxorubicin, ifosfamide	\<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)

Primary Outcome Measures

Name	Time	Method
Metastases-free survival	time frame from start of treatment until the events metastases or death of any cause

Secondary Outcome Measures

Name	Time	Method
cumulative incidence of local recurrence,overall survival,acute and late toxicity,secondary malignancies	for ten years from start of treatment

Trial Locations

Locations (2)

Scandinavian Sarcoma Group Secretariat; 🇸🇪 Lund University Hospital, Lund, Sweden

Scandinavian Sarcoma Group centers; 🇸🇪 Lund, Sweden