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

Sponsor

Oslo University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT00790244

Collaborator

Scandinavian Sarcoma Group (Other)

188

Enrollment

Locations

Arms

180

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Soft Tissue Sarcoma Non Metastatic Disease	Drug: doxorubicin , ifosfamide Drug: doxorubicin, ifosfamide Drug: doxorubicin, ifosfamide Drug: doxorubicin, ifosfamide	Phase 2

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

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

Anticipated Enrollment :

188 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2007

Anticipated Primary Completion Date :

Oct 1, 2012

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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)	Drug: doxorubicin , ifosfamide doxorubicin 60mg/m2+ifosfamide 6g/m2 every third week Other Names: Doxorubicin Holoxan Drug: 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 four. (>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2) Other Names: Doxorubicin Holoxan
Experimental: 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)	Drug: doxorubicin , ifosfamide doxorubicin 60mg/m2+ifosfamide 6g/m2 every third week Other Names: Doxorubicin Holoxan
Experimental: 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)	Drug: doxorubicin , ifosfamide doxorubicin 60mg/m2+ifosfamide 6g/m2 every third week Other Names: Doxorubicin Holoxan Drug: 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) Other Names: Doxorubicin Holoxan
Experimental: Arm 1 <70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle (>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)	Drug: doxorubicin , ifosfamide doxorubicin 60mg/m2+ifosfamide 6g/m2 every third week Other Names: Doxorubicin Holoxan Drug: doxorubicin, ifosfamide Doxorubicin and Ifosfamide given every three weeks, totally 6 courses. Other Names: Doxorubicin Holoxan

Outcome Measures

Primary Outcome Measures

Metastases-free survival [time frame from start of treatment until the events metastases or death of any cause]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scandinavian Sarcoma Group Secretariat	Lund University Hospital	Lund	Sweden	SE-221 85
2	Scandinavian Sarcoma Group centers	Lund		Sweden	221 85

Sponsors and Collaborators

Oslo University Hospital
Scandinavian Sarcoma Group

Investigators

Principal Investigator: Kirsten Sundby Hall, MD,PhD, c/o: Scandinavian Sarcoma Group, Southern Swedish Regional Tumor Registry, Lund University Hospital, SE-221 85 Lund