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

• ClinicalTrials.gov Identifier: NCT00790244
• Recruitment Status: Recruiting
• First Posted: November 13, 2008
• Last Update Posted: July 6, 2011
• Sponsor: Oslo University Hospital
• Collaborator: Scandinavian Sarcoma Group
• Information provided by: Oslo University Hospital

Tracking Information

• First Submitted Date: November 12, 2008
• First Posted Date: November 13, 2008
• Last Update Posted Date: July 6, 2011
• Study Start Date: October 2007
• Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 12, 2008): Metastases-free survival [ Time Frame: time frame from start of treatment until the events metastases or death of any cause ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 12, 2008): cumulative incidence of local recurrence,overall survival,acute and late toxicity,secondary malignancies [ Time Frame: for ten years from start of treatment ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Scandinavian Sarcoma Group Protocol for Patients With High-risk Soft Tissue Sarcoma of the Extremities and Trunk Wall
• 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
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Soft Tissue Sarcoma
• Non Metastatic Disease

Intervention

• 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
• 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
• 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

Study Arms

• 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)

  Interventions:

  • Drug: doxorubicin , ifosfamide
  • Drug: doxorubicin, ifosfamide
• 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)

  Intervention: Drug: doxorubicin , ifosfamide
• 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)

  Interventions:

  • Drug: doxorubicin , ifosfamide
  • Drug: doxorubicin, ifosfamide
• Experimental: Arm 1
  <70y: 6 cycles with doxorubicin 60mg/m2+ifosfamide 6g/m2 of each 21day cycle (>=70y: doxorubicin 50mg/m2+ifosfamide 5g/m2)
  Interventions:

  • Drug: doxorubicin , ifosfamide
  • Drug: doxorubicin, ifosfamide

Publications *

• Engellau J, Samuelsson V, Anderson H, Bjerkehagen B, Rissler P, Sundby-Hall K, Rydholm A. Identification of low-risk tumours in histological high-grade soft tissue sarcomas. Eur J Cancer. 2007 Sep;43(13):1927-34. Epub 2007 Jul 12.
• Engellau J, Bendahl PO, Persson A, Domanski HA, Akerman M, Gustafson P, Alvegård TA, Nilbert M, Rydholm A. Improved prognostication in soft tissue sarcoma: independent information from vascular invasion, necrosis, growth pattern, and immunostaining using whole-tumor sections and tissue microarrays. Hum Pathol. 2005 Sep;36(9):994-1002.
• Hall KS, Bruland ØS, Bjerkehagen B, Lidbrink E, Jebsen N, Hagberg H, Papworth K, Hagberg O, Trovik C, Bauer H, Eriksson M. Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study. Clin Sarcoma Res. 2020 Nov 17;10(1):22. doi: 10.1186/s13569-020-00145-5.
• Sundby Hall K, Bruland ØS, Bjerkehagen B, Zaikova O, Engellau J, Hagberg O, Hansson L, Hagberg H, Ahlström M, Knobel H, Papworth K, Zemmler M, Goplen D, Bauer HCF, Eriksson M. Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX). Eur J Cancer. 2018 Aug;99:78-85. doi: 10.1016/j.ejca.2018.05.011. Epub 2018 Jun 19.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 12, 2008): 188
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2022
• Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Kirsten Sundby Hall, MD, PhD; +4722934000; k.s.hall@klinmed.uio.no

Contact: Mikael Eriksson, MD,PhD; +4646177507; mikael.eriksson@onk.lu.se

• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT00790244
• Other Study ID Numbers: EudraCT number 2007-001152-39
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Kirsten Sundby Hall, Rikshospitalet-Radiumhospitalet HF
• Study Sponsor: Oslo University Hospital
• Collaborators: 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

• PRS Account: Oslo University Hospital
• Verification Date: November 2008