Hyperthermia and Proton Therapy in Unresectable Soft Tissue Sarcoma (HYPROSAR)

A Phase I/II Study of Concurrent Hyperthermia and Proton Beam Radiotherapy in Primary and Recurrent Unresectable Soft Tissue Sarcoma

This is a multi-institutional phase I/II clinical trial with concomitant local hyperthermia and proton beam radiotherapy in patients with primary or recurrent unresectable soft tissue sarcomas of the extremities, trunk, retroperitoneum (except intrabdominal). The primary purpose would be to assess the safety and efficacy of this approach along with local tumour regressions and subsequent tumour downstaging, thereby enabling a near total removal of these tumours following the hyperthermia and proton beam therapy.

Study Overview

• Status: Unknown
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Radiation: Hyperthermia and Proton Beam

Detailed Description

Hyperthermia would be delivered at Kantonsspital Aarau (KSA) with superficial or deep hyperthermia treatment units as may be appropriate. All patients would undergo a pre-hyperthermia treatment planning and a temperature of around 41.5 Centigrade to 42.5 Centigrade would be aimed during hyperthermia sessions.Hyperthermia would be delivered once a week and the treatment sessions would last for around 60 minutes of active heating.

Proton bean therapy would be carried out at Center of Proton Therapy, Paul Scherrer Institute (PSI), Villigen using scanning beam proton therapy. A preoperative dose of 55 - 60 Gray equivalent (GyE) or those considered for radical treatment, 72-76 GyE would be delivered, 5 days a week at 1.8 - 2 Gy/fr.

On days of both hyperthermia at KSA and proton therapy at PSI, the time interval between the two treatments could be 90 to 150 minutes, taking into consideration the time to travel between the two institutions. Hyperthermia in these days would follow proton beam therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Niloy R Datta, MD, DNB,; Phone Number: +41-62 8389559; Email: niloyranjan.datta@ksa.ch
• Study Contact Backup: Name: Stephan Bodis, MD; Phone Number: +41-62 838 5371; Email: stephan.bodis@ksa.ch

Study Locations

• Switzerland
  • Aargau
    • Aarau, Aargau, Switzerland, CH 5001
      • Recruiting
      • Kantonsspital Aarau
      • Contact: Niloy R Datta, MD, DNB, CCST; Phone Number: 0041 62 8389559; Email: niloyranjan.datta@ksa.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histopathologically proven and classified soft tissue sarcoma (STS) as per the WHO classification (2002). For all primary tumours, biopsy would be done within 2 months prior to registration and reviewed by the study pathologist. For all recurrent tumours, if prior biopsy has been done elsewhere, the histopathology would be reviewed by the study pathologist.

2. Primary STS of extremities, trunk (except intrabdominal) and retroperitoneal which are,

   1. Deemed inoperable by the study surgeon
   2. Not feasible for a limb sparing surgery with possible R0/R1 resection as per the study surgeon,
   3. Patient medically unfit to undergo surgery
   4. Patient refuses surgery

3. Recurrent STS extremities and trunk would be eligible if

   1. Deemed inoperable by the study surgeon
   2. Not feasible for a limb sparing surgery with possible R0/R1 resection as per the study surgeon,
   3. Patient medically unfit to undergo surgery
   4. Patient refuses surgery
   5. Had not received prior radiotherapy to the proposed site of treatment.
4. All patients having extremity STS with stages T2 and G2 or 3 with M0 (Stages IIB and III as per American Joint Committee on Cancer, AJCC 2010), would be included. For patients of STS of trunk, tumours less than 5cm may also be included if they are considered unresectable.
5. Age more than 18 years
6. Eastern Cooperative Oncology Group,ECOG performance scale 0 and 1
7. Female patients must use effective contraception; must not be pregnant or lactating
8. Life expectancy of atleast 2 years based on the age and co-morbidities, but excluding diagnosis of STS
9. Absence of psychological, familial, sociological or geographical condition that could potentially hamper compliance with the study protocol and follow-up schedule
10. Willing to travel to Paul Scherrer Institute for proton therapy and to Kantonsspital Aarau for Hyperthermia treatment.
11. Agree to comply with the protocol
12. Patients must sign a study specific informed consent form prior to registration.

Exclusion Criteria:

1. Histopathology of rhabdomyosarcoma, extraosseous Ewing's, primary neuroectodermal tumour, aggressive fibromatosis (desmoids tumours), dermatofibrosarcoma protuberans, gastrointestinal stromal tumours, osteosarcoma, chondrosarcoma, Kaposi's sarcoma or angiosarcoma of scalp/face/neck
2. Prior radiotherapy to the site of treatment
3. Intrabdominal soft tissue sarcomas
4. Use of neoadjuvant chemotherapy prior to radiotherapy or surgery
5. Patients with regional nodal metastasis
6. Patients with unequivocal distant metastasis
7. No prior or concurrent malignancies other than surgically treated squamous cell or basal cell carcinoma of the skin which are not in the area of the present malignancy or in situ carcinoma of the skin
8. No serious medical illness which would prevent informed consent or limit survival to less than 2 years
9. Active uncontrolled bacterial, viral or fungal infections until these conditions are corrected or controlled.
10. Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator would preclude the patient from meeting the study requirements.
11. Patients having metal implants, pacemakers or clustered markers
12. Patient who had a history of myocardial infarction within the past 12 months

13. No connective disease disorders that contraindicate radiotherapy, e.g., Scleroderma

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Thermoradiotherapy; Patients subjected to the planned therapeutic intervention of local hyperthermia and proton beam therapy

Radiation: Hyperthermia and Proton Beam; Local hyperthermia,once a week for 5 to 7 weeks to a temperature of 41.5 to 42.5 degree Centigrade; Proton beam therapy, 5 days a week at 1.8 - 2.0 GyE per fraction to a dose of 55 - 60 GyE (preoperative) or 72 - 76 GyE (for radical. Patients who have good response at 5 weeks of treatment would be considered for preoperative treatment, while those with unsatisfactory response that could be taken up for at least R0 resection would be treated to a radical dose.; Other Names: 1. Local hyperthermia; 2. Proton beam therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate safety of hyperthermia and proton beam treatment in unresectable soft tissue sarcomas	Acute and late morbidities of the treatment would be evaluated according to the CTCAE 4.0 guidelines during and until 6 months after the treatment	6 months from end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the local response to hyperthermia and proton beam therapy as a preoperative regimen for unresectable soft tissue sarcomaLocal control	Imaging response according to RECIST criteria comparing pretreatment MRI versus post treatment MRI taken 4 to 6 weeks after completion of the study treatment.	6 months following the completion of study treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local disease free survival	Local disease free survival would be computed using the Kaplan-Meir survival statistics	Would be assessed every 6 monthly up to a maximum of 48 months

Collaborators and Investigators

• Sponsor: Kantonsspital Aarau
• Collaborators: University Hospital, Zürich; Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland
• Investigators: Principal Investigator: Niloy R Datta, MD, DNB, Kantonsspital Aarau, Switzerland

Publications and helpful links

General Publications

• Datta NR, Schneider R, Puric E, Ahlhelm FJ, Marder D, Bodis S, Weber DC. Proton Irradiation with Hyperthermia in Unresectable Soft Tissue Sarcoma. Int J Part Ther. 2016 Fall;3(2):327-336. doi: 10.14338/IJPT-16-00016.1. Epub 2016 Dec 30.

Helpful Links

• Kantonsspital Aarau
• Paul Scherrer Institute

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ANTICIPATED): February 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: July 10, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (ESTIMATE): July 22, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 2, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Radiotherapy; Soft Tissue Sarcoma; Proton beam therapy; Phase I/II trial; Hyperthermia,
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Sarcoma; Hyperthermia; Fever
• Other Study ID Numbers: KSA_HYPROSAR1