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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04031677


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04031677
Ethics application status
Date submitted
22/07/2019
Date registered
24/07/2019
Date last updated
3/04/2024

Titles & IDs
Public title
Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma
Scientific title
A Randomized Phase III Study of Neoadjuvant Chemotherapy Followed by Surgery Versus Surgery Alone for Patients With High Risk RetroPeritoneal Sarcoma (RPS)
Secondary ID [1] 0 0
EA7211
Secondary ID [2] 0 0
EORTC 1809-STBSG
Universal Trial Number (UTN)
Trial acronym
STRASS2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Retroperitoneal Sarcoma 0 0
Liposarcoma 0 0
Leiomyosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Surgery
Treatment: Drugs - Preoperative chemotherapy

Other: Standard arm - Surgery alone

Experimental: Experimental arm - Preoperative chemotherapy and surgery


Treatment: Surgery: Surgery
Large en-bloc curative-intent surgery

Treatment: Drugs: Preoperative chemotherapy
- High grade LPS: ADM 75 mg/m2 (or the equivalent EpiADM 120 mg/m2) + ifosfamide 9 g/m2 Q3 weeks
Note: the recommended dose of Ifosfamide can be modified according to national/institutional guidelines, given that the minimum threshold must be 7.5 g/m2 per cycle.
- LMS: ADM 75 mg/m2 + DTIC 1g/m2 Q3 weeks
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease free survival
Timepoint [1] 0 0
7 years from first patient in
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
8 years from first patient in
Secondary outcome [2] 0 0
Local recurrence free survival
Timepoint [2] 0 0
8 years from first patient in
Secondary outcome [3] 0 0
Recurrence free survival
Timepoint [3] 0 0
8 years from first patient in
Secondary outcome [4] 0 0
Distant metastases free survival
Timepoint [4] 0 0
8 years from first patient in

Eligibility
Key inclusion criteria
- Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of
retroperitoneal space or infra-peritoneal spaces of pelvis.

- LMS:

- Any grade LMS can be included

- Minimum size of LMS tumor should be 5 cm

- LPS:

- Diagnosis should be confirmed based on MDM2 (Mouse double minute 2 homolog) and
CDK4 (Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while
proof of MDM2 amplification is highly recommended.

- All grade 3 DDLPS can be included.

- DDLPS with confirmed grade 2 on biopsy can be included when:

- The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de
Lutte Contre Le Cancer), has no necrosis on the biopsy but clear necrosis on
imaging.

- The tumors carry a high risk gene profile as determined by the Complexity
INdex in SARComas (CINSARC-high)

- Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue
slides must be available at baseline for histological central review.

- Unifocal tumor

- Absence of extension through the sciatic notch or across the diaphragm

- Resectable tumor: resectability is based on pre-operative imaging (CT-abdomen,
potentially also with MRI) and has to be defined by the local treating sarcoma team. A
patients is not considered resectable when the expectation is that only an R2
resection is feasible.

- Criteria for non-resectability are:

- Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or
portal vein

- Involvement of bone

- Growth into the spinal canal

- Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the
right atrium

- Infiltration of multiple major organs like liver, pancreas and/or major
vessels

- Tumor not previously treated (no previous surgery (excluding diagnostic biopsy),
radiotherapy or systemic therapy)

- Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by
imaging within the 28 days prior to randomization. CT thorax abdomen pelvis with IV
contrast is the preferred imaging modality. In case of any contra-indications (medical
or regulatory), it is allowed to perform a non-contrast CT thorax + MRI abdomen &
pelvis.

- = 18 years old (no upper age limit)

- WHO (World Health Organization) performance status = 2

- Adequate haematological and organ function:

- Haematological: haemoglobin > 9.0 g/dL or 5.6 mmol/L, absolute neutrophils > 1.5
x 109/L, platelets > 100 x 109/L Note: Platelet transfusions is allowed to
achieve these baseline values

- Renal: estimated glomerular filtration rate (eGFR) > 50 ml/min/m2; No proteinuria
CTCAE = grade 2;

- Hepatic: Bilirubin = 1.0 times upper limit of normal (1.0xULN) of institutional
limits, ALT (alanine aminotransferase) and/or AST (aspartate transaminase) =1.5 x
ULN. If isolated elevated bilirubin <2 x ULN and Gilberts syndrome suspected,
suggest repeating bloods after food. If bilirubin improves to meet the criteria
above this is acceptable. More severe persistent hepatic impairment of whatever
cause would exclude the patient from treatment till resolved.

- Heart: Clinically normal cardiac function based on left ventricular ejection
fraction (LVEF = 50%) as assessed either by multi-gated acquisition scan (MUGA)
or cardiac ultrasound and 12 lead ECG without clinically relevant abnormalities.

- American Society of Anesthesiologist (ASA) score < 3

- Women of child bearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days prior to the first dose of study treatment or surgery.

Note: a woman is considered of childbearing potential (WOCBP), i.e. fertile, following
menarche and until becoming post menopausal unless permanently sterile.

Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral
oophorectomy.

A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be
used to confirm a post-menopausal state in women not using hormonal contraception or
hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single
FSH measurement is insufficient..

- Patients of childbearing / reproductive potential should use highly effective birth
control measures, as defined by the investigator, during the study treatment period
and for at least 6 months after the last dose of treatment or date of surgery. A
highly effective method of birth control is defined as a method which results in a low
failure rate (i.e. less than 1% per year) when used consistently and correctly. Such
methods include:

- Combined (oestrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, transdermal)

- Progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, implantable)

- Intrauterine device (IUD)

- Intrauterine hormone-releasing system (IUS)

- Bilateral tubal occlusion

- Vasectomized partner

- Sexual abstinence (the reliability of sexual abstinence needs to be evaluated in
relation to the duration of the clinical trial and the preferred and usual
lifestyle of the patient)

- Female subjects who are breast feeding should discontinue nursing prior to the first
day of study treatment and until 6 months after the last study treatment.

- Before patient registration/randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Sarcoma originated from bone structure, abdominal or gynecological viscera

- Metastatic disease

- Tumors with extension through the sciatic notch or across the diaphragm

- Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their
metabolites or to any of their excipients

- Persistent myelosuppression

- Myocardial infarction within the last 6 months

- Uncontrolled cardiac arrhythmia

- Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent
900mg/m² EpiADM) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other
anthracyclines and anthracenediones

- Active and uncontrolled infections

- Vaccination with live vaccines within 30 days prior to study entry

- Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the
urine flow.

- Other invasive malignancy within 5 years, with the exception of adequately treated
non-melanoma skin cancer, localized cervical cancer, localized and presumably cured
prostate cancer.

- Uncontrolled severe illness, infection,medical condition (including, uncontrolled
diabetes or hypertension), other than the Primary LPS or LMS of the retroperitoneum.

- Female patients who are pregnant or breastfeeding or female and male patients of
reproductive potential who are not willing to employ effective birth control method.

- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions
should be discussed with the patient before randomization in the trial

- Known contraindication to imaging tracer and to MRI

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/04/2028
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - University Of Queensland - Woolloongabba
Recruitment hospital [2] 0 0
Peter Maccallum Cancer Institute - Melbourne
Recruitment hospital [3] 0 0
Chris O'Brian Life House - Chris O'Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 0 0
QLD 4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
State/province [16] 0 0
New Hampshire
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
North Dakota
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oklahoma
Country [22] 0 0
United States of America
State/province [22] 0 0
Oregon
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
Rhode Island
Country [25] 0 0
United States of America
State/province [25] 0 0
South Dakota
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Utah
Country [28] 0 0
United States of America
State/province [28] 0 0
Virginia
Country [29] 0 0
United States of America
State/province [29] 0 0
Washington
Country [30] 0 0
United States of America
State/province [30] 0 0
Wisconsin
Country [31] 0 0
Canada
State/province [31] 0 0
British Columbia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
Canada
State/province [34] 0 0
Toronto
Country [35] 0 0
Cyprus
State/province [35] 0 0
Stróvolos
Country [36] 0 0
Czechia
State/province [36] 0 0
Brno
Country [37] 0 0
Denmark
State/province [37] 0 0
Copenhagen
Country [38] 0 0
Denmark
State/province [38] 0 0
Aarhus
Country [39] 0 0
France
State/province [39] 0 0
Lyon
Country [40] 0 0
France
State/province [40] 0 0
Montpellier
Country [41] 0 0
France
State/province [41] 0 0
Paris
Country [42] 0 0
France
State/province [42] 0 0
Strasbourg
Country [43] 0 0
France
State/province [43] 0 0
Villejuif
Country [44] 0 0
Germany
State/province [44] 0 0
Lower Saxony
Country [45] 0 0
Germany
State/province [45] 0 0
Dresden
Country [46] 0 0
Germany
State/province [46] 0 0
Mannheim
Country [47] 0 0
Italy
State/province [47] 0 0
Aviano
Country [48] 0 0
Italy
State/province [48] 0 0
Candiolo
Country [49] 0 0
Italy
State/province [49] 0 0
Meldola
Country [50] 0 0
Italy
State/province [50] 0 0
Milano
Country [51] 0 0
Italy
State/province [51] 0 0
Milan
Country [52] 0 0
Italy
State/province [52] 0 0
Padova
Country [53] 0 0
Italy
State/province [53] 0 0
Roma
Country [54] 0 0
Japan
State/province [54] 0 0
Fukuoka
Country [55] 0 0
Japan
State/province [55] 0 0
Kanagawa
Country [56] 0 0
Japan
State/province [56] 0 0
Miyagi
Country [57] 0 0
Japan
State/province [57] 0 0
Nagoya
Country [58] 0 0
Japan
State/province [58] 0 0
Niigata
Country [59] 0 0
Japan
State/province [59] 0 0
Okayama
Country [60] 0 0
Japan
State/province [60] 0 0
Osaka
Country [61] 0 0
Japan
State/province [61] 0 0
Tokyo
Country [62] 0 0
Japan
State/province [62] 0 0
Saitama
Country [63] 0 0
Netherlands
State/province [63] 0 0
Amsterdam
Country [64] 0 0
Netherlands
State/province [64] 0 0
Leiden
Country [65] 0 0
Netherlands
State/province [65] 0 0
Nijmegen
Country [66] 0 0
Poland
State/province [66] 0 0
Warsaw
Country [67] 0 0
Slovakia
State/province [67] 0 0
Bratislava
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Madrid
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Birmingham
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Glasgow
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Leeds
Country [73] 0 0
United Kingdom
State/province [73] 0 0
London
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Newcastle
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Nottingham
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Oxford
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Canadian Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
ECOG-ACRIN Cancer Research Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Anticancer Fund, Belgium
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Australia and New Zealand Sarcoma Association
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Japan Clinical Oncology Group
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multicenter, randomized, open label phase lll trial to assess whether preoperative
chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk
DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease
free survival.

After confirmation of eligibility criteria, patients will be randomized to either the
standard arm or experimental arm.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04031677
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
EORTC HQ
Address 0 0
Country 0 0
Phone 0 0
+3227741611
Fax 0 0
Email 0 0
1809@eortc.org
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04031677

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 89
Peter MacCallum Cancer Centre
Recruitment postcode(s) [1] 93
3000
Funding & Sponsors
Funding source category [1] 72
Government body
Name [1] 72
NHMRC - Medical Research Future Fund (MRFF) - 2020 Rare Cancers Rare Diseases and Unmet Need (RCRDUN)
Address [1] 72
GPO Box 1421 Canberra ACT 2601
Country [1] 72
Australia
Funding source category [2] 73
Other Collaborative groups
Name [2] 73
European Organisation for Research and Treatment of Cancer
Address [2] 73
Avenue Emmanuel Mounier 83/11 1200 Brussels Belgium
Country [2] 73
Belgium
Primary sponsor
Other Collaborative groups
Primary sponsor name
European Organisation for Research and Treatment of Cancer (EORTC)
Primary sponsor address
Avenue Emmanuel Mounier 83/11
1200 Brussels
Belgium
Primary sponsor country
Belgium
Secondary sponsor category [1] 74
Other Collaborative groups
Name [1] 74
Australia and New Zealand Sarcoma Association (ANZSA)
Address [1] 74
305 Grattan Street, Melbourne VIC 3000
Country [1] 74
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 47
Peter MacCallum Cancer Centre HREC
Address [1] 47
305 Grattan Street Melbourne VIC 3000
Country [1] 47
Australia
Date submitted for ethics approval [1] 47
11/06/2021
Approval date [1] 47
12/11/2021
Ethics approval number [1] 47
HREC/65094/PMCC
 
Public notes

Contacts
Principal investigator
Title 329 0
A/Prof
Name 329 0
Anne Hamilton
Address 329 0
Peter MacCallum Cancer Centre 305 Grattan Street Melbourne VIC 3000
Country 329 0
Australia
Phone 329 0
+61 3 85598339
Fax 329 0
Email 329 0
anne.hamilton@petermac.org
Contact person for public queries
Title 330 0
Ms
Name 330 0
Janina Chapman
Address 330 0
Clinical Trial Manager Australia and New Zealand Sarcoma Association 305 Grattan Street Melbourne VIC 3000
Country 330 0
Australia
Phone 330 0
+61 4 14316490
Fax 330 0
Email 330 0
janina.chapman@petermac.org
Contact person for scientific queries
Title 331 0
A/Prof
Name 331 0
Anne Hamilton
Address 331 0
Peter MacCallum Cancer Centre 305 Grattan Street Melbourne VIC 3000
Country 331 0
Australia
Phone 331 0
+61 3 85598339
Fax 331 0
Email 331 0
anne.hamilton@petermac.org