Sequential neoadjuvant ifosfamide and doxorubicin in localized high-grade soft tissue sarcoma of extremities and trunk wall

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Mar 2021 → ongoing

Decision date (initial)

2024-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510185-27-00

EudraCT number

2020-002777-95

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the percentage of patients who achieve radiological response during neoadjuvant chemotherapy using RECIST v1.1.

Secondary objectives 5

1. To assess disease-free survival (DFS) and overall survival (OS)
2. To investigate if TP53 mutations predict response to high-dose alkylating chemotherapy and/or sequential doxorubicin monotherapy in STS
3. To identify molecular markers of therapy response/resistance and survival outcome, beyond TP53 mutations
4. To assess safety and tolerability of the study treatment
5. To assess quality of life during treatment as measured by EORTC QLQC30

Conditions and MedDRA coding

Patients with high-grade soft tissue sarcoma of the extremities and trunk wall

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. ≥ 18 years of age at the time of informed consent.
2. Histological diagnosis of soft tissue sarcoma belonging to one of the following histotypes: a. Leiomyosarcoma b. Malignant peripheral nerve sheath tumor c. Undifferentiated pleomorphic sarcoma d. Myxofibrosarcoma e. Synovial sarcoma f. Pleomorphic liposarcoma g. Pleomorphic rhabdomyosarcoma h. Unclassified spindle cell sarcoma
3. To identify molecular markers of therapy response/resistance and survival outcome, beyond TP53 mutations
4. To assess safety and tolerability of the study treatment
5. To assess quality of life during treatment as measured by EORTC QLQC30
6. Tumor localized in extremity, girdle and/or trunk ...
7. The primary tumor must be available for biopsy collection at protocol inclusion.
8. Patients must have a measurable tumor according to RECIST v1.1.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
10. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments: a. Hemoglobin ≥ 8.0 g/dL b. Neutrophil count ≥ 1.0 x 109/L c. Platelet count ≥ 75 x 109/L d. Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) e. Creatinine clearance ≥ 60 ml/min based on Cockcroft Gault estimation or direct measurement
11. Negative Hepatitis B and C and HIV serology.
12. Adequate contraception in women of childbearing potential (WOCBP) and their fertile partners. WOCBP should have a negative highly sensitive serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. A woman is considered fertile following menarche and until becoming post-menopausal unless permanently sterile (see appendix 5 for definitions). WOCBP should be willing to use one of the mentioned highly effective methods of birth control mentioned below or be surgically sterile, or abstain from heterosexual activity for the course of the study through 1 year after the last dose of study medication. Methods considered as highly effective birth control methods include combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal, injectable, implantable or transdermal), intrauterine device (including hormone-releasing), male condom, bilateral tubal occlusion, vasectomised partner or sexual abstinence

Exclusion criteria 11

1. Any prior therapy for soft tissue sarcoma.
2. Locoregional or distant metastasis as assessed by CT and/or MRI at time of diagnosis. Patients with lung nodules <10 mm of uncertain etiology may be included.
3. Clinical evidence of serious coagulopathy. Prior arterial/venous thrombosis or embolism does not exclude patients from inclusion, unless patient is considered unfit by study oncologist.
4. Urinary obstruction.
5. Known hypersensitivity towards ifosfamide, doxorubicin or pegfilgrastim, their metabolites and other ingredients in the drug administration formulation.
6. New York Heart Association class II-IV heart disease, myocardial infarction within 6 months of diagnosis of soft tissue sarcoma, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure.
7. Left ventricular ejection fraction (LVEF) < 50%.
8. Patients with a prior or concurrent malignant disease whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible. Patients with a XML File Identifier: BHwdoUlYtVp7SkuvRHHClDOTTOw= Page 15/24 history of breast cancer, requiring continued hormonal treatment (e.g. anti-estrogen or an aromatase inhibitor) may be included. Patients with a history of prostate cancer, requiring continued support with luteinizing hormone- releasing hormone (LHRH) agonists, with or without androgens, may be included.
9. Patients not able to give an informed consent or comply with study regulations as deemed by study investigator.
10. Co-morbidity that, based on the assessment of the treating physician, may preclude the study treatment.
11. Pregnant or lactating patients.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall response rate (ORR), defined as partial or complete response as assessed by RECIST 1.1.

Secondary endpoints 4

1. Diseasefree survival and overall survival
2. Overall response rate defined as partial or complete response
3. Adverse event, serious adverse event and dose reductions or discontinuation due to toxicity.
4. Change from baseline in EORTC QLQ-C30 scores.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Kjetil Boye

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Kjetil Boye

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications