Sequential Neoadjuvant Chemotherapy in Soft Tissue Sarcoma

NCT04776525 | Recruiting Phase 2

• 1 other identifier: 44-2020
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

Nearly half of patients with high-grade, localized soft tissue sarcoma (STS) of extremities and trunk wall develop disease recurrence after local therapy. Adjuvant chemotherapy with ifosfamide and doxorubicin may improve long-term disease-free survival, but the benefit of adjuvant treatment is limited and predictive factors for treatment response are lacking. The aim of this study is to explore sequential treatment with ifosfamide and doxorubicin in a neoadjuvant setting and to investigate biomarkers predictive of treatment response.

Conditions

Soft Tissue Sarcoma

Keywords

Doxorubicin; Ifosfamide; Sarcoma; Neoadjuvant; Sequential

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Partial or complete response using RECIST v1.1

  Up to 16 weeks

Secondary Outcomes (2)

• Incidence of treatment-related adverse events as assessed by CTCAE v5.0 and dose reductions (safety and tolerability)

  Until 30 days after last dose of study treatment

• Correlation between TP53 mutation assessed by sequencing of tumor DNA and overall response

  Up to 16 weeks

Other Outcomes (4)

• Disease-free survival

  Up to 10 years after completion of study treatment

• Overall survival

  Up to 10 years after completion of study treatment

• Health-related quality of life

  Up to 10 years after completion of study treatment

Study Arms (1)

Sequential ifosfamide and doxorubicin

EXPERIMENTAL

Four cycles ifosfamide 9 g/m2 and four cycles doxorubicin 80 mg/m2. Each cycle has a duration of 14 days.

Drug: Ifosfamide; Drug: Doxorubicin

Interventions

Ifosfamide DRUG

3 g/m2 each day for three days

Also known as: Holoxan

Sequential ifosfamide and doxorubicin

Doxorubicin DRUG

80 mg/m2 over four hours day 1

Also known as: Adriamycin

Sequential ifosfamide and doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age at the time of informed consent.
• Histological diagnosis of soft tissue sarcoma belonging to one of the following histotypes:
• Leiomyosarcoma
• Malignant peripheral nerve sheath tumor
• Undifferentiated pleomorphic sarcoma
• Myxofibrosarcoma
• Synovial sarcoma
• Pleomorphic liposarcoma
• Pleomorphic rhabdomyosarcoma
• Unclassified spindle cell sarcoma
• Malignancy grade ≥ 2 according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system.
• Tumor localized in extremity, girdle and/or trunk wall.
• Primary tumor size ≥5.0 cm as measured in the longest diameter on diagnostic MRI or CT scan.
• Primary tumor location below the superficial fascia or involving the superficial fascia, i.e. deep-seated according to the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone (4th edition, 2013).
• Patients must have a measurable tumor according to RECIST v1.1.

You may not qualify if:

• Any prior therapy for soft tissue sarcoma.
• 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.
• Urinary obstruction.
• Known hypersensitivity towards ifosfamide, doxorubicin or pegfilgrastim, their metabolites and other ingredients in the drug administration formulation.
• 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.
• Left ventricular ejection fraction (LVEF) \< 50%.
• 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 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.
• Patients not able to give an informed consent or comply with study regulations as deemed by study investigator.
• Any other significant comorbidities, such as active infection, uncontrolled pulmonary or liver disease, active cystitis, or any other condition, that based on the assessment of the treating physician could compromise compliance with the protocol or predispose the patient to safety risks.
• Pregnant or lactating patients.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Haukeland University Hospital: collaborator

Study Sites (2)

Haukeland University Hospital

Bergen, Norway

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Ifosfamide; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Kjetil Boye, MD PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kjetil Boye, MD PhD

CONTACT

+4722934000; kjetil.boye@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: March 1, 2021
• Study Start: April 27, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2036
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2)