Durvalumab and Tremelimumab Compared to Doxorubicin in Patients With Advanced or Metastatic Soft Tissue Sarcoma

NCT03317457 | Completed Phase 2

• 2 other identifiers: AIO-STS-04152016-004750-15
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the trial is to assess the efficacy of Durvalumab and Tremelimumab in comparison to doxorubicin in treatment-naïve Soft tissue sarcoma patients

Conditions

Metastatic Adult Soft Tissue Sarcoma; Recurrent Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• overall survival (OS)

  up to 57 months from randomization

Secondary Outcomes (6)

• AEs / SAEs and Treatment Emergent Adverse Events according to CTCAE 4.03

  up to 18 months from randomization

• Objective Response Rate (ORR) according to RECIST 1.1 criteria

  up to 57months from randomization

• OS mile stone rate at 24 months

  up to 24 months from randomization

• Duration of response

  up to 57 months from randomization

• progression-free survival (PFS)

  up to 57 months from randomization

Study Arms (2)

Durvalumab and Tremelimumab

EXPERIMENTAL

Cycles/courses 1-3: Durvalumab 1.5g q4wks Tremelimumab 75 mg q4wks Cycles/courses ≥4: Durvalumab 1.5g q4wks Tremelimumab 75 mg q12wks

Biological: Durvalumab and Tremelimumab

Doxorubicin

ACTIVE COMPARATOR

Doxorubicin 75 mg/qm q3wks for 6 courses

Drug: Doxorubicin

Interventions

Durvalumab and Tremelimumab BIOLOGICAL

immun checkpoint inhibitor

Durvalumab and Tremelimumab

Doxorubicin DRUG

Anthracycline

Doxorubicin

Eligibility Criteria

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

You may qualify if:

• Fibrosarcoma
• Pleomorphic high grade sarcoma ("malignant fibrous histiocytoma")
• Leiomyosarcoma
• Liposarcoma (myxoid liposarcoma, dedifferentiated liposarcoma, pleomorphic liposarcoma)
• Malignant glomus tumor
• Rhabdomyosarcoma, alveolar or pleomorphic (excluding embryonal)
• Vascular sarcoma (angiosarcoma)
• Synovial sarcoma
• High-grade sarcoma, not otherwise specified (NOS)
• Malignant peripheral nerve sheath tumors
• Other types of sarcoma (not listed as ineligible), if approved by the coordinating investigator / study coordinator.
• Excluding:
• \. No prior treatment line for advanced or metastatic disease. 7. ECOG performance status 0-2 8. Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) are eligible.
• \. If prior palliative radiotherapy has been given to metastatic lesions: either ≥1 measurable lesion remains outside the radition field or the sole lesion meets RECIST 1.1 criteria for progression at study entry.
• \. Patients with bone lesions as the only measurable lesion are eligible, provided that lesions consist of soft tissue, which is measurable via CT or MRI.

You may not qualify if:

• \. Patients who are suitable for anthracycline-based combination therapies 2. Cardiac events such as arrhythmias, myocardial infarction, CHF, apoplexy, lung embolism within 6 months prior to study treatment 3. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's correction 4. Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 100 mmHg and systolic blood pressure \>160 mmHg) 5. Previous malignancy (other than STS) which either progresses or requires active treatment.
• Exceptions are: basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a or T1b prostate carcinoma, or superficial bladder tumor \[Ta, Tis and T1\].
• \. History or clinical evidence of CNS metastases
• Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria:
• are asymptomatic and
• have no requirement for steroids 6 weeks prior to start of study treament. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases 7. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• \. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) 9. History of primary immunodeficiency 10. History of allogeneic organ transplant 11. History of hypersensitivity to durvalumab, tremelimumab (alone or in combination), doxorubicin or any of the constituents of the products 12. Medication that is known to interfere with any of the agents applied in the trial.
• \. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
• \. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medication. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Coordinating Investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab (if applicable) may be included only after consultation with the Coordinating Investigator.
• \. Previous enrollment or randomization in the present study (does not include screening failure).
• \. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities (§ 40 Abs. 1 S. 3 Nr. 4 AMG).
• \. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts \[§ 40 Abs. 1 S. 3 Nr. 3a AMG\].

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• AstraZeneca: collaborator

Study Sites (1)

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

MeSH Terms

Conditions

Sarcoma

Interventions

durvalumab; tremelimumab; Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Viktor Grünwald, Dr.

  Universitätsklinikum Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment Arm A: Combination of Durvalumab and Tremelimumab Treatment Arm B: Doxorubicin

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 23, 2017
• Study Start: December 15, 2017
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2022
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)