A Randomized Phase II Study of Durvalumab (MEDI4736) and Tremelimumab Compared to Doxorubicin in Patients With Advanced or Metastatic Soft Tissue Sarcoma

AIO-Studien-gGmbH1 site in 1 country103 target enrollmentDecember 15, 2017

ConditionsMetastatic Adult Soft Tissue Sarcoma Recurrent Adult Soft Tissue Sarcoma

InterventionsDurvalumab and Tremelimumab Doxorubicin

DrugsDoxorubicin

Overview

Phase: Phase 2
Intervention: Durvalumab and Tremelimumab
Conditions: Metastatic Adult Soft Tissue Sarcoma
Sponsor: AIO-Studien-gGmbH
Enrollment: 103
Locations: 1
Primary Endpoint: overall survival (OS)
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

December 15, 2017

End Date

August 12, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AIO-Studien-gGmbH

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
•Age ≥ 18 years at time of study entry
•Body weight \> 30kg at study inclusion
•Histologically confirmed diagnosis of metastatic or advanced soft tissue sarcoma of intermediate or high grade \[according to FNCLCC score; intermediate=grade 2 score of 4-5 points, high grade = grade 3 score of 6-8 points\] with disease progression within 6 months prior to study inclusion:
•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)

Exclusion Criteria

•Patients who are suitable for anthracycline-based combination therapies
•Cardiac events such as arrhythmias, myocardial infarction, CHF, apoplexy, lung embolism within 6 months prior to study treatment
•Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's correction
•Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 100 mmHg and systolic blood pressure \>160 mmHg)
•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

Arms & Interventions

Durvalumab and Tremelimumab

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

Intervention: Durvalumab and Tremelimumab

Doxorubicin

Doxorubicin 75 mg/qm q3wks for 6 courses

Intervention: Doxorubicin

Outcomes

Primary Outcomes

overall survival (OS)

Time Frame: up to 57 months from randomization

Secondary Outcomes

AEs / SAEs and Treatment Emergent Adverse Events according to CTCAE 4.03(up to 18 months from randomization)
Duration of response(up to 57 months from randomization)
Objective Response Rate (ORR) according to RECIST 1.1 criteria(up to 57months from randomization)
Quality of life QLQ-C30(up to 12 months from randomization)
OS mile stone rate at 24 months(up to 24 months from randomization)
progression-free survival (PFS)(up to 57 months from randomization)