Metastatic Adult Soft Tissue SarcomaPhase 2MEDISARCNCT03317457
Durvalumab and Tremelimumab Compared to Doxorubicin in Patients With Advanced or Metastatic Soft Tissue Sarcoma
A Phase 2 study testing Durvalumab and Tremelimumab and Doxorubicin in people with Metastatic Adult Soft Tissue Sarcoma and Recurrent Adult Soft Tissue Sarcoma, run by AIO-Studien-gGmbH at 1 site in Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Adult Soft Tissue Sarcoma, Recurrent Adult Soft Tissue Sarcoma
- What is being tested?
- Durvalumab and Tremelimumab and Doxorubicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteGermany
- Study dates
- 15 Dec 2017to 12 Aug 2022
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 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 2. Age ≥ 18 years at time of study entry 3. Body weight > 30kg at study inclusion 4. 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
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- 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:
- Uncertain differentiation (epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, malignant mesenchymoma, PEComa), chondrosarcoma, Ewing sarcomas/PNET, chordoma, malignant solitary fibrous tumors, embryonal rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma (low-grade), neuroblastoma, malignant mesothelioma, and mixed mesodermal tumors of the uterus (Study inclusion is based on local histopathological diagnosis). 5. Metastatic or locally advanced STS, not amendable to surgery with curative intention.
- 6. 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.
- 9. 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.
- 10. 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.
- 11. Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery and palliative radiotherapy for bone pain: 2 weeks) prior to start of treatment and patient recovered from toxic effects.
- 12. Adequate blood count, liver-enzymes, and renal function:
- Haemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
- Platelet count ≥ 100 x 109/L (>100,000 per mm3)
- Serum bilirubin ≤ 1.5 x ULN. This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
- Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance 13. Adequate cardiac function (left ventricular ejection fraction ≥50% as assessed by ECHO) 14. Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
- 15. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Who cannot join
- 1. 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].
- 6. 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.
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- 8. 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.
- 13. 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.
- 14. 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.
- 15. Any unresolved toxicity >CTCAE grade 2 from previous anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
- 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.
- 16. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 17. Known history of previous clinical diagnosis of tuberculosis 18. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab 19. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year) 20. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results 21. Participation in another clinical study with an investigational product during the last 30 days before inclusion 22. Any previous treatment with a PD-1 or PD-L1 or CTLA-4 inhibitor, including durvalumab and tremelimunab 23. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid 24. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug or ≤4 half-lifes of the agent administered, which ever comes first.
- 25. Previous enrollment or randomization in the present study (does not include screening failure).
- 26. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities (§ 40 Abs. 1 S. 3 Nr. 4 AMG).
- 27. 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].
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase II Study of Durvalumab (MEDI4736) and Tremelimumab Compared to Doxorubicin in Patients With Advanced or Metastatic Soft Tissue Sarcoma
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
- Being tested
- Durvalumab and Tremelimumab, Doxorubicin
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Durvalumab and TremelimumabBiological
immun checkpoint inhibitor
DoxorubicinDrug
Anthracycline
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Durvalumab and Tremelimumab |
| Doxorubicin | Active comparator | Doxorubicin 75 mg/qm q3wks for 6 courses Receives: Drug: Doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival (OS)
Measured: up to 57 months from randomization
Secondary outcomes (6)
AEs / SAEs and Treatment Emergent Adverse Events according to CTCAE 4.03
Assessment of adverse events of tremelimumab and durvalumab (MEDI4736) combination therapy
Measured: up to 18 months from randomization
Objective Response Rate (ORR) according to RECIST 1.1 criteria
Measured: up to 57months from randomization
OS mile stone rate at 24 months
Measured: up to 24 months from randomization
Duration of response
Measured: up to 57 months from randomization
progression-free survival (PFS)
Measured: up to 57 months from randomization
Quality of life QLQ-C30
scores according to EORTC QLQ-C30 scoring manual (Quality of life)
Measured: up to 12 months from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
15 Dec 201712 Aug 2022
- First posted23 Oct 2017
- Study start15 Dec 2017
- Primary completion12 Aug 2022
- Study completion12 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Adult Soft Tissue SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Treatment Arm A: Combination of Durvalumab and Tremelimumab Treatment Arm B: Doxorubicin
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- AIO-Studien-gGmbH
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Viktor Grünwald, Dr., Principal investigator, Universitätsklinikum Essen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03317457
- Sponsor's protocol ID
- AIO-STS-0415
- Other IDs
- 2016-004750-15, 2016
- Acronym
- MEDISARC
- Status last verified
- Jun 2023
- First submitted
- 18 Oct 2017
- Last updated
- 15 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No