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Soft Tissue SarcomaPhase 1/2NEXISNCT03116529

Neoadjuvant Durvalumab and Tremelimumab Plus Radiation for High Risk Soft-Tissue Sarcoma

A Phase 1/2 study testing Combination Radiation, Immunotherapy, Surgery in people with Soft Tissue Sarcoma, run by University of Maryland, Baltimore at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Chemotherapy is controversial for soft tissue sarcoma that has not yet metastasized. Surgery and radiation are effective for local control, but there are no highly effective interventions to prevent metastatic spread of soft tissue sarcoma. Immunotherapy has shown promise in other types of cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Combination Radiation, Immunotherapy, Surgery
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
3 sitesUnited States
Study dates
21 Jun 2017to 21 Jun 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Written informed consent
  • Willingness and ability to comply with the protocol for the duration of the study
  • Histologically confirmed intermediate or high grade adult-type soft tissue sarcoma
  • Location of tumor is trunk (non-retroperitoneal) or extremities
  • Tumor at least 5 cm in greatest dimension and deep to fascia, or locally recurrent, or metastatic, or have had prior inadequate resections
  • Judged as at least marginally resectable
Show all 10Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Adequate normal organ and marrow function
  • Female subjects must be either of non-reproductive potential (i.e., 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.
  • Females of childbearing potential who are sexually active with a non-sterilized male partner and non-sterilized male subjects who are sexually active with a female partner of childbearing potential must be willing to use 2 methods of effective contraception from time of screening through 180 days after receipt of the final dose of Durvalumab + Tremelimumab combination therapy or 90 days after receipt of the final dose of Durvalumab Monotherapy, whichever is the longer time period.

Who cannot join

  • Primarily bone-based sarcomas that can occur in the soft tissue such as: extra-skeletal Ewing sarcoma, extra-skeletal osteosarcoma, peripheral chordoma, extra-skeletal myxoid chondrosarcoma, and mesenchymal chondrosarcoma
  • Predominantly low-grade soft tissue sarcoma, such as solitary fibrous tumor / hemangiopericytoma, well-differentiated liposarcoma, dermatofibrosarcoma protuberans, Kaposi's sarcoma
  • Pediatric-type soft tissue sarcoma, such as rhabdomyosarcoma
  • Gastrointestinal stromal tumors (GIST)
  • Retroperitoneal soft tissue sarcoma
  • Patients with extra-pulmonary metastases aside from lymph node involvement
Show all 46Show fewer
  • Surgically unresectable primary lesion
  • Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  • Any previous treatment with an anti-PD-1 (programmed cell death protein-1), anti-PD-L1 (programmed death ligand 1) or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy, including Durvalumab and Tremelimumab
  • History of hypersensitivity to Durvalumab or any excipient
  • History of hypersensitivity to Tremelimumab or any excipient
  • History of hypersensitivity to the combination or comparator agent
  • History or clinically confirmed pneumonitis or interstitial lung disease
  • Receipt of the last dose of anti-cancer therapy (cytotoxic chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 28 days prior to the first dose of study drug (28 days prior to the first dose of study drug for subjects who have received prior TKIs (tyrosine kinase inhibitors) [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C [If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required])
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, 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
  • Any unresolved toxicity (>grade 2) from previous anti-cancer therapy. NOTE: Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
  • Any prior immune-related adverse event (irAE) ≥ Grade 2 while receiving any previous immunotherapy agent, or any unresolved irAE > Grade 1
  • 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.
  • History of primary immunodeficiency
  • History of allogeneic organ transplant (e.g. solid organ/bone marrow transplant patients)
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infections
  • Cardiac conditions, such as:
  • symptomatic congestive heart failure
  • uncontrolled hypertension
  • unstable angina pectoris
  • cardiac arrhythmia
  • Active peptic ulcer disease or gastritis
  • History of inflammatory bowel disease, ulcerative colitis or Crohn's Disease
  • Active bleeding diatheses
  • Any subject known to have evidence of acute or chronic hepatitis B or hepatitis C
  • Any subject known to have evidence of human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)
  • Uncontrolled seizures
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
  • Known history of current or recent clinical diagnosis of tuberculosis (within three months prior to enrollment)
  • Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • Any signs or symptoms of bowel obstruction within 28 days prior to study entry
  • History of leptomeningeal carcinomatosis
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab, or active infection
  • History of psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
  • Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Previously enrolled in the present study
  • Participation in another clinical study with an investigational product during the last 6 months
  • Previously enrolled in the present study
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Maryland Medical Center, Greenebaum Comprehensive Cancer Center

    Baltimore, Maryland, 21201

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Arizona

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: Neoadjuvant Anti-PD-L1 (Durvalumab/MEDI4736) Plus Anti-CTLA-4 (Tremelimumab) and Radiation for High Risk Soft-Tissue Sarcoma

Chemotherapy is controversial for soft tissue sarcoma that has not yet metastasized. Surgery and radiation are effective for local control, but there are no highly effective interventions to prevent metastatic spread of soft tissue sarcoma. Immunotherapy has shown promise in other types of cancer. Combining two types of immunotherapy agents with preoperative radiation may help the immune system recognize the sarcoma and stimulate an anti-tumor immune response.

Read the detailed description

The main purposes of this study are to evaluate the safety, tolerability, and efficacy of Durvalumab and Tremelimumab in combination with radiation prior to surgical resection of high-risk soft tissue sarcoma in the pelvis and extremities.

Patients will receive the same radiation therapy and surgical care they would receive normally and with no change in timing or duration of each treatment. They will also receive two immunotherapy agents, Durvalumab and Tremelimumab, during radiation prior to surgery, and a single agent, Durvalumab, after surgery.

Being tested
Combination Radiation, Immunotherapy, Surgery
Keywords
Neoadjuvant, Soft Tissue Sarcoma, Immunotherapy, Checkpoint Inhibitor, PD-1 (Programmed Cell Death Protein 1), PD-L1 (Programmed Death Ligand 1), CTLA-4 (Cytotoxic T-Lymphocyte-Associated Protein 4), Radiotherapy, Durvalumab, Tremelimumab, Surgery, Radiation, Combined, Preoperative
Medical subject headings
Sarcoma, Parkinson Disease 4, Autosomal Dominant Lewy Body, Diabetes Mellitus, Insulin-Dependent, 12

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Combination Radiation, Immunotherapy, SurgeryCombination product

    Three doses of Durvalumab (1500 mg) and Tremelimumab (75 mg) given intravenously once every four weeks during radiotherapy prior to surgery.

    Radiation therapy delivered with a minimum dose of 50 Gy and 1.8-2 Gy per fraction. Bulky sarcomas, defined as >10 cms in greatest dimension, receive a single 15 Gy fraction of high-dose spatially fractionated (GRID) radiation therapy within 1-3 days prior to radiation therapy

    Surgical resection is performed at least 5-8 weeks after cessation of radiotherapy and 4 weeks after completion of neoadjuvant immunotherapy.

    Patients with no evidence of disease following surgical resection receive four additional doses and patients with evidence of disease receive nine additional doses of Durvalumab (1500 mg IV) once every four weeks unless there is clear progression of disease.

Study groups in NCT03116529
Study groupRoleWhat they receive
TreatmentExperimentalNeoadjuvant Radiation plus Durvalumab and Tremelimumab Wide Surgical Resection Adjuvant Durvalumab
Receives: Combination Product: Combination Radiation, Immunotherapy, Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity: Number of Subjects Experiencing High-grade Toxicity

    high-grade toxicity experienced during the course of the study

    Measured: 90 days after receipt of final dose of Durvalumab monotherapy or 180 days after receipt of final dose of combination Durvalumab/Tremelimumab, whichever is longer

  2. Histopathologic Response

    Number of subjects with an excellent response on histopathologic examination of the surgically removed tumor

    Measured: At time of surgery

Secondary outcomes (1)

  1. Overall Survival Rate

    Number of patients still alive

    Measured: Two years after start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2017
  2. Study start21 Jun 2017
  3. Primary completion21 Jun 2024
  4. Study completion21 Jun 2024

Why it stopped: Limited Accrual

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03116529
Sponsor's protocol ID
HP-00073356
Acronym
NEXIS
Status last verified
Apr 2026
First submitted
12 Apr 2017
Last updated
5 Nov 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Ng VY, Sahlani MN, Fogel JD, Chiu AK, Kallen ME, Davis D, Snider J, Regine W, Bentzen SM, Sausville E. Results of an Integrated Phase I/II Prospective Clinical Trial (NEXIS) for Neoadjuvant Anti-PD-L1 (Durvalumab) and Anti-CTLA-4 (Tremelimumab) With Radiation for High-Risk Soft-Tissue Sarcoma of the Trunk and Extremities. Cureus. 2024 Oct 22;16(10):e72119. doi: 10.7759/cureus.72119. eCollection 2024 Oct.

    PubMed 39575028

  • Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

    PubMed 32827353

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Combination Radiation, Immunotherapy, Surgery in people with Soft Tissue Sarcoma, run by University of Maryland, Baltimore at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity: Number of Subjects Experiencing High-grade Toxicity (time frame: 90 days after receipt of final dose of Durvalumab monotherapy or 180 days after receipt of final dose of combination Durvalumab/Tremelimumab, whichever is longer). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03116529, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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