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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-21

Study Completion Date

2024-06-21

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Atezolizumab in Combination With Stereotactic Body Radiation Therapy (SBRT) and Surgery for Relapsed Osteosarcoma

NCT06492954

Osteosarcoma Pulmonary Recurrence of Osteosarcoma

RECRUITING PHASE1

Chemotherapy Plus Radiation Therapy Followed by Surgery in Treating Patients With Soft Tissue Sarcoma

NCT00002791

Sarcoma

COMPLETED PHASE2

Radiation Therapy Plus Doxorubicin in Treating Patients With Resectable Primary or Recurrent Retroperitoneal Soft Tissue Sarcoma

NCT00004123

Sarcoma

COMPLETED PHASE1

Combination Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Primary or Recurrent Sarcoma

NCT00017160

Stage III Adult Soft Tissue Sarcoma Recurrent Adult Soft Tissue Sarcoma Stage IVA Adult Soft Tissue Sarcoma +2 more

WITHDRAWN PHASE2

Combination Chemotherapy, Radiation Therapy, and Sargramostim Before and After Surgery in Treating Patients With Soft Tissue Sarcoma That Can Be Removed By Surgery

NCT00652860

Metastatic Cancer Sarcoma

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Soft Tissue Sarcoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment

Neoadjuvant Radiation plus Durvalumab and Tremelimumab Wide Surgical Resection Adjuvant Durvalumab

Group Type EXPERIMENTAL

Combination Radiation, Immunotherapy, Surgery

Intervention Type COMBINATION_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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Combination Radiation, Immunotherapy, Surgery

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.

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* 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.

Exclusion Criteria

* 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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No