Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Sarcoma

Death

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Tremelimumab

Immunologic Factors

Neoadjuvant Radiation plus Durvalumab and Tremelimumab Wide Surgical Resection Adjuvant Durvalumab

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.

Combination Radiation, Immunotherapy, Surgery

Vincent Y. Ng, MD

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.

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.

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

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

Number of subjects experiencing high-grade toxicity

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

Percentage of patients who have not died from soft tissue sarcoma

Percentage of patients who have not had a documented relapse of local or distant disease

Best overall response to Neoadjuvant Radiation and Immunotherapy using Response Evaluation Criteria in Solid Tumors (RECIST)

Best overall response to Neoadjuvant Radiation and Immunotherapy using immune-related response criteria (irRC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Durvalumab and Tremelimumab Plus Radiation for High Risk Soft-Tissue Sarcoma	NCT03116529	Soft Tissue Sar...	Combination Rad...	18 Years -	University of Maryland, Baltimore
Neoadjuvant Durvalumab and Tremelimumab Plus Radiation for High Risk Soft-Tissue Sarcoma	NCT03116529	Soft Tissue Sar...	Combination Rad...	18 Years -	University of Maryland, Baltimore

Spots Global Cancer Trial Database for combination radiation, immunotherapy, surgery