Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes

NCT02815995 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2015-1071NCI-2016-01178
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if the combination of durvalumab and tremelimumab can help to control sarcoma. The safety of this drug combination will also be studied. This is an investigational study. Durvalumab and tremelimumab are not FDA approved or commercially available. They are currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work. Up to 150 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions

Advanced and/or Metastatic Sarcoma

Keywords

Malignant neoplasms of bone and articular cartilage; Multiple sarcoma subtypes; Advanced and/or metastatic sarcoma; Adipocytic tumors; Vascular tumors; Leiomyosarcoma; Angiosarcoma; Epithelioid hemangioendothelioma; Undifferentiated pleomorphic sarcoma; Synovial sarcoma; Osteosarcoma; Other sarcoma histologies; Durvalumab; Tremelimumab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20%increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  12 weeks

Secondary Outcomes (2)

• Tumor Response

  8 weeks, confirmatory scan at least 4 wks or later

• Overall Survival (OS)

  44 months

Study Arms (6)

Adipocytic Tumors Group

EXPERIMENTAL

Adipocytic Tumors Group consists of well-diff/de-differentiated, pleomorphic and myxoid LPS. Age group ≥12 and \<18: Dosages of study drugs to be determined (TBD). Age group ≥ 18: Durvalumab 1500 mg and Tremelimumab 75 mg every 4 weeks for 4 cycles followed by durvalumab 1500 mg every 4 weeks for up to 8 additional cycles. Combination of both agents administered every 4 weeks for a maximum of 4 doses, after which durvalumab continues as a single agent every 4 weeks till progression or unacceptable toxicity for a maximum of 8 additional doses.

Drug: Durvalumab; Drug: Tremelimumab

Vascular Tumors Group

EXPERIMENTAL

Vascular Tumors Group consists of leiomyosarcomas, angiosarcomas, epithelioid hemangioendotheliomas, and hemangiopericytomas. Age group ≥12 and \<18: Dosages of study drugs to be determined (TBD). Age group ≥ 18: Durvalumab1500 mg and Tremelimumab 75 mg every 4 weeks for 4 cycles followed by Durvalumab 1500 mg every 4 weeks for up to 8 additional cycles. Combination of both agents administered every 4 weeks for a maximum of 4 doses, after which durvalumab continues as a single agent every 4 weeks till progression or unacceptable toxicity for a maximum of 8 additional doses.

Drug: Durvalumab; Drug: Tremelimumab

Undifferentiated Pleomorphic Sarcoma Group

EXPERIMENTAL

Age group ≥12 and \<18: Dosages of study drugs to be determined (TBD). Age group ≥ 18: Durvalumab 1500 mg and Tremelimumab 75 mg every 4 weeks for 4 cycles followed by Durvalumab 1500 mg every 4 weeks for up to 8 additional cycles. Combination of both agents administered every 4 weeks for a maximum of 4 doses, after which durvalumab continues as a single agent every 4 weeks till progression or unacceptable toxicity for a maximum of 8 additional doses.

Drug: Durvalumab; Drug: Tremelimumab

Synovial Sarcoma Group

EXPERIMENTAL

Age group ≥12 and \<18: Dosages of study drugs to be determined (TBD). Age group ≥ 18: Durvalumab 1500 mg and Tremelimumab 75 mg every 4 weeks for 4 cycles followed by durvalumab 1500 mg every 4 weeks for up to 8 additional cycles. Combination of both agents administered every 4 weeks for a maximum of 4 doses, after which Durvalumab continues as a single agent every 4 weeks till progression or unacceptable toxicity for a maximum of 8 additional doses.

Drug: Durvalumab; Drug: Tremelimumab

Osteosarcoma Group

EXPERIMENTAL

Age group ≥12 and \<18: Dosages of study drugs to be determined (TBD). Age group ≥ 18: Durvalumab 1500 mg and Tremelimumab 75 mg every 4 weeks for 4 cycles followed by durvalumab 1500 mg every 4 weeks for up to 8 additional cycles. Combination of both agents administered every 4 weeks for a maximum of 4 doses, after which Durvalumab continues as a single agent every 4 weeks till progression or unacceptable toxicity for a maximum of 8 additional doses.

Drug: Durvalumab; Drug: Tremelimumab

Other Sarcomas Group

EXPERIMENTAL

Age group ≥12 and \<18: Dosages of study drugs to be determined (TBD). Age group ≥ 18: Durvalumab 1500 mg and Tremelimumab 75 mg every 4 weeks for 4 cycles followed by durvalumab 1500 mg every 4 weeks for up to 8 additional cycles. Combination of both agents administered every 4 weeks for a maximum of 4 doses, after which Durvalumab continues as a single agent every 4 weeks till progression or unacceptable toxicity for a maximum of 8 additional doses.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

Age group ≥ 18: Durvalumab 1500 mg by vein every 4 weeks for 4 cycles. After Week 16, participant may continue to receive durvalumab alone by vein for an additional 32 weeks (8 doses).

Adipocytic Tumors Group; Osteosarcoma Group; Other Sarcomas Group; Synovial Sarcoma Group; Undifferentiated Pleomorphic Sarcoma Group; Vascular Tumors Group

Tremelimumab DRUG

Age group ≥ 18: Tremelimumab 75 mg every 4 weeks for 4 cycles.

Adipocytic Tumors Group; Osteosarcoma Group; Other Sarcomas Group; Synovial Sarcoma Group; Undifferentiated Pleomorphic Sarcoma Group; Vascular Tumors Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: \>/= 18 years of age
• Histologically or cytologically confirmed sarcoma that fall into one of the following categories Patients with low-grade tumors are eligible if there is definite evidence of metastasis or progression (defined as at least a 10% increase in the cumulative sum of the longest diameters within a 3 month period): 1. Adipocytic tumors (Well-differentiated/dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma) 2. Vascular tumors (leiomyosarcoma, angiosarcoma) 3. Undifferentiated pleomorphic sarcoma 4. Synovial sarcoma 5. Osteosarcoma 6. Other sarcoma histologies
• Must have received and have progressed, are refractory or intolerant to standard therapy appropriate for the specific sarcoma subtype, if there is a standard therapy for the subtype (i.e. Progressing well-differentiated liposarcoma, clear cell sarcoma etc do not require prior therapy).
• Subjects must have at least 1 lesion that is measurable by irRECIST a. A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per irRECIST, and has clearly progressed. b. Subjects undergoing fresh tumor biopsies must have additional non-target lesions that can be biopsied at acceptable risk as judged by the investigator or if no other lesion suitable for biopsy, then an irRECIST target lesion used for biopsy must be \>/= 2 cm in longest diameter.
• Subjects must consent to provide archived tumor specimens for correlative biomarker studies. Tumor tissue must be identified and availability confirmed prior to initiation of study therapy. In the setting where archival material is unavailable or unsuitable for use, or there have been multiple intervening therapies subjects must consent and undergo fresh tumor biopsy. A tumor lesion planned for biopsy must not be an irRECIST target lesion unless there are no other lesions suitable for biopsy and lesion used for biopsy is \>/= 2 cm in longest diameter.
• ECOG performance status of 0 or 1
• Adequate organ function as determined by (lymphocyte count): a. Hematological (without growth factor or transfusion support): i. Absolute neutrophil count \>/= 1.5 x 10\^9/L (1,500/mm\^3) ii. Platelet count \>/= 90 × 10\^9/L (100,000/mm\^3) iii. Hemoglobin \>/= 8.0 g/dL within first 2 weeks prior to first dose of investigational product b. Renal: i. Calculated creatinine clearance (CrCl) or 24-hour urine CrCl \> 50 mL/min Cockcroft-Gault formula (using actual body weight) will be used to calculate CrCl, except for pts with Osteosarcoma who will be allowed to participate with an estimated creatinine clearance (CrCl) of \> 40 mL/min, as calculated by the Cockcroft-Gault equation. c. Hepatic: i. Total bilirubin \</= 1.5 × ULN; for subjects with documented/suspected Gilbert's disease, bilirubin \</= 3 × ULN ii. AST and ALT \</= 2.5 × ULN; for subjects hepatic metastases, ALT and AST \</= 5 × ULN
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product.
• Life expectancy of at least 6 months.
• Ability to understand the purposes and risks of the study and has signed a written consent form approved by the investigator's IRB/Ethics Committee

You may not qualify if:

• Prior therapy with anti-PD1, anti-PD-L1 or anti-CTLA-4 antibody
• Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression. Subjects previously treated central nervous system metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management for at least 14 days prior to first dose of MEDI4736 and tremelimumab are permitted to enroll.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
• Receipt of any conventional or investigational anticancer therapy not otherwise specified above within 28 days or 5 half-lives of the agent prior to the first dose of durvalumab and tremelimumab.
• Any concurrent chemotherapy, Immunotherapies or biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. In addition, local treatment (eg, by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable beyond the first cycle with prior consultation and in agreement with the PI.
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI4736 or tremelimumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection), b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent, c. Steroids as premedication for hypersensitivity reactions (eg, computed tomography \[CT\] scan premedication).
• History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis
• True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C.
• Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products (NOTE: Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of investigational products).
• Major surgery (as defined by the investigator) within 4 weeks or thoracotomy for pulmonary metastases within 2 weeks prior to first dose of treatment or if still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable.
• Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.
• 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, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from MEDI4736 or tremelimumab, or compromise the ability of the subject to give written informed consent.
• Any condition that, in the opinion of the investigator or sponsor, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
• Patients with a history of pneumonitis or interstitial lung disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• MedImmune LLC: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Somaiah N, Conley AP, Parra ER, Lin H, Amini B, Solis Soto L, Salazar R, Barreto C, Chen H, Gite S, Haymaker C, Nassif EF, Bernatchez C, Mitra A, Livingston JA, Ravi V, Araujo DM, Benjamin R, Patel S, Zarzour MA, Sabir S, Lazar AJ, Wang WL, Daw NC, Zhou X, Roland CL, Cooper ZA, Rodriguez-Canales J, Futreal A, Soria JC, Wistuba II, Hwu P. Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Lancet Oncol. 2022 Sep;23(9):1156-1166. doi: 10.1016/S1470-2045(22)00392-8. Epub 2022 Aug 4.

  PMID: 35934010 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Vascular Neoplasms; Leiomyosarcoma; Hemangiosarcoma; Hemangioendothelioma, Epithelioid; Histiocytoma, Malignant Fibrous; Sarcoma, Synovial; Osteosarcoma

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Soft Tissue Neoplasms; Neoplasms by Site; Neoplasms; Vascular Diseases; Cardiovascular Diseases; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Vascular Tissue; Hemangioendothelioma; Hemangioma; Histiocytoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Bone Tissue

Results Point of Contact

• Title: Dr. Neeta Somaiah
• Organization: The University of Texas MD Anderson Cancer Center

nsomaiah@mdanderson.org

(713) 792-3626

Study Officials

• Neeta Somaiah, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: June 28, 2016
• Study Start: August 16, 2016
• Primary Completion: June 17, 2024
• Study Completion: June 17, 2024
• Last Updated: June 12, 2025
• Results First Posted: June 12, 2025

Record last verified: 2025-02

Locations

US (1)