Avelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery

NCT03074318 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: 9717NCI-2017-00234P30CA015704RG9217009
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II studies the side effects of avelumab and trabectedin and how well they work in treating patients with leiomyosarcoma or liposarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab and trabectedin may work better in treating patients with liposarcoma or leiomyosarcoma.

Conditions

Metastatic Leiomyosarcoma; Metastatic Liposarcoma; Unresectable Leiomyosarcoma; Unresectable Liposarcoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

  up to 2 years 7 months total

• Overall Response Rate (ORR)

  Rate of Partial Response (PR) + Complete Response (CR), which is the best response for each subject determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for target lesions and assessed by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan. Partial response is defined as a decrease in 30% or more in the sum of the longest diameter of target lesions, and complete response is defined as disappearance of all evaluable disease. No subjects had a complete response on this study so the ORR represents subjects who had a partial response only.

  Up to 2 years 7 months total

Secondary Outcomes (9)

• Time to Response

  Up to 2 years 7 months total

• Duration of Response

  Up to 2 years 7 months total

• Progression-free Survival (PFS)

  At 12 weeks

• Complete Response Rate (CR)

  At 12 weeks

• Partial Response Rate (PR)

  At 12 weeks

Study Arms (4)

Phase 1 (1.5 mg/m^2 trabectedin + avelumab)

EXPERIMENTAL

Avelumab will be administered every 2 weeks. Trabectedin will be administered every 3 weeks for the first two doses (Week 1 and Week 4), and then every four weeks (Week 7, Week 11,…) moving forward. After Cycle 2 of trabectedin, dosing may extend to every 5 weeks at investigator discretion, for management of trabectedin-associated toxicity only. Delays of trabectedin beyond 5 weeks may be allowed but require written approval from the Sponsor-Investigator. On days where both drugs are scheduled to be administered, avelumab will be administered first. This will continue until unacceptable toxicity or confirmed disease progression.

Drug: Avelumab; Drug: Trabectedin

Phase 1 (1.0 mg/m^2 trabectedin + avelumab)

EXPERIMENTAL

Avelumab will be administered every 2 weeks. Trabectedin will be administered every 3 weeks for the first two doses (Week 1 and Week 4), and then every four weeks (Week 7, Week 11,…) moving forward. After Cycle 2 of trabectedin, dosing may extend to every 5 weeks at investigator discretion, for management of trabectedin-associated toxicity only. Delays of trabectedin beyond 5 weeks may be allowed but require written approval from the Sponsor-Investigator. On days where both drugs are scheduled to be administered, avelumab will be administered first. This will continue until unacceptable toxicity or confirmed disease progression.

Drug: Avelumab; Drug: Trabectedin

Phase 1 (1.2 mg/m^2 trabectedin + avelumab)

EXPERIMENTAL

Avelumab will be administered every 2 weeks. Trabectedin will be administered every 3 weeks for the first two doses (Week 1 and Week 4), and then every four weeks (Week 7, Week 11,…) moving forward. After Cycle 2 of trabectedin, dosing may extend to every 5 weeks at investigator discretion, for management of trabectedin-associated toxicity only. Delays of trabectedin beyond 5 weeks may be allowed but require written approval from the Sponsor-Investigator. On days where both drugs are scheduled to be administered, avelumab will be administered first. This will continue until unacceptable toxicity or confirmed disease progression.

Drug: Avelumab; Drug: Trabectedin

Phase 2 (1.0 mg/m^2 trabectedin + avelumab)

EXPERIMENTAL

Avelumab will be administered every 2 weeks. Trabectedin will be administered every 3 weeks for the first two doses (Week 1 and Week 4), and then every four weeks (Week 7, Week 11,…) moving forward. After Cycle 2 of trabectedin, dosing may extend to every 5 weeks at investigator discretion, for management of trabectedin-associated toxicity only. Delays of trabectedin beyond 5 weeks may be allowed but require written approval from the Sponsor-Investigator. On days where both drugs are scheduled to be administered, avelumab will be administered first. This will continue until unacceptable toxicity or confirmed disease progression.

Drug: Avelumab; Drug: Trabectedin

Interventions

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Phase 1 (1.0 mg/m^2 trabectedin + avelumab); Phase 1 (1.2 mg/m^2 trabectedin + avelumab); Phase 1 (1.5 mg/m^2 trabectedin + avelumab); Phase 2 (1.0 mg/m^2 trabectedin + avelumab)

Trabectedin DRUG

Given IV

Also known as: Ecteinascidin, ecteinascidin 743, ET-743, Yondelis

Phase 1 (1.0 mg/m^2 trabectedin + avelumab); Phase 1 (1.2 mg/m^2 trabectedin + avelumab); Phase 1 (1.5 mg/m^2 trabectedin + avelumab); Phase 2 (1.0 mg/m^2 trabectedin + avelumab)

Eligibility Criteria

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

You may qualify if:

• Must have a histologically confirmed diagnosis of advanced (metastatic or unresectable) soft tissue sarcoma with one of the following subtypes:
• Leiomyosarcoma
• Liposarcoma
• Subject must be clinically indicated to receive trabectedin therapy as part of routine care. Subjects may be first line, or have received any number of prior systemic therapies
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) mg/dL
• Aspartate aminotransferase (AST) =\< 2.5 x ULN and alanine aminotransferase (ALT) =\< 2.5 x ULN
• Alkaline phosphatase \< 2.5 x ULN
• Serum creatinine =\< 1.5 x ULN
• Calculated creatinine clearance \>= 30 mL/min using the Cockcroft-Gault formula may be included
• Creatinine phosphokinase (CPK) =\< 2.5 x ULN
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L)
• Hemoglobin \>= 9 g/dL
• Subject must demonstrate a left ventricular ejection fraction (LVEF) \> 45% by echocardiography (ECHO) or multigated acquisition scan (MUGA)
• Male or non-pregnant and non-breast feeding female:

You may not qualify if:

• Known active, uncontrolled, or symptomatic central nervous system (CNS) metastases; a subject with controlled and asymptomatic CNS metastases may participate in this study; as such, the subject must have completed any prior treatment for CNS metastases \>= 28 days (including radiotherapy and/or surgery) prior to the start of treatment in this study and should not be receiving chronic corticosteroid therapy in excess of 10 mg daily prednisone (or equivalent) for CNS metastases; subjects with known CNS metastases must be confirmed radiographically stable by at least one imaging study, at least 28 days from last treatment
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 2 weeks of enrollment
• Prior organ transplantation, including allogeneic stem cell transplantation
• Prior treatment with trabectedin
• Significant acute or chronic infections including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Known active infection with hepatitis B or hepatitis C
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
• Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses =\< 10 mg or 10 mg equivalent prednisone per day
• Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, introocular, or inhalation) are acceptable
• Known severe hypersensitivity reactions to monoclonal antibodies (grade \>= 3 National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Pregnant or lactating females
• Known, active alcohol or drug abuse
• All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• EMD Serono: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leiomyosarcoma; Liposarcoma

Interventions

avelumab; Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Seth Pollack, MD, Director of Sarcoma Program
• Organization: Northwestern University

seth.pollack@northwestern.edu

312-503-5320

Study Officials

• Seth Pollack

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine (Hematology and Oncology)

Model Details: Subjects were enrolled into Phase 1, first into 1.5 mg/m\^2 trabectedin dose, then 1.0 mg/m\^2 trabectedin, then 1.2 mg/m\^2 trabectedin. Once the recommended Phase 2 dose was selected at 1.0 mg/m\^2 trabectedin, all subsequent subjects were enrolled into Phase 2.

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 8, 2017
• Study Start: September 28, 2017
• Primary Completion: November 15, 2020
• Study Completion: November 15, 2020
• Last Updated: April 29, 2022
• Results First Posted: April 29, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)