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

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ClinicalTrials.gov Identifier: NCT03074318
Recruitment Status : Recruiting
First Posted : March 8, 2017
Last Update Posted : June 18, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

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 or cannot be removed by surgery. Monoclonal antibodies, such as avelumab, may block tumor growth in different ways by targeting certain cells. 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.

Condition or disease Intervention/treatment Phase
Metastatic Leiomyosarcoma Metastatic Liposarcoma Unresectable Leiomyosarcoma Unresectable Liposarcoma Drug: Avelumab Drug: Trabectedin Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of the combination of trabectedin and avelumab in patients with advanced leiomyosarcoma and liposarcomas (L-type sarcomas).

II. To assess the objective response rate of advanced L-type sarcoma patients receiving the combination of avelumab and trabectedin.

SECONDARY OBJECTIVES:

I. To explore the clinical activity of avelumab and trabectedin with respect to time to response.

II. To explore the clinical activity of avelumab and trabectedin with respect to duration of response.

III. To explore the clinical activity of avelumab and trabectedin with respect to progression-free survival (PFS) at 12 weeks.

IV. To explore the clinical activity of avelumab and trabectedin with respect to clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 weeks.

V. To explore the clinical activity of avelumab and trabectedin with respect to overall survival.

OUTLINE:

Patients receive avelumab intravenously (IV) over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive trabectedin IV over 24 hours on day 1. Courses repeat every 3 weeks and may repeat up to every 5 weeks after 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 2 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : April 15, 2019
Estimated Study Completion Date : September 15, 2020


Arm Intervention/treatment
Experimental: Treatment (avelumab, trabectedin)
Patients receive avelumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive trabectedin IV over 24 hours on day 1. Courses repeat every 3 weeks and may repeat up to every 5 weeks after 2 courses in the absence of disease progression or unacceptable toxicity.
Drug: Avelumab
Given IV
Other Names:
  • Bavencio
  • MSB-0010718C
  • MSB0010718C

Drug: Trabectedin
Given IV
Other Names:
  • Ecteinascidin
  • ecteinascidin 743
  • ET-743
  • Yondelis




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 30 days ]
    Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03.


Secondary Outcome Measures :
  1. Time to response [ Time Frame: Up to 2 years ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  2. Duration of response [ Time Frame: Up to 2 years ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  3. Progression-free survival (PFS) [ Time Frame: At 12 weeks ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  4. Complete response rate (CR) [ Time Frame: At 12 weeks ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  5. Partial response rate (PR) [ Time Frame: At 12 weeks ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  6. Stable disease (SD) [ Time Frame: At 12 weeks ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  7. Clinical benefit rate (percentage of patients who achieve CR+PR+SD) [ Time Frame: At 12 weeks ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.

  8. Overall survival [ Time Frame: Up to 2 years ]
    Assessed by Response Evaluation Criteria in Solid Tumors 1.1.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with advanced (metastatic or unresectable) leiomyosarcoma or liposarcoma
  • Being considered for trabectedin as standard of care
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL (may have been transfused)
  • Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN for all subjects
  • Creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula
  • Ejection fraction > 45%
  • Negative serum pregnancy test at screening for women of childbearing potential
  • Effective contraception for both male and female subjects if the risk of conception exists; women of childbearing potential and men able to father a child must agree to use a method of effective contraception; effective contraception is required throughout the study and for at least 1 month after avelumab treatment, 2 months after last dose of trabectedin for women of reproductive potential, and 5 months following the last dose of trabectedin for males with female partners of reproductive potential
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky performance scale >= 70

Exclusion Criteria:

  • All subjects with brain metastases, except those meeting the following criteria:

    • Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
    • No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
    • Subjects must be either off steroids or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent)
  • 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)
    • Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested positive)
  • 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, intro-ocular, 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] 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
  • Persisting toxicity related to prior therapy of grade > 1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy grade =< 2 is acceptable
  • Pregnancy or lactation
  • Known 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
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Any vaccination within 4 weeks of the first dose of avelumab, with the following exceptions:

    • Administration of inactivated vaccines, including inactivated flu vaccines, are allowable; however, they should not be given within 2 weeks prior to starting study treatment
  • Clinically significant cardiovascular disease including cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), congestive heart failure with New York Heart Association (NYHA) class II or greater or serious cardiac arrhythmia requiring medication
  • Severe (requiring active treatment) acute or chronic medical conditions including: colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis
  • Recent (within the past year) or active suicidal ideation or behavior

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03074318


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Seth M. Pollack    206-667-6629    spollack@fredhutch.org   
Principal Investigator: Seth M. Pollack         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Seth Pollack Fred Hutch/University of Washington Cancer Consortium

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03074318     History of Changes
Other Study ID Numbers: 9717
NCI-2017-00234 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9717 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: June 18, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leiomyosarcoma
Liposarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Adipose Tissue
Antibodies, Monoclonal
Trabectedin
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents