AzTrials
AzTrials

Metastatic LeiomyosarcomaPhase 1/2NCT03074318

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

A Phase 1/2 study testing Avelumab and Trabectedin in people with Metastatic Leiomyosarcoma and Metastatic Liposarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Avelumab and Trabectedin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
28 Sep 2017to 15 Nov 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 23Show fewer
  • 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:
  • Females of child-bearing potential must agree to use highly effective contraception without interruption from initiation of therapy and while on study medication and have a negative serum pregnancy test (beta - human chorionic gonadotropin [hCG]) result at screening and agree to ongoing pregnancy testing during the course of the study, and at the end of study treatment; a highly effective method of contraception is defined as one that results in a low failure rate (that is, < 1% per year), when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner
  • Male subjects must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study
  • All ongoing toxicities related to prior therapies must be resolved to grade 1 or better (except alopecia)
  • Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky performance scale >= 70
  • Subjects must have one or more measurable lesions, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
  • Subjects must have a life expectancy of >= 6 months, as determined by the treating physician
  • Ability to understand and sign informed consent document
  • Willingness and ability to comply with the scheduled visits, laboratory tests, and other study procedures

Who cannot join

  • 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)
Show all 20Show fewer
  • 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
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase I/II Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of the combination of trabectedin and avelumab in subjects with advanced leiomyosarcoma and liposarcoma.

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

SECONDARY OBJECTIVE:

  1. To further explore the clinical activity and safety profile of avelumab and trabectedin as a combination therapy.

OUTLINE:

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.

After completion of study treatment, patients are followed up at 30 and 90 days, then every 12 weeks for 2 years.

Being tested
Avelumab, Trabectedin
Medical subject headings
Leiomyosarcoma, Liposarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    Also called Bavencio, MSB-0010718C, MSB0010718C

    Given IV

  • TrabectedinDrug

    Also called Ecteinascidin, ecteinascidin 743, ET-743, Yondelis

    Given IV

Study groups in NCT03074318
Study groupRoleWhat they receive
Phase 1 (1.5 mg/m^2 trabectedin + avelumab)ExperimentalAvelumab 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.
Receives: Drug: Avelumab; Drug: Trabectedin
Phase 1 (1.0 mg/m^2 trabectedin + avelumab)ExperimentalAvelumab 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.
Receives: Drug: Avelumab; Drug: Trabectedin
Phase 1 (1.2 mg/m^2 trabectedin + avelumab)ExperimentalAvelumab 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.
Receives: Drug: Avelumab; Drug: Trabectedin
Phase 2 (1.0 mg/m^2 trabectedin + avelumab)ExperimentalAvelumab 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.
Receives: Drug: Avelumab; Drug: Trabectedin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events

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

    Measured: up to 2 years 7 months total

  2. 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.

    Measured: Up to 2 years 7 months total

Secondary outcomes (9)

  1. Time to Response

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Time to response is defined as the amount of time from when the subject first received study treatment (Cycle 1, Day 1) to when they achieved a partial response on trial.

    With such small numbers, this data is not necessarily representative of what a larger study would report.

    Measured: Up to 2 years 7 months total

  2. Duration of Response

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Duration of response is defined as the amount of time a subject responded to study treatment with either a partial response or complete response until the date of last follow-up (if response ongoing at data cutoff) or the date until they progressed on study.

    Measured: Up to 2 years 7 months total

  3. Progression-free Survival (PFS)

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression is defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, appearance of new lesions while on study, or clear growth of a non-target lesion.

    Measured: At 12 weeks

  4. Complete Response Rate (CR)

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response is defined as disappearance of all evaluable disease.

    Measured: At 12 weeks

  5. Partial Response Rate (PR)

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Partial response is defined as a decrease in 30% or more in the sum of the longest diameter of target lesions.

    Measured: At 12 weeks

  6. Stable Disease (SD)

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Stable Disease is defined as neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD).

    Measured: At 12 weeks

  7. Clinical Benefit Rate

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical Benefit Rate is defined as the percentage of subjects who achieved a Complete Response (CR) + Partial Response (PR) + Stable Disease (SD).

    Measured: At 12 weeks

  8. Median Overall Survival (OS)

    Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

    Measured: Up to 2 years post End of Treatment, for a total of 3 years

  9. Adverse Event Profile - All Treatment-Related Grade 3-5 Adverse Events

    Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0

    Measured: Up to 2 years 7 months total

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2017
  2. Study start28 Sep 2017
  3. Primary completion15 Nov 2020
  4. Study completion15 Nov 2020

Why it stopped: Terminated due to PI leaving institution

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03074318
Sponsor's protocol ID
9717
Other IDs
NCI-2017-00234, 9717, P30CA015704, RG9217009
Status last verified
Apr 2022
First submitted
1 Mar 2017
Last updated
29 Apr 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Avelumab and Trabectedin in people with Metastatic Leiomyosarcoma and Metastatic Liposarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (time frame: up to 2 years 7 months total). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03074318.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in