Avelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery
Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT03074318
Collaborator
National Cancer Institute (NCI) (NIH), EMD Serono (Industry)
35
1
4
37.6
0.9
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To assess the safety and tolerability of the combination of trabectedin and avelumab in subjects with advanced leiomyosarcoma and liposarcoma.
-
To assess the objective response rate of advanced L-type sarcoma patients receiving the combination regimen of avelumab and trabectedin.
SECONDARY OBJECTIVE:
- 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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
35 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention 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.Subjects were enrolled into Phase 1, first into 1.5 mg/m2 trabectedin dose, then 1.0 mg/m2 trabectedin, then 1.2 mg/m2 trabectedin. Once the recommended Phase 2 dose was selected at 1.0 mg/m2 trabectedin, all subsequent subjects were enrolled into Phase 2.
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
:
Sep 28, 2017
Actual Primary Completion Date
:
Nov 15, 2020
Actual Study Completion Date
:
Nov 15, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1 (1.5 mg/m^2 trabectedin + avelumab) 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
Given IV
Other Names:
Drug: Trabectedin
Given IV
Other Names:
|
| Experimental: Phase 1 (1.0 mg/m^2 trabectedin + avelumab) 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
Given IV
Other Names:
Drug: Trabectedin
Given IV
Other Names:
|
| Experimental: Phase 1 (1.2 mg/m^2 trabectedin + avelumab) 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
Given IV
Other Names:
Drug: Trabectedin
Given IV
Other Names:
|
| Experimental: Phase 2 (1.0 mg/m^2 trabectedin + avelumab) 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
Given IV
Other Names:
Drug: Trabectedin
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Incidence of Adverse Events [up to 2 years 7 months total]
Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
- Overall Response Rate (ORR) [Up to 2 years 7 months total]
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.
Secondary Outcome Measures
- Time to Response [Up to 2 years 7 months total]
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.
- Duration of Response [Up to 2 years 7 months total]
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.
- Progression-free Survival (PFS) [At 12 weeks]
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.
- Complete Response Rate (CR) [At 12 weeks]
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response is defined as disappearance of all evaluable disease.
- Partial Response Rate (PR) [At 12 weeks]
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.
- Stable Disease (SD) [At 12 weeks]
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).
- Clinical Benefit Rate [At 12 weeks]
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).
- Median Overall Survival (OS) [Up to 2 years post End of Treatment, for a total of 3 years]
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Adverse Event Profile - All Treatment-Related Grade 3-5 Adverse Events [Up to 2 years 7 months total]
Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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/mm3 (100 x 109/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
Exclusion Criteria:
-
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
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Fred Hutchinson Cancer Center
- National Cancer Institute (NCI)
- EMD Serono
Investigators
- Principal Investigator: Seth Pollack, Northwestern University
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Seth Pollack,
Associate Professor of Medicine (Hematology and Oncology),
Northwestern University
ClinicalTrials.gov Identifier:
NCT03074318
Other Study ID Numbers:
- 9717
- NCI-2017-00234
- 9717
- P30CA015704
- RG9217009
First Posted:
Mar 8, 2017
Last Update Posted:
Apr 29, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase 1 Dose Level 1 | Phase 1 Dose Level 2 | Phase 1 Dose Level 3 | Phase 2 |
|---|---|---|---|---|
| Arm/Group Description | Subjects received 1.5 mg/m^2 of trabectedin plus avelumab. | Subjects received 1.0 mg/m^2 of trabectedin plus avelumab | Subjects received 1.2 mg/m^2 of trabectedin plus avelumab. | Subjects received 1.0 mg/m^2 trabectedin plus avelumab. |
| Period Title: Overall Study | ||||
| STARTED | 6 | 7 | 6 | 16 |
| COMPLETED | 2 | 2 | 0 | 0 |
| NOT COMPLETED | 4 | 5 | 6 | 16 |
Baseline Characteristics
| Arm/Group Title | Phase 1 (1.5 mg/m^2 Trabectedin) | Phase 1 (1.0 mg/m^2 Trabectedin) | Phase 1 (1.2 mg/m^2 Trabectedin) | Phase 2 (Avelumab, Trabectedin) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Phase 1: 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. Avelumab: Given IV Trabectedin: Given IV | Phase 1: 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. Avelumab: Given IV Trabectedin: Given IV | Phase 1: 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. Avelumab: Given IV Trabectedin: Given IV | Phase 2: 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. Avelumab: Given IV Trabectedin: Given IV | Total of all reporting groups |
| Overall Participants | 6 | 7 | 6 | 16 | 35 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
4
66.7%
|
7
100%
|
4
66.7%
|
7
43.8%
|
22
62.9%
|
| >=65 years |
2
33.3%
|
0
0%
|
2
33.3%
|
9
56.3%
|
13
37.1%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
1
16.7%
|
5
71.4%
|
3
50%
|
11
68.8%
|
20
57.1%
|
| Male |
5
83.3%
|
2
28.6%
|
3
50%
|
5
31.3%
|
15
42.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
6
100%
|
7
100%
|
6
100%
|
14
87.5%
|
33
94.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
2
12.5%
|
2
5.7%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
1
14.3%
|
0
0%
|
1
6.3%
|
2
5.7%
|
| Asian |
0
0%
|
1
14.3%
|
1
16.7%
|
2
12.5%
|
4
11.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
6
100%
|
4
57.1%
|
5
83.3%
|
12
75%
|
27
77.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
14.3%
|
0
0%
|
1
6.3%
|
2
5.7%
|
| Type of Sarcoma (Count of Participants) | |||||
| Uterine Leiomyosarcoma |
0
0%
|
3
42.9%
|
0
0%
|
3
18.8%
|
6
17.1%
|
| Non-Uterine Leiomyosarcoma |
4
66.7%
|
2
28.6%
|
2
33.3%
|
10
62.5%
|
18
51.4%
|
| Dedifferentiated Liposarcoma |
2
33.3%
|
1
14.3%
|
3
50%
|
3
18.8%
|
9
25.7%
|
| Myxoid/Round Cell Liposarcoma |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
1
2.9%
|
| Pleomorphic Liposarcoma |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
2.9%
|
| Lines of Prior Therapy (Count of Participants) | |||||
| 0 Lines of Prior Therapy |
2
33.3%
|
0
0%
|
0
0%
|
3
18.8%
|
5
14.3%
|
| 1 Line of Prior Therapy |
1
16.7%
|
1
14.3%
|
2
33.3%
|
8
50%
|
12
34.3%
|
| 2 Lines of Prior Therapy |
2
33.3%
|
0
0%
|
2
33.3%
|
3
18.8%
|
7
20%
|
| 3 Lines of Prior Therapy |
1
16.7%
|
1
14.3%
|
2
33.3%
|
1
6.3%
|
5
14.3%
|
| 4 Lines of Prior Therapy |
0
0%
|
4
57.1%
|
0
0%
|
0
0%
|
4
11.4%
|
| 5 Lines of Prior Therapy |
0
0%
|
1
14.3%
|
0
0%
|
1
6.3%
|
2
5.7%
|
Outcome Measures
| Title | Incidence of Adverse Events |
|---|---|
| Description | Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. |
| Time Frame | up to 2 years 7 months total |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cumulative number of adverse events experienced on trial by all patients, reported per grade. |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | Subjects received 1.5 mg/m2 of trabectedin plus avelumab. | Subjects received 1.0 mg/m^2 trabectedin plus avelumab. | Subjects received 1.2 mg/m^2 trabectedin plus avelumab. | Subjects received 1.0 mg/m^2 trabectedin plus avelumab. |
| Measure Participants | 6 | 7 | 6 | 16 |
| Grade 1 |
95
|
98
|
86
|
201
|
| Grade 2 |
41
|
46
|
33
|
115
|
| Grade 3 |
12
|
14
|
9
|
40
|
| Grade 4 |
2
|
0
|
0
|
6
|
| Grade 5 |
1
|
0
|
0
|
0
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | Up to 2 years 7 months total |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects enrolled in Phase 2 plus subjects treated at the Recommended Phase 2 Dose (RP2D). |
| Arm/Group Title | Treatment (Avelumab, Trabectedin) |
|---|---|
| Arm/Group Description | Subjects enrolled in Phase 2 plus subjects treated at the Recommended Phase 2 dose. |
| Measure Participants | 23 |
| Number [percentage of participants] |
13
216.7%
|
| Title | Time to Response |
|---|---|
| Description | 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. |
| Time Frame | Up to 2 years 7 months total |
Outcome Measure Data
| Analysis Population Description |
|---|
| Average time to response for the 4 subjects who responded in both Phase 1 and Phase 2. Only subjects who had a response to treatment are included in this analysis. |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 1 | 0 | 0 | 3 |
| Mean (Full Range) [days] |
158
|
189
|
| Title | Duration of Response |
|---|---|
| Description | 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. |
| Time Frame | Up to 2 years 7 months total |
Outcome Measure Data
| Analysis Population Description |
|---|
| Average duration of response for the 4 subjects who responded to treatment in both Phase 1 and Phase 2. Only subjects who had a response to treatment are included in this analysis. |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 1 | 0 | 0 | 3 |
| Mean (Full Range) [days] |
NA
|
NA
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | At 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects treated in Phase 1 and Phase 2 evaluated at 3 months. NOTE: one subject was not evaluable for response and was replaced after withdrawing from study before response evaluation. |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 6 | 6 | 6 | 16 |
| Number [percentage of participants] |
50
833.3%
|
50
714.3%
|
83
1383.3%
|
63
393.8%
|
| Title | Complete Response Rate (CR) |
|---|---|
| Description | Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response is defined as disappearance of all evaluable disease. |
| Time Frame | At 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| NOTE: one subject was not evaluable for response and was replaced after withdrawing from study before response evaluation. |
| Arm/Group Title | Phase 1, 1.5 mg/m^2 Trabectedin | Phase 1, 1.0 mg/m^2 Trabectedin | Phase 1, 1.2 mg/m^2 Trabectedin | Phase 2, 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 6 | 6 | 6 | 16 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Partial Response Rate (PR) |
|---|---|
| Description | 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. |
| Time Frame | At 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| NOTE: One subject was not evaluable for response and was replaced after withdrawing from the study before response evaluation. |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 6 | 6 | 6 | 16 |
| Count of Participants [Participants] |
1
16.7%
|
0
0%
|
0
0%
|
3
18.8%
|
| Title | Stable Disease (SD) |
|---|---|
| Description | 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). |
| Time Frame | At 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| NOTE: one subject was not evaluable for response and was replaced after withdrawing from the study before response evaluation. |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 6 | 6 | 6 | 16 |
| Count of Participants [Participants] |
2
33.3%
|
3
42.9%
|
4
66.7%
|
7
43.8%
|
| Title | Clinical Benefit Rate |
|---|---|
| Description | 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). |
| Time Frame | At 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects with a Partial Response (PR) or Stable Disease (SD) treated at the RP2D. No subjects achieved a Complete Response (CR) while on study. |
| Arm/Group Title | Treatment (Avelumab, Trabectedin) |
|---|---|
| Arm/Group Description | Subjects enrolled in Phase 2 plus subjects treated at the Recommended Phase 2 dose. |
| Measure Participants | 23 |
| Number [percentage of participants] |
56
933.3%
|
| Title | Median Overall Survival (OS) |
|---|---|
| Description | Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Time Frame | Up to 2 years post End of Treatment, for a total of 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 6 | 7 | 6 | 16 |
| Number (95% Confidence Interval) [days] |
391
|
416
|
NA
|
NA
|
| Title | Adverse Event Profile - All Treatment-Related Grade 3-5 Adverse Events |
|---|---|
| Description | Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
| Time Frame | Up to 2 years 7 months total |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2 mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin |
|---|---|---|---|---|
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV | 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. Avelumab: Given IV Trabectedin: Given IV |
| Measure Participants | 6 | 7 | 6 | 16 |
| Alanine Aminotransferase Increased |
1
|
1
|
1
|
3
|
| Lymphocyte Count Decreased |
0
|
0
|
0
|
4
|
| Neutrophil Count Decreased |
1
|
2
|
0
|
0
|
| Anemia |
0
|
0
|
0
|
2
|
| Ejection Fraction Decreased |
1
|
0
|
1
|
0
|
| Aspartate Aminotransferase Increased |
0
|
0
|
0
|
1
|
| Blood Bilirubin Increased |
1
|
0
|
0
|
0
|
| Dyspnea |
0
|
0
|
0
|
1
|
| Fatigue |
0
|
0
|
0
|
1
|
| Gastrointestinal Disorders - Other |
0
|
1
|
0
|
0
|
| GGT Increased |
1
|
0
|
0
|
0
|
| Hepatobiliary Disorders - Other |
1
|
0
|
0
|
0
|
| Hypophosphatemia |
1
|
0
|
0
|
0
|
| Infections and Infestations - Other (Port Infection/Inflammation/Erythema) |
1
|
0
|
0
|
0
|
| Infusion Related Reaction |
0
|
0
|
0
|
1
|
| Muscle Weakness Lower Limb |
0
|
0
|
0
|
1
|
| Respiratory Failure |
1
|
0
|
0
|
0
|
| Syncope |
1
|
0
|
0
|
0
|
| White Blood Cell Decreased |
1
|
0
|
0
|
0
|
Adverse Events
| Time Frame | Adverse events (AE) will be monitored from the time of first exposure to study drug (Cycle 1 Day 1) through 90 days following the last dose of a study drug, up to 2 years 7 months total. All-cause mortality was assessed from enrollment to end of study or subject death, up to 3 years total. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin | ||||
| Arm/Group Description | 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. Avelumab: Given IV Trabectedin: Given IV | 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. | 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. | 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. Avelumab: Given IV Trabectedin: Given IV | ||||
All Cause Mortality |
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| Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/6 (66.7%) | 5/7 (71.4%) | 2/6 (33.3%) | 1/16 (6.3%) | ||||
Serious Adverse Events |
||||||||
| Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | 2/7 (28.6%) | 1/6 (16.7%) | 7/16 (43.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Cardiac disorders | ||||||||
| Tricuspid valve disease | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Gastrointestinal disorders | ||||||||
| Gastrointestinal disorders - other | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Gastrointestinal disorders - other | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Abdominal Pain | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Rectal hemorrhage | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Upper gastrointestinal hemorrhage | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Gastrointestinal disorders - other | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Gastrointestinal disorders - other | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| General disorders | ||||||||
| Fever | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hepatobiliary disorders | ||||||||
| LFT Elevation | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Infections and infestations | ||||||||
| Enterocolitis infectious | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Urinary tract infection | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Biliary tract infection | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tricuspid valve mass | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Tumor Pain | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Nervous system disorders | ||||||||
| Seizure | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Syncope | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Respiratory failure | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Hypoxia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pleural effusion | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pneumothorax | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Vascular disorders | ||||||||
| Hypotension | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pulmonary Embolism | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
Other (Not Including Serious) Adverse Events |
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| Phase 1 - 1.5 mg/m^2 Trabectedin | Phase 1 - 1.0 mg/m^2 Trabectedin | Phase 1 - 1.2mg/m^2 Trabectedin | Phase 2 - 1.0 mg/m^2 Trabectedin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 7/7 (100%) | 6/6 (100%) | 16/16 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 0/6 (0%) | 0 | 1/7 (14.3%) | 2 | 1/6 (16.7%) | 1 | 6/16 (37.5%) | 11 |
| Leukocytosis | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Cardiac disorders | ||||||||
| Palpitations | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 3/16 (18.8%) | 3 |
| Sinus tachycardia | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Chest Pain - Cardiac | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Ventricular arrhythmia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Tricuspid Valve Disease | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Cardiac Disorders - Other | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Endocrine disorders | ||||||||
| Hypothyroidism | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/16 (18.8%) | 4 |
| Hyperparathyroidism | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Endocrine Disorders - Other | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Eye disorders | ||||||||
| Blurred Vision | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 2/16 (12.5%) | 2 |
| Dry eye | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Floaters | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Watering Eyes | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Eye Disorders - Other | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Nausea | 6/6 (100%) | 8 | 5/7 (71.4%) | 5 | 3/6 (50%) | 3 | 13/16 (81.3%) | 14 |
| Diarrhea | 5/6 (83.3%) | 5 | 4/7 (57.1%) | 10 | 4/6 (66.7%) | 6 | 6/16 (37.5%) | 7 |
| Vomiting | 5/6 (83.3%) | 7 | 2/7 (28.6%) | 4 | 3/6 (50%) | 4 | 8/16 (50%) | 9 |
| Constipation | 1/6 (16.7%) | 1 | 3/7 (42.9%) | 3 | 4/6 (66.7%) | 6 | 5/16 (31.3%) | 5 |
| Abdominal Pain | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 2/6 (33.3%) | 3 | 3/16 (18.8%) | 4 |
| Gastroesophageal reflux disease | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Dry Mouth | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Oral pain | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Flatulence | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Stomach Pain | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 0/16 (0%) | 0 |
| Mucositis oral | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Rectal hemorrhage | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Active Diverticulitis | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Dyspepsia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Gastrointestinal disorders - other | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Ascites | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Toothache | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Colitis | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Colonic obstruction | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 6/6 (100%) | 8 | 6/7 (85.7%) | 6 | 5/6 (83.3%) | 6 | 16/16 (100%) | 19 |
| Pain | 4/6 (66.7%) | 6 | 2/7 (28.6%) | 4 | 0/6 (0%) | 0 | 4/16 (25%) | 4 |
| Flu like symptoms | 1/6 (16.7%) | 1 | 3/7 (42.9%) | 6 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Fever | 2/6 (33.3%) | 3 | 2/7 (28.6%) | 3 | 0/6 (0%) | 0 | 3/16 (18.8%) | 8 |
| Chills | 1/6 (16.7%) | 2 | 2/7 (28.6%) | 3 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Non-cardiac chest pain | 1/6 (16.7%) | 2 | 2/7 (28.6%) | 3 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Edema limbs | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 1 | 2/16 (12.5%) | 3 |
| Soreness | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Localized edema | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Pyrosis | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Body Aches | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Immune system disorders | ||||||||
| Urinary Tract Infection | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Infections and infestations | ||||||||
| Upper Respiratory Infection | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Dry Skin | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 3/16 (18.8%) | 3 |
| Infections and infestations - Other | 3/6 (50%) | 3 | 3/7 (42.9%) | 3 | 3/6 (50%) | 3 | 4/16 (25%) | 5 |
| Sinusitis | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Skin Infection | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Enterocolitis infectious | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Lip Infection | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Biliary tract infection | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Infective myositis | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Enterocolitis infectious | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Urinary tract infection | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Infusion related reaction | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 2 | 2/6 (33.3%) | 2 | 8/16 (50%) | 12 |
| Bruising | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/16 (18.8%) | 3 |
| Wound complication | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Fracture | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Investigations | ||||||||
| Alanine aminotransferase increase | 3/6 (50%) | 5 | 1/7 (14.3%) | 2 | 5/6 (83.3%) | 7 | 6/16 (37.5%) | 19 |
| Aspartate aminotransferase increased | 3/6 (50%) | 4 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 5/16 (31.3%) | 9 |
| Lymphocyte count decreased | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 11/16 (68.8%) | 20 |
| Creatinine Increaed | 2/6 (33.3%) | 3 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/16 (18.8%) | 5 |
| Alkaline Phosphatase Increased | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/16 (12.5%) | 9 |
| Weight loss | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 3/16 (18.8%) | 4 |
| Neutrophil count decreased | 1/6 (16.7%) | 1 | 3/7 (42.9%) | 9 | 0/6 (0%) | 0 | 1/16 (6.3%) | 2 |
| Platelet count decreased | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 | 1/6 (16.7%) | 6 | 2/16 (12.5%) | 4 |
| White blood cell decreased | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/16 (12.5%) | 4 |
| Ejection fraction decreased | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 0/16 (0%) | 0 |
| CPK increased | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Cardiac troponin I increased | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| INR Increased | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Blood bilirubin increased | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| GGT increased | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Investigations - Other | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hypophosphatemia | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Hypoglycemia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Hyponatremia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 3/6 (50%) | 3 | 4/7 (57.1%) | 4 | 5/6 (83.3%) | 6 | 8/16 (50%) | 8 |
| Hypokalemia | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Hypocalcemia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 4/16 (25%) | 4 |
| Dehydration | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Hypoalbuminemia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Bone Pain | 2/6 (33.3%) | 2 | 3/7 (42.9%) | 3 | 2/6 (33.3%) | 2 | 6/16 (37.5%) | 6 |
| Myalgia | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 | 3/6 (50%) | 5 | 5/16 (31.3%) | 5 |
| Generalized muscle weakness | 3/6 (50%) | 3 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/16 (12.5%) | 3 |
| Pain in extremity | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 2/16 (12.5%) | 3 |
| Arthralgia | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Neck Pain | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Back Pain | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Muscle Cramp | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Musculoskeletal and connective tissue disorders - other | 2/6 (33.3%) | 2 | 4/7 (57.1%) | 4 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Chest Wall Pain | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Tumor Pain | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 1/6 (16.7%) | 2 | 1/16 (6.3%) | 3 |
| Sebaceous Cyst | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Nervous system disorders | ||||||||
| Headache | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 3 | 3/6 (50%) | 3 | 4/16 (25%) | 7 |
| Dysgeusia | 3/6 (50%) | 3 | 2/7 (28.6%) | 2 | 2/6 (33.3%) | 2 | 4/16 (25%) | 4 |
| Dizziness | 3/6 (50%) | 3 | 1/7 (14.3%) | 2 | 2/6 (33.3%) | 3 | 2/16 (12.5%) | 2 |
| Nervous System Disorders - Other | 2/6 (33.3%) | 3 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Tremor | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/16 (18.8%) | 3 |
| Paresthesia | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Syncope | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Extrapyramidal disorder | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Cognitive disturbance | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Presyncope | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Radiculitis | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Lethargy | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Peripheral sensory neuropathy | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hallucinations | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Confusion | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Concentration impairment | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Neuralgia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Insomnia | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 2 | 2/6 (33.3%) | 2 | 2/16 (12.5%) | 2 |
| Anxiety | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Depression | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 1/16 (6.3%) | 1 |
| Psychiatric disorders - Other | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Urinary frequency | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Renal and urinary disorders - Other | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Urinary tract obstruction | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Acute Kidney Injury | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Hematuria | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Irregular menstruation | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Pelvic Pain | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnea | 4/6 (66.7%) | 4 | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 5/16 (31.3%) | 10 |
| Cough | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 4 | 4/16 (25%) | 4 |
| Postnasal drip | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Hoarseness | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Sore throat | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Rhinorrhea | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Wheezing | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Allergic rhinitis | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/16 (12.5%) | 2 |
| Hypoxia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pleural effusion | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Bronchospasm | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pulmonary edema | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Nasal congestion | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pneumothorax | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Respiratory failure | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Epistaxis | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 3 | 4/16 (25%) | 5 |
| Hyperhidrosis | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 2 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Rash acneiform | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/16 (18.8%) | 3 |
| Skin and subcutaneous tissue disorders - Other | 3/6 (50%) | 3 | 3/7 (42.9%) | 3 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Pain of skin | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Rash maculo-papular | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 1/16 (6.3%) | 3 |
| Skin Hyperpigmentation | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Alopecia | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Skin Hypopigmentation | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Erythema multiforme | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Photosensitivity | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Burn | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
| Scalp Pain | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/16 (0%) | 0 |
| Surgical and medical procedures | ||||||||
| Surgical and Medical Procedures - Other | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 1/16 (6.3%) | 1 |
| Vascular disorders | ||||||||
| Hot flashes | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 3/16 (18.8%) | 3 |
| Hypotension | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Thromboembolic event | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 1/16 (6.3%) | 1 |
| Hematoma | 0/6 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/16 (6.3%) | 1 |
| Vascular disorders - other | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/16 (6.3%) | 2 |
| Flushing | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/16 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Seth Pollack, MD, Director of Sarcoma Program |
|---|---|
| Organization | Northwestern University |
| Phone | 312-503-5320 |
| seth.pollack@northwestern.edu |
Responsible Party:
Seth Pollack,
Associate Professor of Medicine (Hematology and Oncology),
Northwestern University
ClinicalTrials.gov Identifier:
NCT03074318
Other Study ID Numbers:
- 9717
- NCI-2017-00234
- 9717
- P30CA015704
- RG9217009
First Posted:
Mar 8, 2017
Last Update Posted:
Apr 29, 2022
Last Verified:
Apr 1, 2022