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Paclitaxel-Avelumab for Angiosarcoma (ASAP)

Primary Purpose

Angiosarcoma Metastatic

Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Avelumab
Paclitaxel
Sponsored by
Sung Yong Oh
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Angiosarcoma Metastatic focused on measuring angiosarcoma, paclitaxel, avelumab

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed written informed consent.
  2. Male or female subjects aged ≥ 20 years.
  3. Histologically or cytologically proven metastatic or locally advanced Angiosarcoma.
  4. Inoperable Angiosarcoma
  5. Chemo-naïve patient
  6. ECOG performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months.
  7. Disease must be measurable with at least 1 measurable lesion by RECIST 1.1
  8. Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
  9. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels

    ≤ 5 × ULN.

  10. Adequate renal function defined by an estimated creatinine clearance > 30mL/min according to the Cockcroft-Gault formula.
  11. Highly effective contraception (that is, methods with a failure rate of less than 1% per year) for both male and female subjects if the risk of conception exists

Exclusion Criteria:

  1. Concurrent treatment with a non-permitted drug (see Section 14)
  2. Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody.
  3. Concurrent anticancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin)
  4. Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy)
  5. Use of hormonal agents within 7 days before the start of trial treatment.
  6. Use of any investigational drug within 28 days before the start of trial treatment.
  7. Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of patients with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
  8. Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ.
  9. Rapidly progressive disease (e.g., tumor lysis syndrome).
  10. Active or history of central nervous system (CNS) metastases.
  11. Receipt of any organ transplantation including allogeneic stem-cell transplantation.
  12. Significant acute or chronic infections including, among others:

    1. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    2. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive).
  13. Active or history of any autoimmune disease (subjects with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
  14. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partly controlled asthma).
  15. Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v4.0, however sensory neuropathy

    ≤ Grade 2 is acceptable.

  16. Pregnancy or breast feeding.
  17. Known alcohol or drug abuse.
  18. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
  19. All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment.
  20. Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  21. Legal incapacity or limited legal capacity.
  22. Vaccination within 4 weeks of the first dose of avelumab and while on study is prohibited except for administration of inactivated vaccines (e.g. inactivated influenza vaccines).

Sites / Locations

  • Sung Yong OhRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Paclitaxel+Avelumab

Arm Description

Paclitaxel combination with Avelumab for inoperable angiosarcoma

Outcomes

Primary Outcome Measures

Overall response rate
CR+PR by RECIST

Secondary Outcome Measures

Progression free survival
progression or death
Overall survival
death event
Adverse event
By NCI-CTC v4.03

Full Information

First Posted
April 19, 2018
Last Updated
July 10, 2018
Sponsor
Sung Yong Oh
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT03512834
Brief Title
Paclitaxel-Avelumab for Angiosarcoma
Acronym
ASAP
Official Title
Phase II Trial, Multicenter, First Line Paclitaxel-Avelumab Treatment for Inoperable Angiosarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Unknown status
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sung Yong Oh
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To investigate the efficacy of Avelumab when given in combination with paclitaxel as a first line treatment for the patients with inoperable angiosarcoma.
Detailed Description
Angiosarcomas are very rare tumors (incidence < 1/100.000/year) of vascular or lymphatic origin characterized by a clinical heterogeneity in terms of presentation and behavior.In several prospective and retrospective studies, weekly paclitaxel showed promising activity in patients with advanced or metastatic angiosarcoma. Given the important role of PD-L1 in the suppression of T-cell responses, and the mode of action of avelumab which blocks the interaction between PD-L1 and its receptors, avelumab is being developed as a potential therapy for subjects with various tumors. In prior study cutaneous angiosarcoma patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival. Therefore, antitumor activity of Avelumab as inhibitor of PD-1/PDL-1 interaction with Paclitaxel, standard chemotherapy, might have more therapeutic improvement.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angiosarcoma Metastatic
Keywords
angiosarcoma, paclitaxel, avelumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Paclitaxel + Avelumab
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Paclitaxel+Avelumab
Arm Type
Experimental
Arm Description
Paclitaxel combination with Avelumab for inoperable angiosarcoma
Intervention Type
Drug
Intervention Name(s)
Avelumab
Other Intervention Name(s)
BAVENCIO
Intervention Description
Avelumab 10mg/kg, administered via I.V infusion over 1hour, every 2weeks until disease progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
TAXOL, GENEXOL, ANZATAX
Intervention Description
Paclitaxel 80mg/m2 D1,8 and 15 , administered via I.V infusion, every 4 weeks.
Primary Outcome Measure Information:
Title
Overall response rate
Description
CR+PR by RECIST
Time Frame
up to 6 months
Secondary Outcome Measure Information:
Title
Progression free survival
Description
progression or death
Time Frame
up to 12 months
Title
Overall survival
Description
death event
Time Frame
up to 12 months
Title
Adverse event
Description
By NCI-CTC v4.03
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed written informed consent. Male or female subjects aged ≥ 20 years. Histologically or cytologically proven metastatic or locally advanced Angiosarcoma. Inoperable Angiosarcoma Chemo-naïve patient ECOG performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months. Disease must be measurable with at least 1 measurable lesion by RECIST 1.1 Adequate hematological function defined by white blood cell (WBC) count ≥ 3 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused). Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN. Adequate renal function defined by an estimated creatinine clearance > 30mL/min according to the Cockcroft-Gault formula. Highly effective contraception (that is, methods with a failure rate of less than 1% per year) for both male and female subjects if the risk of conception exists Exclusion Criteria: Concurrent treatment with a non-permitted drug (see Section 14) Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody. Concurrent anticancer treatment within 28 days before the start of trial treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin) Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy) Use of hormonal agents within 7 days before the start of trial treatment. Use of any investigational drug within 28 days before the start of trial treatment. Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of patients with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily). Steroids with no or minimal systemic effect (topical, inhalation) are allowed. Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ. Rapidly progressive disease (e.g., tumor lysis syndrome). Active or history of central nervous system (CNS) metastases. Receipt of any organ transplantation including allogeneic stem-cell transplantation. Significant acute or chronic infections including, among others: Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive). Active or history of any autoimmune disease (subjects with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partly controlled asthma). Persisting toxicity related to prior therapy Grade > 1 NCI-CTCAE v4.0, however sensory neuropathy ≤ Grade 2 is acceptable. Pregnancy or breast feeding. Known alcohol or drug abuse. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication. All other significant diseases (e.g., inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment. Any psychiatric condition that would prohibit the understanding or rendering of informed consent. Legal incapacity or limited legal capacity. Vaccination within 4 weeks of the first dose of avelumab and while on study is prohibited except for administration of inactivated vaccines (e.g. inactivated influenza vaccines).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
SUNG YONG OH, MD
Phone
+82-51-240-2808
Email
drosy@dau.ac.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
SUNG YONG OH, MD
Organizational Affiliation
Dong-A University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sung Yong Oh
City
Busan
ZIP/Postal Code
602-715
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SUNG YONG OH, Professor
Email
drosy@dau.ac.kr

12. IPD Sharing Statement

Plan to Share IPD
No

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Paclitaxel-Avelumab for Angiosarcoma

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