Paclitaxel-Avelumab for Angiosarcoma (ASAP)

Phase II Trial, Multicenter, First Line Paclitaxel-Avelumab Treatment for Inoperable Angiosarcoma

To investigate the efficacy of Avelumab when given in combination with paclitaxel as a first line treatment for the patients with inoperable angiosarcoma.

Study Overview

• Status: Recruiting
• Conditions: Angiosarcoma Metastatic
• Intervention / Treatment: Drug: Avelumab; Drug: Paclitaxel

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.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: SUNG YONG OH, MD; Phone Number: +82-51-240-2808; Email: drosy@dau.ac.kr

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Recruiting
    • Sung Yong Oh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paclitaxel+Avelumab; Paclitaxel combination with Avelumab for inoperable angiosarcoma	Drug: Avelumab; Avelumab 10mg/kg, administered via I.V infusion over 1hour, every 2weeks until disease progression or unacceptable toxicity; Other Names: BAVENCIO; Drug: Paclitaxel; Paclitaxel 80mg/m2 D1,8 and 15 , administered via I.V infusion, every 4 weeks.; Other Names: TAXOL; GENEXOL; ANZATAX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	CR+PR by RECIST	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	progression or death	up to 12 months
Overall survival	death event	up to 12 months
Adverse event	By NCI-CTC v4.03	up to 12 months

Collaborators and Investigators

• Sponsor: Sung Yong Oh
• Collaborators: Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: April 19, 2018
• First Posted (Actual): May 1, 2018

Study Record Updates

• Last Update Posted (Actual): July 11, 2018
• Last Update Submitted That Met QC Criteria: July 10, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: paclitaxel; angiosarcoma; avelumab
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Vascular Tissue; Hemangiosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Avelumab
• Other Study ID Numbers: DAUHIRB-18-052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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