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A Study of an Intratumoral Oncolytic Virus in Patients With Advanced Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT03954067
Recruitment Status : Recruiting
First Posted : May 17, 2019
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:
The purpose of this study is to assess the safety and tolerability of ASP9801 and to determine the recommended phase 2 dose (RP2D). The study will also evaluate antitumor activity, objective response rate, pharmacokinetics and virus shedding of ASP9801.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Solid Tumors Advanced Cancer Biological: ASP9801 Phase 1

Detailed Description:
The study consists of two parts: dose escalation and recommended phase 2 dose expansion. Each part of the study will include two separate groups of participants. Group A will include participants who will have cutaneous/subcutaneous tumors injected, and group B will include participants who will have visceral tumors injected. The study will consist of the following periods: screening, initial treatment period (two 28 day cycles), optional extended treatment period (continued 28 day cycles) and a follow up period (safety and survival follow up).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label Study of ASP9801, an Oncolytic Virus, Administered by Intratumoral Injection in Patients With Advanced/Metastatic Solid Tumors
Actual Study Start Date : August 8, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: Dose Escalation - cutaneous or subcutaneous lesions
Participants will receive ASP9801 on days 1 and 15 of 28 day cycles to determine the recommended phase 2 dose. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
Biological: ASP9801
Administered by intratumoral injection

Experimental: Dose Escalation - visceral lesions
Participants will receive ASP9801 on days 1 and 15 of 28 day cycles to determine the recommended phase 2 dose. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
Biological: ASP9801
Administered by intratumoral injection

Experimental: Dose Expansion - cutaneous or subcutaneous lesions
Participants will receive ASP9801 on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
Biological: ASP9801
Administered by intratumoral injection

Experimental: Dose Expansion - visceral lesions
Participants will receive ASP9801 on days 1 and 15 of 28 day cycles at the dose recommended by the dose escalation phase. After cycle 2, participants who have not met any discontinuation criteria and receiving clinical benefit may be treated on continuous cycles until treatment discontinuation criteria are met.
Biological: ASP9801
Administered by intratumoral injection




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLT) - dose escalation part [ Time Frame: Up to 28 days ]
    Incidence of dose limiting toxicities

  2. Safety and tolerability assessed by Adverse Events (AEs) [ Time Frame: Up to 12 months ]
    An AE is any untoward medical occurrence in a subject administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP.

  3. Number of participants with laboratory value abnormalities and/or adverse events [ Time Frame: Up to 12 months ]
    Number of participants with potentially clinically significant laboratory values.

  4. Number of participants with vital sign abnormalities and /or adverse events [ Time Frame: Up to 12 months ]
    Number of participants with potentially clinically significant vital sign values.

  5. Safety assessed by 12- lead electrocardiograms (ECGs) adverse events [ Time Frame: Up to 12 months ]
    12-lead ECGs will be read and assessed locally. Any clinically significant adverse changes on the ECG will be reported as Adverse Events.


Secondary Outcome Measures :
  1. Percent change from baseline in antitumor activity of ASP9801 [ Time Frame: Up to 12 months ]
    Percent change from baseline in sum of diameters of injected tumors per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and immune modified response evaluation criteria in solid tumors (imRECIST)

  2. Objective Response Rate [ Time Frame: Up to 12 months ]
    Partial Response (PR) + Complete Response (CR) per imRECIST

  3. ASP9801 viral DNA in blood [ Time Frame: Up to 12 months ]
    Viral DNA load will be summarized by cohort using descriptive statistics.

  4. Viral shedding of ASP9801 in saliva [ Time Frame: Up to 12 months ]
    Viral DNA will be analyzed by quantitative polymerase chain reaction (qPCR).

  5. Viral shedding of ASP9801 in urine [ Time Frame: Up to 12 months ]
    Viral DNA will be analyzed by qPCR.

  6. Viral shedding of ASP9801 in skin (cutaneous/subcutaneous only) [ Time Frame: Up to 12 months ]
    Viral DNA will be analyzed by qPCR.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Subject must have histologically- or cytologically-confirmed diagnosis of advanced or metastatic solid tumor(s).
  • Subject has measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. At least 1 lesion must be suitable for intratumoral (IT) injection. Lesions for injection must be ≥ 10 mm and ≤ 60 mm in longest diameter.
  • Subject has progressed on or is not eligible for available standard therapy.
  • Subject has a predicted life expectancy ≥ 12 weeks.
  • Subject has at least 2 sites of disease suitable for biopsy and is willing and able to undergo required tumor biopsies according to the treating institution's guidelines at screening and during study treatment.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • A female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:

    • Not a woman of childbearing potential (WOCBP) OR
    • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study investigational product (IP) administration.
  • Female subject must agree not to breastfeed starting at screening, and throughout the study period and 180 days after the final study IP administration.
  • Female subject must not donate ova starting at screening, and throughout the study period and for 180 days after the final study IP administration.
  • Male subject must agree to remain abstinent or use a condom throughout the study period and for 180 days after the final study IP administration.
  • Male subject with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 180 days after the final study IP administration.
  • Male subject must not donate sperm during the treatment period and for at least 180 days after the final study IP administration.
  • Subject must be willing and able to comply with the study requirements including prohibited concomitant medication restrictions.
  • Subject agrees not to participate in another interventional study while receiving study IP.
  • Subject has the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Subject has ongoing toxicity ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2 attributable to prior antineoplastic therapies considered clinically significant.
  • Subject who has had major surgery ≤ 4 weeks of screening.
  • Subject is concurrently participating in another interventional study or has received an investigational product ≤ 30 days or 5 half-lives prior to first IP administration.
  • Subject with symptomatic or untreated central nervous system metastases or leptomeningeal disease. Subjects with treated symptomatic brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to screening) and off steroids for at least 2 weeks prior to first IP administration.
  • Subject with active or prior autoimmune or inflammatory disorders requiring systemic therapy within past 2 years (including inflammatory skin conditions or severe eczema, inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis), celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.

The following are exceptions to this criterion:

  • Subject with vitiligo or alopecia
  • Subject with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy

    • Subject with another malignancy that currently requires treatment.
    • Subject with tumors encasing major vascular structures such as the carotid artery, tumors adjacent to vital neurovascular structures or tumors in locations that are at high risk for adverse events (AEs) or otherwise not considered appropriate for IT injection.
    • Subject with inadequate organ and marrow functions meeting any of the below criteria:
  • Leukocytes < 3000/μL
  • Absolute neutrophil count < 1500/μL
  • Platelets < 100,000/μL
  • Hemoglobin (Hgb) < 9 g/dL
  • International normalized ratio (INR) > 1.5 × ULN and/or activated partial thromboplastin time (aPTT) > 1.5 × institutional normal limits, except for patients in Group B (Visceral Lesions) escalation and expansion groups where INR and aPTT must be normal
  • Total Bilirubin (TBL) > 1.5 × institutional normal limits (subjects with known Gilbert syndrome who are excluded if TBL > 3.0 × institutional normal limits or direct bilirubin > 1.5 × institutional normal limits)
  • Aspartate aminotransferase (AST) and Alanine transaminase (ALT) > 3.0 × institutional normal limits. Subjects with tumors in the liver AST and ALT > 5 × institutional normal limits.
  • Albumin < 3.4 g/dL
  • Creatinine > 1.5 × institutional normal limits

    • Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of first administration of study IP. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
    • Subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, any form of substance abuse or psychiatric illness/social situations that would limit compliance with study visits or requirements or a condition that could invalidate communication with the investigator.
    • Subject is known to be positive for human immunodeficiency virus, hepatitis B surface antigen, hepatitis B core immunoglobulin or immunoglobulin G (IgG) antibody or hepatitis C (IgG or ribonucleic acid (RNA) test) indicating acute or chronic infection.
    • Subject has a history of moderate to severe ascites, clinically significant and/or rapidly accumulating ascites, bleeding esophageal varices, hepatic encephalopathy or pericardial and/or pleural effusions related to liver insufficiency within 6 months of screening. Mild ascites that does not preclude safe IT injection of ASP9801 is allowed.
    • Subject has a clinically significant abnormal electrocardiogram (ECG) at screening.
    • Subject has symptomatic cardiovascular disease within the preceding 12 months unless cardiology consultation and clearance has been obtained for study participation, including but not limited to the following: significant coronary artery disease (e.g., requiring angioplasty or stenting), acute myocardial infarction or unstable angina pectoris < 3 months prior to screening, uncontrolled hypertension, clinically significant arrhythmia or congestive heart failure (New York Heart Association grade ≥ 2).
    • Subject has medical conditions that predispose the subject to untoward medical risk in the event of volume loading (e.g., intravenous fluid bolus infusion), tachycardia or hypotension during or following treatment with ASP9801.
    • Subject has a known or suspected hypersensitivity to ASP9801 or any components of the formulation used, including prior adverse reaction to vaccinia (e.g., as smallpox vaccine).
    • Subject has had previous exposure with ASP9801.

Information from the National Library of Medicine

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

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03954067


Contacts
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Contact: Astellas Pharma Global Development 800-888-7704 astellas.registration@astellas.com

Locations
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United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68130
United States, Ohio
University of Toledo Medical Center Recruiting
Toledo, Ohio, United States, 43614
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75251
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
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Study Director: Medical Director Astellas Pharma Global Development, Inc.

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Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03954067     History of Changes
Other Study ID Numbers: 9801-CL-0101
First Posted: May 17, 2019    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
immunotherapy
vaccinia virus
visceral lesions
cutaneous lesions
intratumoral injection
ASP9801
subcutaneous lesions
oncolytic virus
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes