Clinical Trials /

Study of T-VEC in Locally Advanced Cutaneous Angiosarcoma

NCT03921073

Description:

This is a single-arm study evaluating the efficacy of injecting Talimogene Laherparepvec T-VEC into Cutaneous Angiosarcoma tumors.

Related Conditions:
  • Angiosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of T-VEC in Locally Advanced Cutaneous Angiosarcoma
  • Official Title: A Phase II Study of Talimogene Laherparepvec (T-VEC) in the Treatment of Locally Advanced Cutaneous Angiosarcoma

Clinical Trial IDs

  • ORG STUDY ID: MCC-19878
  • NCT ID: NCT03921073

Conditions

  • Angiosarcoma of Skin

Interventions

DrugSynonymsArms
T-VECIntralesional injection of T-VEC

Purpose

This is a single-arm study evaluating the efficacy of injecting Talimogene Laherparepvec T-VEC into Cutaneous Angiosarcoma tumors.

Trial Arms

NameTypeDescriptionInterventions
Intralesional injection of T-VECExperimentalParticipants will undergo intralesional injections of up to 4 cc of 10^6 plaque-forming units (PFU)/mL of T-VEC. Dose is dependent on the diameter of the lesions to be injected (volume injected is related to diameter of lesion(s) at time point 0). Three weeks later and every other week thereafter, the participants will be injected with up to 4 cc of 10^8 PFU/mL, with dose dependent on the diameter of the lesion(s) to be injected. Participants may be treated for up to 12 months.
  • T-VEC

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed CA without visceral or CNS metastases,
             with resection deemed of no benefit by technical or oncologic principles, and have
             progressed on at least one line of systemic therapy

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded by
             digital photography) as >6 mm with calipers or a ruler.

          -  Eastern Cooperative Oncology Group performance status 0-1 (Karnofsky >70%).

          -  Participants must have normal organ and marrow function as defined below:

          -  Hematological

          -  Absolute neutrophil count > 1500/mm3 (1.5x109/L)

          -  Platelet count >75,000/mm3 (7.5x109/L)

          -  Hemoglobin >8 g/dL (without need for hematopoietic growth factor or transfusion
             support)

          -  Renal

          -  Serum creatinine ≤1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance
             >60 mL/min for subject with creatinine levels > 1.5 x ULN. (Note: Creatinine clearance
             need not be determined if the baseline serum creatinine is ≤1.5 x ULN. . Creatinine
             clearance should be determined per institutional standard).

          -  Hepatic

          -  Serum bilirubin ≤1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total
             bilirubin level > 1.5 x ULN

          -  Aspartate aminotransferase (AST) ≤2.5 x ULN OR <5 x ULN, if liver metastases present
             and injection does not involve a visceral lesion

          -  Alanine aminotransferase (ALT) ≤2.5 x ULN OR <5 x ULN, if liver metastases present and
             injection does not involve a visceral lesion

          -  Coagulation

          -  International normalization ratio (INR) or prothrombin time (PT) ≤1.5 x ULN, unless
             the subject is receiving anticoagulant therapy, in which case PT and partial
             thromboplastin time (PTT)/ activated PTT (aPTT) must be within therapeutic range of
             intended use of anticoagulants.

          -  PTT or aPTT ≤1.5 x ULN, unless the subject is receiving anticoagulant therapy as long
             as PT and PTT/aPTT is within therapeutic range of intended use of anticoagulants.-
             Female subjects of childbearing potential should have a negative urine or serum
             pregnancy test within 72 hours prior to enrollment. If urine test is positive or
             cannot be confirmed as negative, a serum pregnancy test will be required.

        Exclusion Criteria:

          -  Participants with a second active malignancy, exceptions are localized non-melanoma
             skin cancers or in situ carcinoma

          -  Participants receiving any other investigational agents

          -  Participants with tumor(s) in direct contact or encasing a major blood vessel, those
             with ulceration and/or fungation onto the skin surface, and those with history of
             re-irradiation or prior lymph node neck dissection to a field involving the carotid
             arteries

          -  History or evidence of active autoimmune disease that requires systemic treatment (ie,
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
             Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
             therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
             systemic treatment.

          -  Evidence of clinically significant immunosuppression such as the following:

          -  Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease.

          -  concurrent opportunistic infection.

          -  receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses
             > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment.

          -  Active herpetic skin lesions or prior complications of HSV-1 infection (e.g., herpetic
             keratitis or encephalitis).

          -  Requires intermittent or chronic systemic (intravenous or oral) treatment with an
             antiherpetic drug (e.g., acyclovir), other than intermittent topical use.

          -  Previous treatment with talimogene laherparepvec or any other oncolytic virus.

          -  Prior therapy with tumor vaccine.

          -  Received live vaccine within 28 days prior to enrollment.

          -  Prior immunosuppressive, chemotherapy, radiotherapy (in which the field encompassed a
             planned injection site), biological cancer therapy, or major surgery within 28 days
             prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event
             due to cancer therapy administered more than 28 days prior to enrollment.

          -  Prior radiotherapy in which the field does not overlap the injection sites or
             non-immunosuppressive targeted therapy within 14 days prior to enrollment or has not
             recovered to CTCAE grade 1 or better from adverse event due to cancer therapy
             administered more than 14 days prior to enrollment

          -  Currently receiving treatment with another investigational device or drug study, or <
             28 days since ending treatment with another investigational device or drug study(s).

          -  Other investigational procedures while participating in this study are excluded.

          -  Known to have acute or chronic active hepatitis B infection, hepatitis C infection, or
             human immunodeficiency virus (HIV) infection.

          -  History of other malignancy within the past 5 years with the following exceptions:
             adequately treated non melanoma skin cancer, cervical carcinoma in situ, breast ductal
             carcinoma in situ, or prostatic intraepithelial neoplasia without evidence of disease
             at the time of enrollment

          -  Participant has known sensitivity to talimogene laherparepvec or any of its components
             to be administered during dosing.

          -  Female subject is pregnant or breast-feeding, or planning to become pregnant during
             study treatment and through 3 months after the last dose of talimogene laherparepvec.

          -  Female subject of childbearing potential who is unwilling to use acceptable method(s)
             of effective contraception during study treatment and through 3 months after the last
             dose of talimogene laherparepvec.

          -  Sexually active subjects and their partners unwilling to use male or female latex
             condom to avoid potential viral transmission during sexual contact while on treatment
             and within 30 days after treatment with talimogene laherparepvec.

          -  Participants who are unwilling to minimize exposure with his/her blood or other body
             fluids to individuals who are at higher risks for HSV-1 induced complications such as
             immunosuppressed individuals, individuals known to have HIV infection, pregnant women,
             or infants under the age of 3 months, during talimogene laherparepvec treatment and
             through 30 days after the last dose of talimogene laherparepvec.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:at 24 Weeks
Safety Issue:
Description:Overall response rate is defined as the proportion of patients who demonstrate complete or partial responses in injected lesions per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria appropriate for cutaneous neoplasms (ORR=complete response + partial response).

Secondary Outcome Measures

Measure:Duration of response
Time Frame:at 4 weeks
Safety Issue:
Description:Response duration will be measured from the time of initial partial response or complete response until documented progression. The duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measure:Progression-free Survival
Time Frame:up to 2 years
Safety Issue:
Description:Progression-free survival is defined as the period of time from the first injection to progression of disease or appearance of new cutaneous angiosarcomas that were not present at the time of study entry
Measure:Complete Response Rate
Time Frame:Baseline to 2 years
Safety Issue:
Description:Complete response rate is defined as the proportion of participants that have lesions with complete clinical regression
Measure:Adverse Events after T-VEC injections
Time Frame:Baseline to 2 years
Safety Issue:
Description:Monitoring Adverse Events after participants receive injections of T-VEC into Cutaneous Angiosarcoma
Measure:T-VEC treated tumors requiring surgical resection
Time Frame:Baseline to 2 years
Safety Issue:
Description:Measuring the rate of participants requiring surgical resection of T-VEC treated lesions
Measure:Analyses of immune infiltration within resected tumor specimens
Time Frame:Baseline to 2 years
Safety Issue:
Description:Measuring the degree of immune infiltration in surgically resected T-VEC treated tumors

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Cutaneous
  • Angiosarcoma
  • Skin

Last Updated

July 29, 2019