Clinical Trials /

Study of TVEC in Patients With Cutaneous Squamous Cell Cancer

NCT03714828

Description:

This is single arm a Phase 2, single center study of talimogene laherparepvec (TVEC) to treat low risk cutaneous squamous cell carcinomas (cSCC).

Related Conditions:
  • Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of TVEC in Patients With Cutaneous Squamous Cell Cancer
  • Official Title: A Single Arm Phase 2 Study of Talimogene Laherparepvec in Patients With Cutaneous Squamous Cell Cancer

Clinical Trial IDs

  • ORG STUDY ID: 1807738975
  • SECONDARY ID: 29088
  • NCT ID: NCT03714828

Conditions

  • Squamous Cell Carcinoma
  • Skin Cancer
  • Keratoacanthoma
  • Cutaneous Tumor
  • Skin Cancer, Squamous Cell
  • Lesion Skin

Interventions

DrugSynonymsArms
Injection of TVEC into target lesions - week 1-2Treatment (talimogene laherparepvec)
Injection of TVEC into target lesions 3wks after 1st injectionTreatment (talimogene laherparepvec)
Injection of TVEC into target lesions 2wks after 2nd injectionTreatment (talimogene laherparepvec)
Injection of TVEC into target lesions 2wks after 3rd injectionTreatment (talimogene laherparepvec)

Purpose

This is single arm a Phase 2, single center study of talimogene laherparepvec (TVEC) to treat low risk cutaneous squamous cell carcinomas (cSCC).

Detailed Description

      The purpose of this study is to find out more about talimogene laherparepvec (also known as
      OncoVEXGM-CSF or IMLYGIC®) in people with a healthy immune system with confirmed low-risk
      squamous cell carcinoma. Usually, low-risk SCC is treated with a surgical procedure, but
      surgery can be challenging when patients have: multiple SCCs on their body, when the SCC is
      on a challenging place on the body to remove or when patients are older or have diseases that
      place them at risk for surgery related complications. Immune therapy is a treatment that uses
      certain parts of a person's immune system to fight disease. Immune therapy is a proven
      therapeutic approach in many cancers, including melanoma, another type of skin cancer.

      Talimogene laherparepvec (TVEC) is made from a modified herpes simplex virus type 1 (HSV-1,
      the "cold sore" virus). The virus' genes were modified in a laboratory so that it produces a
      protein called human granulocyte macrophage colony-stimulating factor (GM-CSF), which
      multiplies and grows in tumor cells. Human GM-CSF is normally produced by various cells
      within the body and is used as a medicine to treat patients with white blood cell counts that
      are too low. This modified HSV-1 produces a protein that acts on tumor cells and stimulates
      the immune system. TVEC is administered by injection with a needle directly into one or more
      tumors and works by directly destroying cancer cells and enhancing immune response to destroy
      cancer cells.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (talimogene laherparepvec)ExperimentalThe subject participation period will be approximately 48 weeks. This will include a screening visit, 4 injection visits and 5 follow up visits. Total length of study/patient is 8.5 to 10.5 months. TVEC will be administered by injection with a needle directly into one or more tumors.
  • Injection of TVEC into target lesions - week 1-2
  • Injection of TVEC into target lesions 3wks after 1st injection
  • Injection of TVEC into target lesions 2wks after 2nd injection
  • Injection of TVEC into target lesions 2wks after 3rd injection

Eligibility Criteria

        Inclusion Criteria:

          1. Able to give informed consent in English or Spanish

          2. Age > 18

          3. Have at least one >0.5 cm to <5.0 cm, histologically confirmed low risk cutaneous SCC
             (including kerathoacanthomas)

               -  Size >0.5 cm on trunk or extremities (excluding face, neck feet, nail units, and
                  ankles)

               -  Clinically consistent with primary tumors.

               -  Lesion considered unresectable (as defined in Section 1.2)

               -  Recurrent lesions will be considered eligible if additional inclusion criteria
                  are met.

               -  No immunosuppression

               -  Not a site of previous radiation therapy or chronic significant inflammation

               -  Fast growing lesions (doubling in size over a 4 week period of time) will be
                  included if they are clinically suggestive of cSCC of the keratoacanthoma type.

               -  Well or moderately differentiated tumor as confirmed by skin biopsy

               -  Depth less than 2 mm (for non KA type cSCC )

               -  No perineural or vascular involvement in preliminary biopsy.

          4. Partial biopsy of squamous cell skin cancer identified as a target lesion(s) to
             determine the histological differentiation of the tumor or other adverse histological
             features

          5. In patients with multiple lesions, up to 3 lesions in a similar anatomical site,
             (trunk, limbs etc) that is at least 10 cm apart can be selected.

          6. Maximum of 5 lesions per patient can be selected for treatment

          7. Adequate organ function determined within 28 days prior to enrollment, defined as
             follows:

          8. Hematology:

               -  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)

          9. 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 within
             normal limits. Creatinine clearance should be determined per institutional standard)

         10. Hepatic

               -  Serum bilirubin ≤ 1.5 x ULN

               -  Aspartate aminotransferase (AST) ≤ 2.5 x ULN 23 | Page Version 6-26-2018

               -  Alanine aminotransferase (ALT) ≤ 2.5 x ULN

         11. 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.

         12. Female subject 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:

          1. Any patient with diagnosis of invasive cancer in the last 3 years with the exception
             of stage I and II melanoma, cutaneous BCC and SCCs will be excluded.

          2. Subjects on acitretin, capecitabine, topical chemotherapies or treatments.

          3. History or evidence of symptomatic autoimmune disease (eg, pneumonitis,
             glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
             that has required systemic treatment (ie, use of corticosteroids, immunosuppressive
             drugs or biological agents used for treatment of autoimmune diseases) in past 2 months
             prior to enrollment. Replacement therapy (eg, thyroxine for hypothyroidism, insulin
             for diabetes or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic treatment for autoimmune
             disease.

          4. Evidence of clinically significant immunosuppression such as the following:

               -  Primary immunodeficiency state such as Severe Combined Immuno deficiency Disease

               -  Acquired immunodeficiency syndrome

               -  Concurrent opportunistic infection

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

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

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

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

          8. Prior therapy with tumor vaccine

          9. Received live vaccine within 28 days prior to enrollment. 24 | Page Version 6-26-2018

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

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

         12. Known to have acute or chronic active hepatitis B infection

         13. Known to have acute or chronic active hepatitis C infection

         14. History of other malignancy within the past 3 years with the following exceptions:

               -  adequately treated mucosa associated lymphoid tissue (MALT) tumor

               -  malignancy treated with curative intent and with no known active disease present
                  for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the
                  treating physician

               -  adequately treated non-melanoma skin cancer, lentigo maligna, stage I or II
                  cutaneous melanoma, without evidence of disease.

               -  adequately treated cervical carcinoma in situ without evidence of disease

               -  adequately treated breast ductal carcinoma in situ without evidence of disease

               -  prostatic intraepithelial neoplasia without evidence of prostate cancer

               -  adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
                  situ

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

         16. 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

         17. 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. (Note: Women not of childbearing potential are
             defined as: Any female who is post-menopausal [age > 55 years with cessation of menses
             for 12 or more months or less than 55 years but not spontaneous menses for at least 2
             years or less than 55 years and spontaneous menses within the past 1 year, but
             currently amenorrheic (eg, spontaneous or secondary to hysterectomy), and with
             postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating
             hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according
             to the definition of "postmenopausal range" for the laboratory involved] or who have
             had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). 25 | Page
             Version 6-26-2018

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

         19. Subject who is 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 children under the age of 1 year, 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:8.5-10.5 months
Safety Issue:
Description:The primary end point is to evaluate the overall response rate (ORR) defined as proportion of subjects who achieved complete response (CR) and partial response (PR) in the cSCC Target injected lesions (TILs).

Secondary Outcome Measures

Measure:Number of participants with events requiring the discontinuation of study drug
Time Frame:8.5-10.5 months
Safety Issue:
Description:1. Number of participants with events requiring the discontinuation of study drug 75% or greater number of Target injection lesions (TILs) meeting criteria for withdrawal. Identification of high-risk features in one or more TILs during study participation. Persistent discomfort (consecutive weeks of lesion pain, burning, or itching of Grade 2 or more).
Measure:Time of response.
Time Frame:8.5-10.5 months
Safety Issue:
Description:To measure time of response in cSCC TILs.
Measure:Duration of overall response.
Time Frame:8.5-10.5 months
Safety Issue:
Description:To measure the duration of overall response (DOR) of TILs.
Measure:Assess durable response.
Time Frame:8.5-10.5 months
Safety Issue:
Description:Assess durable response rate (DRR) of TILs.
Measure:Time to progression.
Time Frame:8.5-10.5 months
Safety Issue:
Description:To measure the time to progression (TTP) of TILs
Measure:Overall response rate by ultrasound.
Time Frame:8.5-10.5 months
Safety Issue:
Description:Overall response rate (ORR) (CR+PR) assessed by imaging technique (high frequency ultrasound).
Measure:Overall clinical response rate - targeted lesions.
Time Frame:8.5-10.5 months
Safety Issue:
Description:Overall clinical response rate (CR+PR) of individual TILs with talimogene laherparepvec (not as overall subject response).
Measure:Overall clinical response rate - non-injected lesion(s).
Time Frame:8.5-10.5 months
Safety Issue:
Description:Overall clinical response rate (CR+PR) in cSCC Target non-injected lesion(s) (TNILs).
Measure:Number of safety adverse events (SAE) as assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0
Time Frame:8.5-10.5 months
Safety Issue:
Description:1. Number of safety adverse events (SAE) as assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 a. Clinically significant laboratory values i. Clinically significant laboratory values are based on participant condition and side effect. These will vary and will be determined by the clinical judgement of the research healthcare provider. Note: laboratory values will be collected for initial participant screening and side effects only, no other clinical laboratory values are scheduled in this protocol.
Measure:Number of adverse effects to tumors according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0
Time Frame:8.5-10.5 months
Safety Issue:
Description:Local effects on the tumor as assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 Pain Inflammation Ulceration

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Arizona

Trial Keywords

  • Skin cancer
  • Squamous cell
  • Squamous Cell Carcinoma
  • Skin lesion
  • Keratoacanthoma
  • talimogene laherparepvec

Last Updated

November 18, 2019