Study of Talimogene Laherparepvec In Children With Advanced Non CNS Tumors
Condition: Advanced Non CNS Tumors
MeSH terms: Neoplasms
Intervention: Talimogene Laherparepvec
Intervention description: Talimogene laherparepvec will be administered by intralesional injection only into injectable cutaneous, subcutaneous, nodal tumors, and other non-visceral tumors with or without image ultrasound guidance. The first dose of talimogene laherparepvec will be up to 4.0 mL of 10^6 PFU/mL administered on day 1. The second injection, up to 4.0 mL of 10^8 PFU/mL (or up to 4.0 mL of 10^6 PFU/mL for a dose de-escalated cohort), will be administered 21 (+3) days after the initial injection. All subsequent injections, up to 4.0 mL of 10^8 PFU/mL (or up to 4.0 mL of 10^6 PFU/mL for a dose de-escalated cohort), will be administered every 14 (± 3) days. The treatment cycle interval may be increased due to toxicity.
Intervention MeSH terms: Talimogene laherparepvec
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Approximately 18 to 24 treated pediatric subjects are expected to be enrolled into 2 cohorts stratified by age (permissible based on the incidence of DLTs, a minimum of 6 subjects/cohort and a minimum of 18 subjects total).
Cohort A1 (12 to ≤ 21 years of age)
Cohort B1 (2 to < 12 years of age) Initially, 3 subjects 12 to ≤ 21 years of age are to be enrolled and treated at 100% of the recommended adult dose regimen of talimogene laherparepvec (cohort A1). The dose level review team (DLRT) will review the safety data of the first 3 subjects in the older age cohort A1 to decide if the younger age cohort B1 can be opened for enrollment. If a DLT occurs in the first 3 DLT-evaluable subjects in the older age cohort (A1 or A2), the younger age cohort will not open until a DLT rate < 33% is observed with at least 6 DLT-evaluable subjects in the older age cohort (A1 or A2).
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 2 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Non CNS Tumor

Summary:

      This is a phase 1 study to evaluate the safety of intralesional talimogene laherparepvec
      administration in pediatric subjects with advanced non-CNS tumors that are amenable to direct
      injection
    

Eligibility criteria:

        Inclusion Criteria

          -  Subject's legally acceptable representative has provided informed consent/assent when
             the subject is legally too young to provide informed consent/assent and the subject
             has provided written assent based on local regulations and/or guidelines prior to any
             study-specific activities/procedures being initiated.

          -  Should be willing to submit local HSV-1 serostatus within 28 days prior to enrollment.

          -  Subject must be a candidate for intralesional injection, defined as one or more of the
             following:

               -  at least 1 injectable lesion ≥ 10 mm in longest diameter

               -  multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm

          -  Life expectancy > 4 months from the date of enrollment.

          -  Male or female subjects 2 to ≤ 21 years of age at the time of informed consent/assent.

          -  Histologically or cytologically confirmed non-CNS solid tumor that recurred after
             standard/frontline therapy, or for which there is no standard/frontline therapy
             available.

          -  Presence of measurable or non-measurable lesions as defined by irRC-RECIST

          -  Performance status as per protocol

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy test within 72 hours prior to dosing.

          -  Adequate organ function as defined in protocol

             •Exclusion Criteria

          -  Diagnosis of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, or other hematologic
             malignancy.

          -  Radiotherapy to the bone marrow within 6 weeks prior to enrollment OR within 3 months
             prior to enrollment if prior radiotherapy to the craniospinal axis or to at least 60%
             of the pelvis was received; within 2 weeks prior to enrollment if local palliative
             radiotherapy was received.

          -  Primary ocular or mucosal melanoma.

          -  History of other malignancy within the past 5 years with the following exception:

             • malignancy treated with curative intent and with no known active disease present and
             has not received chemotherapy for > 5 years before enrolment and felt to be at low
             risk for recurrence by the treating physician.

          -  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.

          -  Active herpetic skin lesions or prior complications of herpetic infection (eg,
             herpetic keratitis or encephalitis).

          -  Prior treatment with talimogene laherparepvec or any other oncolytic virus.

          -  Prior treatment with a tumor vaccine.

          -  Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir),
             other than intermittent topical use.

          -  Expected to require other cancer therapy while on study with the exception of local
             palliative radiation treatment.

          -  Has acute or chronic active hepatitis B virus or hepatitis C virus infection or
             received treatment with nucleotide analogs such as those used in the treatment of
             hepatitis B virus (eg, lamivudine, adefovir, tenofovir, telbivudine, and entecavir),
             ribavirin, or interferon alpha within 12 weeks of initiation of study treatment.

          -  Known or suspected human immunodeficiency virus (HIV) infection.

          -  Received live vaccine within 28 days prior to enrollment.

          -  No antiplatelet or anticoagulation medications allowed within 7 days prior
             totalimogene laherparepvec injection except low-dose heparin needed to maintain venous
             catheter patency.

          -  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. Note: Acceptable methods of effective contraception
             are defined in the informed consent/assent form. Where required by local laws and
             regulations, additional country-specific contraception requirements may be outlined in
             a country-specific protocol supplement at the end of the Appendix Section of protocol.

          -  Subject has known sensitivity to any of the products or components to be administered
             during dosing.

          -  Subject likely to not be available to complete all protocol-required study visits or
             procedures, and/or to comply with all required study procedures to the best of the
             subject and investigator's knowledge.

          -  History or evidence of any psychiatric disorder, substance abuse or any other
             clinically significant disorder, condition or disease (with the exception of those
             outlined above) that, in the opinion of the investigator or Amgen physician, if
             consulted, would pose a risk to subject safety or interfere with the study evaluation,
             procedures or completion.

          -  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
             (immunosuppressed individuals, HIV-positive individuals, pregnant women, or children
             under the age of 1 year) during talimogene laherparepvec treatment and through 28 days
             after the last dose of talimogene laherparepvec.

          -  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 prior to enrollment),
                  including oral steroid doses (with the exception of maintenance physiologic
                  replacement). Subjects who require intermittent use of steroids for inhalation or
                  local steroid injection will not be excluded from the study

               -  less than 6 months from autologous bone marrow transplant or stem cell infusion

               -  history of allogeneic bone marrow transplant

          -  History or evidence of xeroderma pigmentosum.

          -  Sexually active subjects and their partners unwilling to use a 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. For those with latex
             allergies, polyurethane condoms may be used.

          -  Prior chemotherapy, treatment dose radiotherapy, or biological cancer therapy within
             14 days prior to enrollment or has not recovered to Common Terminology Criteria for
             Adverse Events version 4.0 (CTCAE) grade 1 or better from adverse event due to cancer
             therapy administered more than 14 days prior to enrollment.

          -  CNS tumor or clinically active brain metastases (patient with a history of treated
             brain metastases are eligible if there is radiographic evidence of improvement upon
             the completion of CNS-directed therapy and no evidence of interim progression between
             the completion of CNS-directed therapy and the screening radiographic study).

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 14 days since ending treatment on another investigational device or drug
             study(ies) or has not recovered to CTCAE version 4.0 grade 1 or better from adverse
             event due to other investigational device or drug study administered more than 14 days
             prior to enrollment. Other investigational procedures while participating in this
             study are excluded.

          -  Major surgery ≤ 14 days prior to enrollment or has not recovered to CTCAE version 4.0
             grade 1 or better from adverse event due to surgery performed more than 14 days prior
             to enrollment.