E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Central Nervous System (CNS) Tumors |
|
E.1.1.1 | Medical condition in easily understood language |
Tumors that can be injected and do not occur in the brain or spinal cord |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the safety and tolerability of talimogene laherparepvec, as assessed by incidence of dose-limiting toxicities (DLT), in pediatric subjects with advanced non central nervous system (CNS) tumors that are amenable to direct injection. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the anti-tumor activity of talimogene laherparepvec, as assessed by overall response rate (ORR), duration of response (DOR), time to response (TTR), time to progression (TTP), progression-free survival (PFS) using immune-related response criteria simulating Response Evaluation Criteria in Solid Tumor (RECIST 1.1) (modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors [irRC-RECIST]), and overall survival (OS).
• To evaluate the association between granulocyte macrophage colony-stimulating factor (GM-CSF) receptors/subunits in archival tumor tissue and clinical outcomes (safety endpoints and efficacy endpoints such as ORR, DOR, TTR, TTP, PFS, and OS). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects must be 0 to < 18 years of age at the time of informed consent/assent.
• Subjects must have local HSV-1 serostatus with measurable or non-measurable disease.
• Subject must have histologically or cytologically confirmed non-CNS solid tumor that recurred after standard therapy (or for which there is no standard therapy).
• The subject must be a candidate for intralesional therapy and have Karnofsky performance status of ≥ 70% for subjects 12 to < 18 years of age or Lansky play scale of ≤ 70% for children 0 to < 12 years of age.
• Subjects must have a life expectancy of > 4 months from date of enrollment and adequate organ function.
• Female subjects of childbearing potential must have a negative pregnancy test.
|
|
E.4 | Principal exclusion criteria |
• Diagnosis of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, or other hematologic malignancy
• Radiotherapy to the bone marrow within a period of time (see definition in protocol)
• Primary ocular or mucosal melanoma
• History or evidence of giant congenital melanocytic nevi, dysplastic nevis syndrome or xeroderma pigmentosum
• History of other malignancy within the past 5 years (see protocol for exception)
• History or evidence of active autoimmune disease that requires systemic treatment (see protocol for description)
• Evidence of clinically significant immunosuppression (see protocol for examples)
• Active herpetic skin lesions or prior complications of herpetic infection
• Prior treatment with talimogene laherparepvec or any other oncolytic virus or with a tumor vaccine
• Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
• Prior chemotherapy, radiotherapy, or biological cancer therapy (see definition in protocol)
• Currently receiving or recently received treatment in another investigational device or drug study (see definition in protocol).
• Major surgery ≤ 28 days prior to enrollment
• 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 (see definition in protocol)
• 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 to talimogene 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.
• 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
• 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 (see protocol definition)
• 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 (see protocol definition)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary analysis will occur when the last DLT evaluable subject is enrolled and completes the DLT evaluation period. |
|
E.5.2 | Secondary end point(s) |
ORR, DOR, TTR, TTP, PFS, and OS will be summarized in the overall population |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Asessed during the Primary Analysis and updated during the Final Analysis |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Switzerland |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The time when the last subject is assessed or receives an intervention for evaluation in the study. The end of study will occur when the last subject discontinues talimogene laherparepvec and has had the opportunity to complete both the safety follow-up visit and the long-term follow-up. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |