Melanoma stage IIIB-IVM1a
Conditions
Interventions
Trade Name: IMLYGIC
Product Name: Talimogene Laherparepvec
Product Code: AMG 678
Pharmaceutical Form: Solution for solution for injection
INN or Proposed INN: Talimogene Laherparepvec
Current Sponsor
Sponsors
Fundació Clínic per a la Recerca Biomèdica
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Subject has provided informed consent prior to initiation of any study-specific activities/procedures -Male or female age = 18 years. -Histologically confirmed diagnosis of malignant melanoma. -Subjects with unresected stage IIIB to IVM1a melanoma -Candidate for intralesional therapy defined as: - at least 1 injectable cutaneous, subcutaneous or nodal melanoma lesion = 10 mm in longest diameter or, multiple injectable melanoma lesions which in aggregate have a longest diameter of = 10mm and measurable by sonography and positive Doppler signal. -Measurable disease defined as one or more of the following: - at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the greatest diameter is = 10 mm as measured by contrast enhanced or spiral computed tomography (CT) scan for nodal/soft tissue disease(including lymph nodes) - at least 1 = 10 mm superficial cutaneous or subcutaneous melanoma lesion as measured by calipers - at least 1 = 10 mm superficial cutaneous or subcutaneous melanoma lesion as measured by ultrasound - multiple superficial melanoma lesions which in aggregate have a total diameter of = 10mm - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Serum LDH levels = upper limit of normal (ULN) within 28 days prior to enrollment. - Adequate organ function determined within 28 days prior to enrollment, defined as: - Absolute neutrophil count (ANC) = 1,500/mm3 - Platelet count = 100,000/mm3 - Hemoglobin = 8 g/dL without need for hematopoietic growth factor or transfusion support - Serum creatinine = 1.5 x ULN - Serum bilirubin = 1.5 x ULN - Aspartate amino transferase (AST) = 2.5 x ULN - Alanine amino transferase (ALT) = 2.5 x ULN - Alkaline phosphatase = 2.5 x ULN - Serum albumin = 2.5 g/dL - 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: -Primary ocular or mucosal melanoma -Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids >10 mg/day of prednisone or equivalent. The exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability. -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 receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. -Concurrent opportunistic infection. -Patients with allergy to contrast -Subject has known sensitivity to talimogene laherparepvec or any of its components to be administered during dosing. -Patients with a history of any ischemic event will be excluded -Known to have acute or chronic active hepatitis B infection -known to have acute of chronic active hepatitis C infection -known to have human immunodeficiency virus (HIV) infection -Active herpetic skin lesions or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis) -Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, 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. -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. -Subjects 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. -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. Adjuvant hormo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Explore the correlation/predictive role of lesion vascularization (measured by Doppler sonography) and clinical response in subjects with stage IIIB-IVM1a treated with T-VEC.;Secondary Objective: Overall response rates Overall survival Progression free-survival;Primary end point(s): The primary endpoint will be the relationship between the vascularization within the node and skin lesions (quantified by Doppler ultrasound) and the clinical response measured by WHO/RECIST 1.1 criteria to T-VEC treatment from the baseline to the end of the follow-up.;Timepoint(s) of evaluation of this end point: From the baseline to the end of the follow-up. The end of the study trial will be triggered when the last recruited patient completed the final study visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate in patients treated with T-VEC measured by WHO/RECIST criteria Overall survival rate in patients treated with T-VEC measured by WHO/RECIST criteria Progression free-survival in patients treated with T-VEC measured by WHO/RECIST criteria;Timepoint(s) of evaluation of this end point: Overall response rate at the end of treatment. Overall survival rate at the end of follow-up. Progression free-survival at the end of follow-up | — |
Countries
Spain
Contacts
Public ContactPablo Iglesias García
Fundació Clínic per a la Recerca Biomèdica
Outcome results
None listed