Unresected stage IIIB to IVM1c melanoma
Conditions
Sponsors
Amgen Inc.
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 at the time of informed consent - Histologically confirmed diagnosis of melanoma - Subject with unresected stage IIIB to IVM1c melanoma for whom surgery is not recommended - Subject who is treatment naïve: must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IVM1c melanoma - subjects who received prior adjuvant therapy for melanoma may be eligible as long as prior adjuvant therapy was completed at least 6 months prior to enrollment - Candidate for intralesional therapy (ie, disease is appropriate for direct injection or through the use of ultrasound guidance) defined as one of the following: -at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion = 10 mm in longest diameter, or - multiple injectable melanoma lesions that in aggregate have a longest diameter of = 10 mm - 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, magnetic resonance imaging (MRI), or ultrasound for nodal/soft tissue disease (including lymph nodes) - at least 1 = 10 mm superficial cutaneous or subcutaneous melanoma lesion as measured by calipers - multiple superficial melanoma lesions which in aggregate have a total diameter of = 10 mm - Serum lactate dehydrogenase (LDH) levels = 1.5 X upper limit of normal (ULN) within 28 days prior to enrollment - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix E) - Adequate organ function determined within 28 days prior to enrollment, defined as follows: - absolute neutrophil count = 1500/mm3 - platelet count = 75,000/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 - prothrombin time (PT) = 1.5 x ULN (or international normalization ratio [INR] = 1.3)* - partial thromboplastin time (PTT) = 1.5 x ULN 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 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: - Clinically active cerebral metastases. Subjects with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy (including Gamma Knife) or craniotomy, with no evidence of progression and have not required steroids for at least two months prior to enrollment. - Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For subjects with 3 visceral metastases, no lesion > 3 cm and liver lesions must be stable for at least 1 month prior to enrollment. - Bone metastases - Primary ocular or mucosal melanoma - History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease - 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 - 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 - Any nononcology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period - Currently receiving treatment with another investigational device or drug study, or less than 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 - Known to have acute or chronic active hepatitis C infection - Known to have human immunodeficiency virus infection - History of other malignancy within the past 3 years with the following exceptions: - 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 or lentigo maligna 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 - 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’s and investigator’s knowledge - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion - Subject previously has entered this study - Female subject is pregnant or breast-fe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the correlation between a baseline immunoprofile (ie, intratumoral CD8+ cell density) and objective response rate (ORR) in subjects with unresected stage IIIB to IVM1c melanoma treated with talimogene laherparepvec.;Secondary Objective: - to explore the correlation between a baseline immunoprofile (ie, intratumoral CD8+ cell density) and durable response rate (DRR), duration of response (DOR), and changes in tumor burden - to explore the correlation between changes in an immunoprofile intratumoral CD8+ cell density during treatment (in injected and uninjected lesions) and ORR, DRR, DOR, and changes in tumor burden - to evaluate ORR, DOR, time to treatment failure (TTF), DRR, OS, and change in tumor burden during treatment - to evaluate the safety and tolerability of talimogene laherparepvec ;Primary end point(s): The primary endpoint of the study is the correlation between baseline intratumoral CD8+ cell density and objective response rate (ORR). ;Timepoint(s) of evaluation of this end point: The timing of the primary analysis will be when all subjects have had the opportunity to complete 12 months of treatment of talimogene laherparepvec. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Multiple biomarkers will be examined to assess the correlation between their baseline value and DRR, DOR, and changes in tumor burden as well as the changes in their value during treatment with ORR, DRR, DOR, changes in tumor burden. Subject incidence rates of treatment-emergent adverse events (including all adverse events, grade = 3 adverse events, serious adverse events, adverse events of interest and events requiring the discontinuation of study drug,and local effects on the tumor [ie, pain, inflammation and ulceration]) will be summarized. Clinically significant laboratory changes and clinically significant changes in vital signs will be summarized with descriptive statistics. Summary statistics will also be provided for concomitant medications, dose delay, study drug discontinuation, overall exposure, and changes in ECOG performance status.;Timepoint(s) of evaluation of this end point: The timing of the primary analysis will be when all subjects have had the opportunity to complete 12 months of treatment of talimogene laherparepvec. | — |
Countries
Austria, Belgium, Germany, Greece, Hungary, Italy, Netherlands, Poland, Spain, United States
Contacts
Public ContactIHQ medical Info-Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed