Ipilimumab With or Without Talimogene Laherparepvec in Unresected Melanoma
- Conditions
- nresected, Stage IIIB-IV MelanomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-000307-32-DE
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 218
4.1.1 Subject has provided informed consent
4.1.2 Histologically confirmed diagnosis of malignant melanoma
4.1.3 Stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c disease that is not suitable for surgical resection
4.1.4 Phase 1b: Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IV melanoma. Note: Subjects who received prior adjuvant therapy for melanoma will not be excluded. However, if the subject received adjuvant therapy, the subject must have completed therapy at least 6 months prior to enrollment. No prior talimogene laherparepvec, ipilimumab, other CTLA-4 inhibitors , programmed death-1 (PD-1) inhibitors, or tumor vaccine is allowed, even if given in the adjuvant setting.
4.1.5 Phase 2:
• Either treatment naïve or received only one line of systemic
anticancer therapy if BRAF wild-type or up to two lines of systemic
anticancer therapy including one BRAF inhibitor-containing regimen
if BRAF mutant. Treatments given in an adjuvant setting (eg, interferon, radiotherapy, isolated limb perfusion, or investigational agents) are not considered as prior lines of therapy.
No prior talimogene laherparepvec, other oncolytic virus therapies,
or tumor vaccines are allowed, even if given in the adjuvant setting.
• Subjects treated with prior ipilimumab must have had PR, CR, or at
least 6 months of stable disease followed by disease progression
• Subjects previously treated with anti-PD1 or anti-CTLA-4 antibodies
must not have discontinued therapy due to any treatment-related
adverse events including immune-related adverse events. Prior
treatment-related adverse events should also be fully resolved and
not requiring treatment for at least 28 days prior to randomization.
4.1.6 Measurable disease defined as one or both of the following:
• at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the longest diameter is = 10 mm and with perpendicular diameter = 5 mm as measured by
contrast-enhanced or spiral computed tomography (CT) scan for visceral or nodal/soft tissue disease. Lymph nodes must measure > 15 mm in their short axis to be considered measurable by CT scan.
• at least 1 superficial cutaneous or subcutaneous melanoma lesion that can be accurately and serially measured in at least 2 dimensions
and for which the short axis is = 5 mm as measured by calipers
4.1.7 Injectable disease (ie, suitable for direct injection or through the use of ultrasound [US] guidance) defined as follows:
• at least 1 injectable cutaneous, subcutaneous, or nodal melanoma
lesion = 5 mm in longest diameter
4.1.8 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4.1.9 Male or female, age = 18 years
4.1.10 Adequate hematologic, hepatic, renal, and coagulation functions as described in the protocol Section 4.1
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 107
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 111
4.2.1 Primary uveal or mucosal melanoma
4.2.2 History/evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia)
4.2.3 Phase 1b:History/evidence of central nervous system (CNS) metastases
4.2.4 Phase 2: Clinically active cerebral melanoma metastases.Subjects with up to 3 cerebral metastases,&neurological performance status
of 0 may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy,craniotomy,or Gamma knife therapy, with no evidence of progression, and have not required steroids,for at least 2 months prior to enrollment.
4.2.5 History of other malignancy within the past 3yrs with exceptions (details in protocol)
4.2.6 History or evidence of symptomatic autoimmune disease (such as pneumonitis, glomerulonephritis, vasculitis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, scleroderma, or other), or history of autoimmune disease that 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 mellitus) is not considered a form of systemic treatment for autoimmune disease.
4.2.7 Evidence of clinically significant immunosuppression for any reason (see details in protocol)
4.2.8 Active herpetic skin lesions or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis)
4.2.9 Requires intermittent or chronic systemic (intravenous or oral) treatment with antiherpetic drug(eg,acyclovir),other than intermittent topical use 4.2.11 Known HIV disease (if clinically suspected HIV infection,subject requires negative test)
4.2.12 Known acute or chronic hepatitis B or C infection (if clinically suspected hepatitis B or C infection,subject requires negative test. However,if positive results are not indicative of true active/chronic infection,subject may be enrolled/randomized after approval is obtained from Amgen medical monitor).
4.2.13 Female subject is pregnant/breast-feeding/planning to become pregnant during study treatment and through 3mo after last dose of treatment 4.2.14 Female subject of childbearing potential who is unwilling to use acceptable methods of effective contraception during study treatment and through 3mo after last dose of talimogene laherparepvec/ipilimumab,whichever is later.
4.2.15 Male subject who is unwilling to use acceptable method of effective contraception during ipilimumab treatment&through 3 months after the last dose of ipilimumab
4.2.16 Phase 1b: Prior talimogene laherparepvec, ipilimumab,other CTLA-4 inhibitors,PD-1 inhibitors,or tumor vaccine
4.2.17 Phase 2: Prior talimogene laherparepvec,other oncolytic virus therapies,or tumor vaccines
4.2.18 Currently receiving or less than 28days since ending systemic anticancer treatment consisting of chemotherapy,immunotherapy,or targeted therapy for unresected stage IIIB-IV melanoma
4.2.19 Currently receiving treatment in another investigational device or drug study,or less than 30days since ending treatment on another investigational device or drug study(s)
4.2.20 Other investigational procedures while participating in this study are excluded
4.2.21 Has known sensitivity to any of the products or components to be administered during dosing
4.2.22 Previously has entered this study
4.2
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method